2003年, がん研究助成金　　　　　　　　　　　　　　　
日本国

Comparison of busulfan pharmacokinetics between four-times-daily and once-daily administration in pediatric patients: a preliminary prospective observational trial
Atsushi Yamaguchi, Shinsuke Hirabayashi, Kazuko Niki, Keisuke Kagami, Yukayo Terashita, Yuko Cho, Atsushi Manabe, Mitsuru Sugawara, Yoh Takekuma
International Journal of Hematology, Springer Science and Business Media LLC, 2024年12月03日
研究論文（学術雑誌）

Outcomes in children with first-relapsed acute lymphoblastic leukemia in Japan: Results from JCCG Study JPLSG-ALL-R08.
Junko Yamanaka, Chitose Ogawa, Ayumu Arakawa, Takao Deguchi, Toshinori Hori, Nobutaka Kiyokawa, Hideaki Ueki, Masanori Nishi, Shinji Mochizuki, Takuro Nishikawa, Tadashi Kumamoto, Ritsuo Nishiuchi, Atsushi Kikuta, Shohei Yamamoto, Katsuyoshi Koh, Daisuke Hasegawa, Atsushi Ogawa, Kenichiro Watanabe, Atsushi Sato, Akiko M Saito, Tomoyuki Watanabe, Atsushi Manabe, Keizo Horibe, Hiroaki Goto, Hidemi Toyoda
Pediatric blood & cancer, 71, 12, e31319, 2024年12月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/OBJECTIVES: The Berlin-Frankfurt-Münster (BFM)-S classification is a crucial prognostic indicator in children experiencing first-relapsed acute lymphoblastic leukemia (ALL). Early molecular response to therapy, evaluated by measurable/minimal residual disease (MRD), has a significant impact on the survival of patients with childhood ALL. Applying risk stratification based on the BFM-S classification and MRD response after induction, the first nationwide prospective multicenter study, ALL-R08, was conducted in children with first-relapsed ALL in Japan. METHODS: The ALL-R08 study comprised two parts: ALL-R08-I, an observational study aimed at obtaining an overall picture of outcomes in first-relapsed childhood ALL, and ALL-R08-II, a clinical trial for the non-T-ALL S2 risk group. In ALL-R08-II, patients with an MRD level of ≥10-3 at the end of induction therapy were assigned to undergo allogeneic hematopoietic stem cell transplantation (allo-HCT), whereas those with an MRD level less than 10-3 and isolated extramedullary relapse continued to receive chemotherapy. RESULTS: In total, 163 patients were enrolled in the ALL-R08 study, and 82 and 81 patients were enrolled in the ALL-R08-I and the ALL-R08-II, respectively. In ALL-R08-I, the probability of 3-year event-free survival (EFS) for patients with S1, S2, S3, S4, and post-HCT groups was 83% ± 15%, 37% ± 11%, 28% ± 8%, 14% ± 7%, and 0%, respectively. In the ALL-R08-II trial, 3-year EFS in patients with post-induction MRD less than 10-3 and ≥10-3 was 70% ± 9% (n = 27) and 68% ± 8% (n = 31) (p = .591), respectively. CONCLUSIONS: ALL-REZ BFM-type treatment is equally effective for children with first-relapsed ALL treated according to the Japanese frontline protocols and for children with first-relapsed ALL treated according to the BFM-type frontline protocols.

Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG.
Masahiro Ueki, Shinsuke Hirabayashi, Yoshitaka Honda, Shunichiro Takezaki, Hiroki Ohata, Shimaa Said Mohamed Ali Abdrabou, Saori Sawai, Yukayo Terashita, Yuko Cho, Hideki Muramatsu, Kazushi Izawa, Takahiro Yasumi, Yoshiyuki Takahashi, Masafumi Yamada, Atsushi Manabe
Immunological medicine, 1, 8, 2024年11月01日, ［国際誌］
英語, 研究論文（学術雑誌）, X-linked NF-κB essential modulator (NEMO) deficiency is a primary immunodeficiency characterized by combined immunodeficiency and ectodermal dysplasia. Monocytes from the patients demonstrate a severely impaired response to tissue necrosis factor or lipopolysaccharide, whereas hyper-inflammation is found in some patients. Juvenile myelomonocytic leukemia (JMML) is a pediatric malignancy caused by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and aberrant RAS signaling activation. Patients with JMML demonstrate characteristic manifestations such as splenomegaly, monocytosis and the presence of myeloid or erythroid precursors in the peripheral blood. Here, we present the case of a male infant with ectodermal dysplasia, bacterial septicemia, Pneumocystis pneumonia, severe inflammation and transient manifestations mimicking JMML. Genetic analysis revealed a deep intronic germline variant of IKBKG. Full-length IKBKG cDNA and NEMO protein expression were almost inexistent. Peripheral mononuclear cells (PBMCs) from the patient showed increased RAS signaling activation with GM-CSF or Phorbol 12-myristate 13-acetate without the RAS-associated gene variant, although the increased RAS signaling activation in induced-pluripotent stem cell-derived myeloid lineage and bone marrow-derived mesenchymal cells was not evident. The patient with NEMO deficiency demonstrated JMML-like manifestation and severe inflammation. PBMCs of the patient demonstrated increased RAS signaling activation with unknown pathophysiology.

Biologic and clinical analysis of childhood gamma delta T-ALL identifies LMO2/STAG2 rearrangements as extremely high-risk.
Shunsuke Kimura, Chun Shik Park, Lindsey E Montefiori, Ilaria Iacobucci, Petri Polonen, Qingsong Gao, Elizabeth D Arnold, Andishe Attarbaschi, Anthony Brown, Barbara Buldini, Kenneth J Caldwell, Yunchao Chang, Chelsey Chen, Cheng Cheng, Zhongshan Cheng, John Choi, Valentino Conter, Kristine R Crews, Hester A de Groot-Kruseman, Takao Deguchi, Mariko Eguchi, Hannah Elisa Muhle, Sarah Elitzur, Gabriele Escherich, Burgess B Freeman, Zhaohui Gu, Katie Han, Keizo Horibe, Toshihiko Imamura, Sima Jeha, Motohiro Kato, Kean Hui Chiew, Tanya Khan, Michal Kicinski, Stefan Kohrer, Steven M Kornblau, Rishi S Kotecha, Chi-Kong Li, Yen-Chun Liu, Franco Locatelli, Selina M Luger, Elisabeth M Paietta, Atsushi Manabe, Hanne Vibeke Marquart, Riccardo Masetti, Mellissa Maybury, Pauline Mazilier, Jules P P Meijerink, Sharnise Mitchell, Takako Miyamura, Andrew S Moore, Koichi Oshima, Katarzyna Pawinska-Wasikowska, Rob Pieters, Mollie S Prater, Shondra M Pruett-Miller, Ching-Hon Pui, Chunxu Qu, Michaela Reiterova, Noemi Reyes, Kathryn G Roberts, Jacob M Rowe, Atsushi Sato, Kjeld Schmiegelow, Martin Schrappe, Shuhong Shen, Szymon Skoczen, Orietta Spinelli, Jan Stary, Michael Svaton, Masatoshi Takagi, Junko Takita, Yanjing Tang, David T Teachey, Paul G Thomas, Daisuke Tomizawa, Jan Trka, Elena Varotto, Tiffaney L Vincent, Jun J Yang, Allen Ej Yeoh, Yinmei Zhou, Martin Zimmermann, Hiroto Inaba, Charles G Mullighan
Cancer discovery, 2024年06月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Acute lymphoblastic leukemia expressing the gamma delta T cell receptor (yo T-ALL) is a poorly understood disease. We studied 200 children with yo T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. yo T-ALL diagnosed in children under three years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by Poly(ADP-ribose) polymerase (PARP) inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric yo T-ALL.

Identification of Prostaglandin I2 Synthase Rare Variants in Patients With Williams Syndrome and Severe Peripheral Pulmonary Stenosis.
Ayako Chida-Nagai, Hiroyuki Akagawa, Saori Sawai, Yue-Jiao Ma, Satoshi Yakuwa, Jun Muneuchi, Kazushi Yasuda, Hirokuni Yamazawa, Toshiyuki Yamamoto, Emi Takakuwa, Utano Tomaru, Yoshiyuki Furutani, Tatsuya Kato, Gen Harada, Kei Inai, Toshio Nakanishi, Atsushi Manabe, Atsuhito Takeda, Zhi-Cheng Jing
Journal of the American Heart Association, e032872, 2024年04月19日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Peripheral pulmonary stenosis (PPS) is a condition characterized by the narrowing of the pulmonary arteries, which impairs blood flow to the lung. The mechanisms underlying PPS pathogenesis remain unclear. Thus, the aim of this study was to investigate the genetic background of patients with severe PPS to elucidate the pathogenesis of this condition. METHODS AND RESULTS: We performed genetic testing and functional analyses on a pediatric patient with PPS and Williams syndrome (WS), followed by genetic testing on 12 patients with WS and mild-to-severe PPS, 50 patients with WS but not PPS, and 21 patients with severe PPS but not WS. Whole-exome sequencing identified a rare PTGIS nonsense variant (p.E314X) in a patient with WS and severe PPS. Prostaglandin I2 synthase (PTGIS) expression was significantly downregulated and cell proliferation and migration rates were significantly increased in cells transfected with the PTGIS p.E314X variant-encoding construct when compared with that in cells transfected with the wild-type PTGIS-encoding construct. p.E314X reduced the tube formation ability in human pulmonary artery endothelial cells and caspase 3/7 activity in both human pulmonary artery endothelial cells and human pulmonary artery smooth muscle cells. Compared with healthy controls, patients with PPS exhibited downregulated pulmonary artery endothelial prostaglandin I2 synthase levels and urinary prostaglandin I metabolite levels. We identified another PTGIS rare splice-site variant (c.1358+2T>C) in another pediatric patient with WS and severe PPS. CONCLUSIONS: In total, 2 rare nonsense/splice-site PTGIS variants were identified in 2 pediatric patients with WS and severe PPS. PTGIS variants may be involved in PPS pathogenesis, and PTGIS represents an effective therapeutic target.

TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia.
Hideaki Ueki, Chitose Ogawa, Hiroaki Goto, Masanori Nishi, Junko Yamanaka, Shinji Mochizuki, Takuro Nishikawa, Tadashi Kumamoto, Ritsuo Nishiuchi, Atsushi Kikuta, Shohei Yamamoto, Shunji Igarashi, Atsushi Sato, Toshinori Hori, Akiko M Saito, Tomoyuki Watanabe, Takao Deguchi, Atsushi Manabe, Keizo Horibe, Hidemi Toyoda
International journal of hematology, 2024年01月25日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.

Allogeneic Hematopoietic Cell Transplantation for Juvenile Myelomonocytic Leukemia with a Busulfan, Fludarabine, and Melphalan Regimen: JPLSG JMML-11.
Kazuo Sakashita, Nao Yoshida, Hideki Muramatsu, Yoshitoshi Ohtsuka, Kenichiro Watanabe, Miharu Yabe, Harumi Kakuda, Yuko Honda, Tomoyuki Watanabe, Masami Haba, Shigeru Ohmori, Kazuyuki Matsuda, Yuki Yuza, Akiko Saito, Keizo Horibe, Souichi Adachi, Atsushi Manabe
Transplantation and cellular therapy, 30, 1, 105.e1-105.e10, 2024年01月, ［国際誌］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia (JMML), which is classified as a myelodysplastic/myeloproliferative neoplasm, is a rare hematologic malignancy of childhood. Most patients with JMML require allogeneic hematopoietic cell transplantation (HCT) as a curative therapy. A Japanese retrospective analysis demonstrated favorable outcomes for a busulfan (BU) + fludarabine (FLU) + melphalan (MEL) regimen, with an overall survival (OS) of 72% and an event-free survival (EFS) of 53%. To further validate the efficacy and safety of this regimen, the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) conducted a nationwide prospective study, JMML-11. Between July 2011 and June 2017, 28 patients with newly diagnosed JMML were enrolled in JMML11. Low-dose chemotherapy for tumor control before HCT was recommended, and patients treated with AML-type chemotherapy and azacitidine were excluded. The conditioning regimen comprised i.v. BU, 16 doses administered every 6 h, with dose adjustment based on pharmacokinetic (PK) studies on days -11 to -8; FLU, 30 mg/m2/day or 1 mg/kg/day for patients <10 kg or age <1 year on days -7 to -4; and MEL, 90 mg/m2/day or 3 mg/kg/day for patients <10 kg or <1 year on days -3 to -2. The donor was selected by the physician in charge. A family donor was available for 7 patients (3 HLA-matched siblings, 3 HLA-1-antigen mismatched parents, and 1 haploidentical father). Overall, 21 patients received grafts from unrelated donors, including 8 HLA-matched donors and 13 HLA-mismatched donors. The graft source was related bone marrow (BM) for 7 patients, unrelated BM for 14 patients, and unrelated cord blood for 7 patients. Neutrophil engraftment was achieved in 21 of 28 patients (75%), with a median of 20.5 days (range, 11 to 39 days) after transplantation. The 3-year OS, 3-year EFS, 3-year relapse rate, and 3-year transplantation-related mortality were 63% (95% confidence interval [CI], 42% to 78%), 52% (95% CI, 32% to 69%), 18% (95% CI, 6% to 34%), and 21% (95% CI, 9% to 38%), respectively. WBC count before the conditioning regimen (≥7.0 × 109/L) was significantly associated with inferior EFS and OS. Body surface area ≥.5 m2, spleen size <4 cm before conditioning, and HLA-matched unrelated BM donors were significantly associated with better OS. Adverse effects related to the conditioning regimen included febrile neutropenia (86%), diarrhea (39%), hypoxemia (21%), and mucositis (18%). BU-associated toxicity, including sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA), occurred in 7 patients (25%; SOS, n = 6; TMA, n = 2). Retrospective analysis of PK data after the first BU dose in 23 patients, including 6 with SOS and 17 without SOS, did not show significant differences between groups. The JMML-11 study confirms the positive results of previous retrospective analyses. BU+FLU+MEL might become a standard conditioning regimen for patients with JMML.

Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function.
Yuki Ueda, Kiyoshi Egawa, Kentaro Kawamura, Noriki Ochi, Takeru Goto, Shuhei Kimura, Masashi Narugami, Sachiko Nakakubo, Midori Nakajima, Atsushi Manabe, Hideaki Shiraishi
Brain & development, 2023年12月15日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established. METHODS: We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers' evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes. RESULTS: All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration. CONCLUSIONS: The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.

Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.
Shunsuke Kimura, Petri Polonen, Lindsey Montefiori, Chun Shik Park, Ilaria Iacobucci, Allen Ej Yeoh, Andishe Attarbaschi, Andrew S Moore, Anthony Brown, Atsushi Manabe, Barbara Buldini, Burgess B Freeman, Chelsey Chen, Cheng Cheng, Chiew Kean Hui, Chi-Kong Li, Ching-Hon Pui, Chunxu Qu, Daisuke Tomizawa, David T Teachey, Elena Varotto, Elisabeth M Paietta, Elizabeth D Arnold, Franco Locatelli, Gabriele Escherich, Hannah Elisa Muhle, Hanne Vibeke Marquart, Hester A de Groot-Kruseman, Jacob M Rowe, Jan Stary, Jan Trka, John Kim Choi, Jules P P Meijerink, Jun J Yang, Junko Takita, Katarzyna Pawinska-Wasikowska, Kathryn G Roberts, Katie Han, Kenneth J Caldwell, Kjeld Schmiegelow, Kristine R Crews, Mariko Eguchi, Martin Schrappe, Martin Zimmerman, Masatoshi Takagi, Mellissa Maybury, Michael Svaton, Michaela Reiterova, Michal Kicinski, Mollie S Prater, Motohiro Kato, Noemi Reyes, Orietta Spinelli, Paul Thomas, Pauline Mazilier, Qingsong Gao, Riccardo Masetti, Rishi S Kotecha, Rob Pieters, Sarah Elitzur, Selina M Luger, Sharnise Mitchell, Shondra M Pruett-Miller, Shuhong Shen, Sima Jeha, Stefan Köhrer, Steven M Kornblau, Szymon Skoczeń, Takako Miyamura, Tiffaney L Vincent, Toshihiko Imamura, Valentino Conter, Yanjing Tang, Yen-Chun Liu, Yunchao Chang, Zhaohui Gu, Zhongshan Cheng, Zhou Yinmei, Hiroto Inaba, Charles G Mullighan
medRxiv : the preprint server for health sciences, 2023年11月08日, ［国際誌］
英語, PURPOSE: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease. METHODS: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing. Experimental modeling was used to examine the mechanistic impacts of genomic alterations. Therapeutic vulnerabilities were identified by high throughput drug screening of cell lines and xenografts. RESULTS: γδ T-ALL in children under three was extremely high-risk with 5-year event-free survival (33% v. 70% [age 3-<10] and 73% [age ≥10], P =9.5 x 10 -5 ) and 5-year overall survival (49% v. 78% [age 3-<10] and 81% [age ≥10], P =0.002), differences not observed in non-γδ T-ALL. γδ T-ALL in this age group was enriched for genomic alterations activating LMO2 activation and inactivating STAG2 inactivation ( STAG2/LMO2 ). Mechanistically, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping resulting in deregulation of gene expression associated with T-cell differentiation. Drug screening showed resistance to prednisolone, consistent with clinical slow treatment response, but identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which was efficaciously targeted by Poly(ADP-ribose) polymerase (PARP) inhibition, with synergism with HDAC inhibitors. Ex-vivo drug screening on PDX cells validated the efficacy of PARP inhibitors as well as other potential targets including nelarabine. CONCLUSION: γδ T-ALL in children under the age of three is extremely high-risk and enriched for STAG2/LMO2 ALL. STAG2 loss perturbs chromatin conformation and differentiation, and STAG2/LMO2 ALL is sensitive to PARP inhibition. These data provide a diagnostic and therapeutic framework for pediatric γδ T-ALL. SUPPORT: The authors are supported by the American and Lebanese Syrian Associated Charities of St Jude Children's Research Hospital, NCI grants R35 CA197695, P50 CA021765 (C.G.M.), the Henry Schueler 41&9 Foundation (C.G.M.), and a St. Baldrick's Foundation Robert J. Arceci Innovation Award (C.G.M.), Gabriella Miller Kids First X01HD100702 (D.T.T and C.G.M.) and R03CA256550 (D.T.T. and C.G.M.), F32 5F32CA254140 (L.M.), and a Garwood Postdoctoral Fellowship of the Hematological Malignancies Program of the St Jude Children's Research Hospital Comprehensive Cancer Center (S.K.). This project was supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820, UG1CA189859, U24CA114766, U10CA180899, U10CA180866 and U24CA196173. DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agencies were not directly involved in the design of the study, gathering, analysis and interpretation of the data, writing of the manuscript, or decision to submit the manuscript for publication.

Use of lacosamide for focal epilepsy in a child with kidney failure undergoing peritoneal dialysis.
Yuki Ueda, Ayako Furugen, Masaki Kobayashi, Yasuyuki Sato, Yasuhiro Ueda, Asako Hayashi, Takeru Goto, Shuhei Kimura, Masashi Narugami, Sachiko Nakakubo, Midori Nakajima, Kiyoshi Egawa, Takayuki Okamoto, Atsushi Manabe, Hideaki Shiraishi
Brain & development, 2023年10月30日, ［国際誌］
英語, BACKGROUND: Lacosamide (LCM) has become commonly used for focal onset seizures due to its high tolerability and low drug interactions. Unlike patients on hemodialysis (HD), pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis (PD) are scant. CASE REPORT: A 2-year-old girl with end-stage kidney disease undergoing PD suffered prolonged focal onset seizures. The patient had congenital anomalies of the kidney and urinary tract associated with branchio-oto-renal syndrome due to an EYA1 gene mutation. She also had neurological sequelae from post-resuscitation encephalopathy at the age of one month. Antiseizure medication with few drug interactions, less impact on the neurodevelopmental state and possibility of intravenous administration was preferred. LCM met those criteria and was carefully administered. Although the patient had recurrent prolonged seizures during the titration periods, LCM could be continued without any apparent side effects. The blood levels of LCM increased linearly to the optimal level. We confirmed excretion of LCM in the PD fluid. Kidney transplantation was done three months after and her seizures were well controlled. CONCLUSIONS: LCM might be a promising option for patients undergoing PD. Due to the lower removal efficacy in PD compared with in HD, close attention should be paid to possible drug excess.

Genome-wide assessment of genetic risk loci for childhood acute lymphoblastic leukemia in Japanese patients.
Mayumi Hangai, Takahisa Kawaguchi, Masatoshi Takagi, Keitaro Matsuo, Soyoung Jeon, Charleston W K Chiang, Andrew T Dewan, Adam J De Smith, Toshihiko Imamura, Yasuhiro Okamoto, Akiko M Saito, Takao Deguchi, Michiaki Kubo, Yoichi Tanaka, Yoko Ayukawa, Toshinari Hori, Kentaro Ohki, Nobutaka Kiyokawa, Takeshi Inukai, Yuki Arakawa, Makiko Mori, Daisuke Hasegawa, Daisuke Tomizawa, Hiroko Fukushima, Yuki Yuza, Yasushi Noguchi, Yuichi Taneyama, Setsuo Ota, Hiroaki Goto, Masakatsu Yanagimachi, Dai Keino, Kazutoshi Koike, Daisuke Toyama, Yozo Nakazawa, Kozue Nakamura, Koichi Moriwaki, Yujin Sekinaka, Daisuke Morita, Shinsuke Hirabayashi, Yosuke Hosoya, Yuri Yoshimoto, Hiroki Yoshihara, Miwa Ozawa, Shinobu Kobayashi, Naho Morisaki, Tshewang Gyeltshen, Osamu Takahashi, Yukinori Okada, Makiko Matsuda, Toshihiro Tanaka, Johji Inazawa, Junko Takita, Yasushi Ishida, Akira Ohara, Catherine Metayer, Joseph L Wiemels, Xiaomei Ma, Shuki Mizutani, Katsuyoshi Koh, Yukihide Momozawa, Keizo Horibe, Fumihiko Matsuda, Motohiro Kato, Atsushi Manabe, Kevin Y Urayama
Haematologica, 2023年10月26日, ［国際誌］
英語, 研究論文（学術雑誌）, Not available.

Prenatal metal concentrations and physical abnormalities in the Japan Environment and Children's Study.
Yuichi Nakamura, Sumitaka Kobayashi, Kazutoshi Cho, Sachiko Itoh, Chihiro Miyashita, Takeshi Yamaguchi, Hiroyoshi Iwata, Naomi Tamura, Yasuaki Saijo, Yoshiya Ito, Yoshitaka Seto, Ryota Honjo, Akiko Ando, Yuta Furuse, Atsushi Manabe, Reiko Kishi
Pediatric research, 2023年10月19日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The association between prenatal metal exposure and congenital anomalies is unclear. We aimed to examine the association between exposure to cadmium, lead, mercury, selenium, and manganese and physical abnormalities. METHODS: Data from 89,887 pregnant women with singleton pregnancies who participated in the Japan Environment and Children's Study (JECS) were used. The correlation between maternal blood metal concentrations and physical abnormalities during the second or third trimester was investigated using logistic regression models. Physical anomalies included those observed at birth or at 1 month, primarily from ICD-10 Chapter 17, particularly congenital anomalies associated with environmental factors (e.g., hypospadias, cryptorchidism, cleft lip and palate, digestive tract atresia, congenital heart disease, and chromosomal abnormalities) and minor abnormalities. RESULTS: After adjusting for covariates, the OR (95% CIs) of physical abnormalities for a one-unit rise in Mn concentrations in all individuals were 1.26 (1.08, 1.48). The OR (95% CIs) of physical abnormalities in the 4th quartile (≥18.7 ng/g) were 1.06 (1.01, 1.13) (p-value for the trend = 0.034) compared with those in the 1st quartile (≤12.5 ng/g). CONCLUSION: In Japan, maternal blood Mn concentrations above threshold during pregnancy may slightly increase the incidence of physical abnormalities. IMPACT: Physical abnormalities (including minor anomalies and congenital anomalies) are associated with prenatal manganese concentrations. They are not associated with cadmium, lead, mercury, and selenium concentrations.

Slow-growing WNT medulloblastoma with atypical magnetic resonance imaging findings: illustrative case.
Makoto Mizushima, Michinari Okamoto, Shigeru Yamaguchi, Sogo Oki, Hiroaki Motegi, Minako Sugiyama, Atsushi Manabe, Ai Shimizu, Kentaro Nishioka, Takayuki Hashimoto, Junko Hirato, Yonehiro Kanemura, Miki Fujimura
Journal of neurosurgery. Case lessons, 6, 7, 2023年08月14日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.

Challenges to Widespread Use of Fertility Preservation Facilities for Pediatric Cancer Patients in Japan.
Tadashi Maezawa, Nao Suzuki, Hiroki Takeuchi, Mikiko Nishioka, Moe Hidaka, Atsushi Manabe, Yuhki Koga, Hiroshi Kawaguchi, Yoji Sasahara, Masahito Tachibana, Shotaro Iwamoto, Akihito Horie, Hidefumi Hiramatsu, Motohiro Kato, Miyuki Harada, Yuki Yuza, Masahiro Hirayama, Junko Takita, Tomoaki Ikeda, Kimikazu Matsumoto
Journal of adolescent and young adult oncology, 2023年08月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Although fertility preservation for pediatric cancer patients is becoming more widespread in Japan, some facilities do not provide sufficient information regarding fertility. This study aimed to elucidate the problems pertaining to the lack of information about fertility among patients. Methods: Based on a 2020 survey, seminars addressing fertility preservation were held from the Designated Pediatric Cancer Care Hospitals in each of the seven blocks in Japan to their partner hospital (pediatric cancer hospitals). The seminar consisted of lectures and group discussions, and a questionnaire was also administered after each seminar. Results: In the group discussions, a lack of explanations to patients and explanatory materials for children were cited as issues by many facilities. The survey results revealed a lack of material explaining fertility preservation and a lack of knowledge among health care providers. There were also many requests to use the patient explanation videos presented at the seminar. Conclusion: The results indicate that further education for health care providers by seminar and other sources and enhancement of explanatory materials are important for fertility preservation in pediatric cancer hospitals in Japan.

Therapeutic Drug Monitoring of Oral Voriconazole in an Infant Less than Six Months of Age and Pharmacokinetics Changes Induced by Development of CYP2C19 in the Growth Process: A Novel Case Report
Atsushi Yamaguchi, Yuki Tazawa, Masashiro Ueki, Masafumi Yamada, Atsushi Manabe, Mitsuru Sugawara, Yoh Takekuma
YAKUGAKU ZASSHI, 143, 6, 545, 549, Pharmaceutical Society of Japan, 2023年06月01日, ［査読有り］
研究論文（学術雑誌）

Efficacy of sirolimus for epileptic seizures in childhood associated with focal cortical dysplasia type II
Hideaki Shiraishi, Tsuyoshi Teramoto, Saki Yokoshiki, Jun Tohyama, Yuki Ueda, Kiyoshi Egawa, Norihiro Sato, Atsushi Manabe, Mitsuhiro Kato
BRAIN & DEVELOPMENT, 45, 6, 343, 347, ELSEVIER, 2023年06月
英語, 研究論文（学術雑誌）, Objective: The efficacy of the mechanistic target of rapamycin inhibitor, sirolimus, was recently reported for patients more than 6 years of age by Kato et al. We evaluated the efficacy and safety of sirolimus in a 2-year-old patient with recurrent focal seizures with impaired consciousness after focal cortical dysplasia (FCD) type IIa resection. Methods: The patient was a 2-year-old girl who had recurrent seizures after undergoing FCD resection at 4 months of age. The initial dose of sirolimus was 0.5 mg/day and was gradually increased using the trough blood concentration before oral administration as an index, and evaluation was performed at 92 weeks. Results: The trough blood level of sirolimus was increased to 6.1 ng/mL and maintenance therapy was started at 40 weeks. Focal seizures with impairment of consciousness with tonic extension of the limbs decreased. No critically serious adverse events occurred. Conclusion: Sirolimus was effective against epileptic seizures from FCD type II even for a child under 5 years of age. There were no critically serious adverse events and administration could be continued. (c) 2023 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

ブスルファンの著しい薬物動態変動が認められた小児の1例
山口 敦史, 武隈 洋, 仁木 加寿子, 平林 真介, 寺下 友佳代, 長谷河 昌孝, 長 祐子, 真部 淳, 菅原 満
TDM研究, 40, 2, 212, 212, (一社)日本TDM学会, 2023年06月
日本語

Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia.
Satoshi Miyamoto, Kevin Y Urayama, Yuki Arakawa, Katsuyoshi Koh, Yuki Yuza, Daisuke Hasegawa, Yuichi Taneyama, Yasushi Noguchi, Masakatsu Yanagimachi, Takeshi Inukai, Setsuo Ota, Hiroyuki Takahashi, Dai Keino, Daisuke Toyama, Junko Takita, Daisuke Tomizawa, Tomohiro Morio, Kazutoshi Koike, Koichi Moriwaki, Yuya Sato, Junya Fujimura, Daisuke Morita, Yujin Sekinaka, Kozue Nakamura, Kazuo Sakashita, Hiroaki Goto, Atsushi Manabe, Masatoshi Takagi
Pediatric hematology and oncology, 1, 7, 2023年05月02日, ［国際誌］
英語, 研究論文（学術雑誌）, Germline genetic variants influence development of pediatric B cell acute lymphoblastic leukemia (B-ALL). Genome-wide association studies (GWAS) have identified several pediatric B-ALL susceptibility loci. IKZF1 and PAX5, transcription factors involved in B cell development, have been reported as susceptibility genes for B-ALL development. Therefore, we hypothesized that rare variants of genes involved in B cell development would be candidate susceptibility loci for pediatric B-ALL. Thus, we sequenced TCF3, a key transcription factor gene involving in B cell development. Saliva DNA from 527 pediatric patients with pediatric B-ALL in remission who were registered with the Tokyo Children's Cancer Study Group (TCCSG) were examined. As a TCF3 gene-based evaluation, the numbers of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were compared with those in cancer-free individuals using data in public databases. As a TCF3 single-variant evaluation, the frequencies of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were also compared with those in control data. TCF3 gene-based analysis revealed significant associations between rare deleterious variants and pediatric B-ALL development. In addition, TCF3 variant-based analysis showed particularly strong association between variant rs372168347 (three in 521 TCCSG and three in the 15780 gnomAD whole genome analysis cohort, p = 0.0006) and pediatric B-ALL development. TCF3 variants are known to influence B cell maturation and may increase the risk of preleukemic clone emergence.

Gタンパク共役型受容体101(GPR101)遺伝子変異を同定した複合型下垂体機能低下症の兄弟例
森川 俊太郎, 金子 直哉, 中山 加奈子, 菱村 希, 山口 健史, 佐々木 大輔, 上田 泰弘, 渡邊 さやか, 青柳 勇人, 中村 明枝, 真部 淳
日本内分泌学会雑誌, 99, 1, 311, 311, (一社)日本内分泌学会, 2023年05月
日本語

北海道の小児医療体制を支える広域搬送システムの有用性
武田 充人, 真部 淳
小児保健研究, 82, 講演集, 133, 133, (公社)日本小児保健協会, 2023年05月
日本語

Changes in bone turnover markers after discontinuing long-term glucocorticoid administration in children with idiopathic nephrotic syndrome: a multicenter retrospective observational study.
Yasuhiro Ueda, Takayuki Okamoto, Yasuyuki Sato, Asako Hayashi, Toshiyuki Takahashi, Ryota Suzuki, Aoyagi H, MICHIHIKO UENO, Kobayashi N, Uetake K, Nakanishi M, Ariga T, Atsushi Manabe
Pediatric nephrology (Berlin, Germany), 2023年04月13日, ［査読有り］
研究論文（学術雑誌）,

Background

Glucocorticoids affect bone turnover. Little is known about how bone turnover changes when glucocorticoids are discontinued following long-term administration.

Methods

This retrospective observational study was conducted on the relationship between discontinuation of long-term administration of glucocorticoid and bone turnover markers (BTMs) in patients with childhood-onset idiopathic nephrotic syndrome. Serum bone alkaline phosphatase (BAP), intact procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were evaluated as BTMs.

Results

Thirty-eight pairs of BTMs at glucocorticoid administration and after discontinuation were analyzed in 29 patients. The median age at baseline was 12.4 (interquartile range, 9.0-14.5) years, and the median time from the onset of nephrotic syndrome was 5.9 (3.3-9.7) years. The mean period from prednisolone discontinuation to the measurement of BTMs after glucocorticoid discontinuation was 3.5 ± 1.0 months. Changes in BTMs after glucocorticoid discontinuation were modest when the daily prednisolone dose was < 0.25 mg/kg/day (ln BAP standard deviation [SD] score, p = 0.19; log intact P1NP SD score, p = 0.70; TRACP-5b, p = 0.95). When the daily prednisolone dose was ≥ 0.25 mg/kg/day, all BTMs increased significantly after glucocorticoid discontinuation (ln BAP SD score, p < 0.01; log intact P1NP SD score, p < 0.01; TRACP-5b, p < 0.01).

Conclusions

Decreased BTMs can rise within a few months of discontinuing long-term glucocorticoid administration. When the administered glucocorticoid dose is low, changes in BTMs may be small. A higher resolution version of the Graphical abstract is available as Supplementary information.

Outcomes following induction failure in Japanese children with acute lymphoblastic leukemia.
Chihaya Imai, Atsushi Sato, Mitsuteru Hiwatari, Yasuto Shimomura, Toshinori Hori, Souichi Suenobu, Toshihiko Imamura, Junichi Hara, Daisuke Hasegawa, Hiroyuki Takahashi, Kunihiko Moriya, Saori Katayama, Daisuke Tomizawa, Hiroshi Moritake, Takashi Taga, Keizo Horibe, Katsuyoshi Koh, Atsushi Manabe, Yasuhiro Okamoto
International journal of hematology, 118, 1, 99, 106, 2023年04月10日, ［国内誌］
英語, 研究論文（学術雑誌）, The characteristics and prognosis of Japanese children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission after remission induction chemotherapy (i.e., experience induction failure) are poorly understood. Therefore, we retrospectively analyzed data of patients enrolled in Japanese clinical trials for newly diagnosed ALL between 1996 and 2009. Among 4956 participants, 89 (1.8%) experienced induction failure. With a 6.0-year median follow-up, the 5-year overall survival rate of the entire cohort was 43.0% ± 5.5%. Survival rates did not differ between patients with B-cell precursor ALL (BCP-ALL) and T-cell ALL (T-ALL). In multivariate analysis, day 15 M3 marrow (bone marrow blast count ≥ 25%) was significantly correlated with poorer survival in the whole or BCP-ALL cohorts. In T-ALL, age < 6 years was significantly associated with poor survival. However, due to the small sample size, this correlation must be further investigated. Most T-ALL and BCR-ABL-positive BCP-ALL patients underwent allogeneic stem cell transplantation (allo-SCT). Survival rates did not differ between BCR-ABL-negative BCP-ALL patients who did and did not undergo allo-SCT, possibly due to the inclusion of lower-risk patients in the latter group. In conclusion, the induction failure rate and survival after diagnosis of induction failure in our study were comparable to previously reported figures.

前思春期のビスフェノール類曝露と性・ステロイドホルモン値との関連 北海道スタディ
池田 敦子, 山口 健史, アイツバマイ ゆふ, 池中 良徳, ケテマ・ラヘルメスフィ, 曾 怡, 中村 明枝, 橘田 岳也, 今 雅史, 篠原 信雄, 真部 淳, 宮下 ちひろ, コバチ・アドリアン, 岸 玲子
日本衛生学雑誌, 78, Suppl., S181, S181, (一社)日本衛生学会, 2023年03月
日本語

高用量ステロイド吸入により医原性グルココルチコイド過剰および二次性副腎皮質機能不全をきたした女児例
小野 夏実, 金子 直哉, 中山 加奈子, 菱村 希, 山口 健史, 森川 俊太郎, 真部 淳, 中村 明枝
臨床小児医学, 70, 1-6, 57, 63, (財)小児愛育協会, 2023年03月
日本語, 副腎皮質ステロイドは多くの疾患の治療に欠かせない薬剤である一方,その副作用は多岐にわたる。今回われわれは,気管支喘息治療に用いた吸入ステロイドが原因で,グルココルチコイド過剰症状と二次性副腎皮質機能不全を呈した11歳女児例を経験した。吸入ステロイドを開始した3年後に成長率低下,易疲労感を主訴に近医受診し,随時採血で血漿ACTH,血清コルチゾールは測定感度未満であった。当院で入院精査を行い,吸入ステロイドが原因となった二次性副腎皮質機能低下症と診断した。吸入ステロイドの漸減中止とともに成長率は改善し,副腎皮質機能も回復した。全身性のステロイド投与による二次性副腎皮質機能低下症は比較的よく知られる病態であるが,本症例のように吸入ステロイドを高用量で長期間に渡って使用する場合でも,副腎機能に留意する必要がある。(著者抄録)

Sunburst appearanceを呈する頭蓋骨腫瘤を契機に発見された神経芽腫の1例　　　　　　　　　　　　　　　
北川 悠, 竹中 淳規, 渡邊 史郎, 平田 健司, 内山 裕子, 木村 理奈, 中川 純一, 池辺 洋平, 長谷河 昌孝, 澤井 彩織, 寺下 友佳代, 杉山 未奈子, 平林 真介, 長 祐子, 山口 秀, 真部 淳, 工藤 與亮
北海道放射線医学雑誌, 3, 33, 36, (NPO)メディカルイメージラボ, 2023年03月
日本語, 症例は9歳女児。左頭部腫瘤を主訴に近医を受診し、頭部CTで左前頭骨にsunburst appearanceを呈する腫瘤性病変を指摘され、その他にも右頭頂骨と左下顎頭に骨病変を認めた。体幹部造影CTを施行したところ、後縦隔の胸椎椎体前方から左側にかけて巨大な軟部腫瘤を認めた。血清神経特異エノラーゼ(NSE)や尿中バニリルマンデル酸(VMA)/ホモバニリン酸(HVA)が高値であり、神経芽腫が第一に疑われた。123I-MIBGシンチグラフィを施行したところ、後縦隔腫瘤のほか頭蓋骨を含めた全身骨にも集積が見られ、神経芽腫とその骨転移が疑われた。頭蓋骨腫瘤の生検術により神経芽腫の診断が確定した。神経芽腫は小児期に発生する頭蓋外の固形悪性腫瘍の中で最も頻度が高い。転移性頭蓋骨腫瘍がsunburst appearanceを呈することは比較的稀であるが、小児では神経芽腫の転移でしばしば経験される。神経芽腫の骨転移の部位として、頭蓋骨は頻度が高く、小児においてsunburst appearanceを呈し多発する頭蓋骨腫瘤を見た場合には神経芽腫の骨転移を考慮する必要がある。(著者抄録)

小児がん経験者(CCS)フォロー中に甲状腺がんを発症した4例
金子 直哉, 菱村 希, 寺下 友佳代, 中山 加奈子, 山口 健史, 森川 俊太郎, 長谷河 昌孝, 澤井 彩織, 杉山 未奈子, 平林 真介, 長 祐子, 真部 淳, 中村 明枝
日本内分泌学会雑誌, 98, 4, 719, 719, (一社)日本内分泌学会, 2023年02月
日本語

A nationwide survey of late effects in survivors of juvenile myelomonocytic leukemia in Japan.
Shuichi Ozono, Kazuo Sakashita, Nao Yoshida, Harumi Kakuda, Kenichiro Watanabe, Miho Maeda, Yasushi Ishida, Atsushi Manabe, Takashi Taga, Hideki Muramatsu
Pediatric blood & cancer, 70, 2, e30126, 2023年02月, ［国際誌］
英語, 研究論文（学術雑誌）, We conducted a cross-sectional study using a questionnaire to explore the late effects in survivors of allogenic hematopoietic stem cell transplantation (HSCT) for juvenile myelomonocytic leukemia (JMML). The attending pediatric hematologists/oncologists completed the questionnaires. Of the 30 survivors, approximately 83% showed more than one late effect. The identified late effects included endocrine, dental, skin, ophthalmologic, musculoskeletal, pulmonary, neurocognitive, and cardiovascular dysfunction. The prevalence of short stature, pulmonary, cardiovascular, and nephrological complications was significantly elevated among survivors who were 12 years or more lapsed after HSCT. Therefore, a multidisciplinary follow-up system for survivors of JMML is crucial.

Therapeutic effects of KRM-II-81, positive allosteric modulator for α2/3 subunit containing GABAA receptors, in a mouse model of Dravet syndrome.
Sachiko Nakakubo, Yasuyoshi Hiramatsu, Takeru Goto, Syuhei Kimura, Masashi Narugami, Midori Nakajima, Yuki Ueda, Hideaki Shiraishi, Atsushi Manabe, Dishary Sharmin, James M Cook, Kiyoshi Egawa
Frontiers in pharmacology, 14, 1273633, 1273633, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development. Here, we evaluated the effects of KRM-II-81, a newly developed positive allosteric modulator for α 2/3 subunit containing GABAA receptors (α2/3-GABAAR) in a mice model of DS both in vivo and at the neuronal level. Methods: We used knock-in mice carrying a heterozygous, clinically relevant SCN1A mutation (background strain: C57BL/6 J) as a model of the DS (Scn1a WT/A1783V mice), knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V). Seizure threshold and locomotor activity was evaluated by using the hyperthermia-induced seizure paradigm and open filed test, respectively. Anxiety-like behavior was assessed by avoidance of the center region in locomotor activity. We estimated a sedative effect by the total distance traveled in locomotor activity and grip strength. Inhibitory post synaptic currents (IPSCs) were recorded from a hippocampal CA1 pyramidal neuron in an acutely prepared brain slice. Results: KRM-II-81 significantly increased the seizure threshold of Scn1a WT/A1783V mice in a dose-dependent manner. A low dose of KRM-II-81 specifically improved anxiety-like behavior of Scn1a WT/A1783V mice. A sedative effect was induced by relatively high dose of KRM-II-81 in Scn1a WT/A1783V mice, the dose of which was not sedative for WT mice. KRM-II-81 potentiated IPSCs by increasing its decay time kinetics. This effect was more prominent in Scn1a WT/A1783V mice. Discussion: Higher activation of α2/3-GABAAR by KRM-II-81 suggests a compensatory modification of post synaptic inhibitory function against presynaptic inhibitory dysfunction in Scn1a WT/A1783V. The increased sensitivity for KRM-II-81 may be relevant to the distinct dose-dependent effect in each paradigm of Scn1a WT/A1783V mice. Conclusion: Selective activation for α2/3-GABAAR by KRM-II-81 could be potential therapeutic strategy for treating seizures and behavioral problems in DS.

The heterozygous NUDT15 variant is not associated with the severity of 6-mercaptopurine-related side effects in early intensification therapy for childhood acute lymphoblastic leukemia
Jimei Zhao, Masahiro Ueki, Saori Sawai, Minako Sugiyama, Yukayo Terashita, Shinsuke Hirabayashi, Yuko Cho, Ryoji Kobayashi, Yoichi Tanaka, Atsushi Manabe
EJC Paediatric Oncology, 1, 100006, 100006, Elsevier BV, 2023年
研究論文（学術雑誌）

Preterm toddlers have low nighttime sleep quality and high daytime activity.
Yoko Asaka, Yusuke Mitani, Hidenobu Ohta, Takayo Nakazawa, Rika Fukutomi, Kyoko Kobayashi, Mayuko Kumagai, Hitomi Shinohara, Michiko Yoshida, Akiko Ando, Yuko Yoshimura, Machiko Nakagawa, Yoshihisa Oishi, Masato Mizushima, Hiroyuki Adachi, Yosuke Kaneshi, Keita Morioka, Yoshitaka Seto, Rinshu Shimabukuro, Michio Hirata, Takashi Ikeda, Miwa Ozawa, Masahiro Takeshima, Atsushi Manabe, Tsutomu Takahashi, Kazuo Mishima, Mitsuru Kikuchi, Hitoshi Yoda, Isao Kusakawa, Kazutoshi Cho
Scientific reports, 12, 1, 20032, 20032, 2022年11月21日, ［国際誌］
英語, 研究論文（学術雑誌）, A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers' waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.

Clinical characteristics and outcomes of B-cell precursor ALL with MEF2D rearrangements: a retrospective study by the Ponte di Legno Childhood ALL Working Group.
Kentaro Ohki, Ellie R Butler, Nobutaka Kiyokawa, Shinsuke Hirabayashi, Anke K Bergmann, Anja Möricke, Judith M Boer, Hélène Cavé, Giovanni Cazzaniga, Allen Eng Juh Yeoh, Masashi Sanada, Toshihiko Imamura, Hiroto Inaba, Charles G Mullighan, Mignon L Loh, Ulrika Norén-Nyström, Lee-Yung Shih, Marketa Zaliova, Ching-Hon Pui, Oskar A Haas, Christine J Harrison, Anthony V Moorman, Atsushi Manabe
Leukemia, 2022年10月29日, ［国際誌］
英語, 研究論文（学術雑誌）

Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.
Shigeru Yamaguchi, Michinari Okamoto, Yukitomo Ishi, Ryosuke Sawaya, Hiroaki Motegi, Minako Sugiyama, Taisuke Harada, Noriyuki Fujima, Takashi Mori, Takayuki Hashimoto, Emi Takakuwa, Atsushi Manabe, Kohsuke Kudo, Hidefumi Aoyama, Miki Fujimura
Journal of neurosurgery. Pediatrics, 1, 8, 2022年09月09日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. METHODS: The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. RESULTS: Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. CONCLUSIONS: End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

Prominence of NUDT15 genetic variation associated with 6‐mercaptopurine tolerance in a genome‐wide association study of Japanese children with acute lymphoblastic leukaemia
Yoichi Tanaka, Kevin Y. Urayama, Makiko Mori, Yuki Arakawa, Daisuke Hasegawa, Yasushi Noguchi, Masakatsu Yanagimachi, Dai Keino, Setsuo Ota, Koshi Akahane, Takeshi Inukai, Mayumi Hangai, Takahisa Kawaguchi, Masatoshi Takagi, Katsuyoshi Koh, Fumihiko Matsuda, Atsushi Manabe
British Journal of Haematology, 199, 2, 260, 269, Wiley, 2022年08月12日
研究論文（学術雑誌）

腹膜透析中に発症した焦点性てんかんに対してラコサミドを導入した小児例の経験　　　　　　　　　　　　　　　
植田 佑樹, 佐藤 泰征, 林 麻子, 上田 泰弘, 木村 修平, 後藤 健, 中久保 佐千子, 中島 翠, 江川 潔, 岡本 孝之, 白石 秀明, 古堅 彩子, 小林 正紀, 真部 淳
てんかん研究, 40, 2, 467, 467, (一社)日本てんかん学会, 2022年08月
日本語

北海道における成人先天性心疾患の移行医療からみえてくるもの
武田 充人, 山澤 弘州, 泉 岳, 佐々木 大輔, 永井 礼子, 辻岡 孝郎, 真部 淳
小児保健研究, 81, 講演集, 134, 134, (公社)日本小児保健協会, 2022年05月
日本語

A retrospective analysis of azacitidine treatment for juvenile myelomonocytic leukemia.
Yuko Honda, Hideki Muramatsu, Yuka Nanjo, Shinsuke Hirabayashi, Toru Meguro, Nao Yoshida, Harumi Kakuda, Shuichi Ozono, Manabu Wakamatsu, Hiroshi Moritake, Masahiro Yasui, Hideki Sano, Atsushi Manabe, Kazuo Sakashita
International journal of hematology, 115, 2, 263, 268, 2022年02月, ［国内誌］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia (JMML) is a pediatric hematological malignancy with a poor prognosis. Although several case series have been published describing hematological and molecular responses to azacitidine (AZA) treatment in patients with JMML, the efficacy and safety profile of AZA is not well investigated, especially in Asian children and children undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 5 patients who received a total of 12 cycles (median 2 cycles) of AZA treatment in Japan. All five patients were boys and their ages at the time of treatment were 21, 23, 24, 26, and 46 months, respectively. All five patients tolerated AZA treatment, including four patients who received AZA after HSCT. Therapeutic toxicity with AZA was mostly limited to hematological toxicity. The only serious non-hematological adverse event was hyperbilirubinemia (grades III-IV) observed in a patient who received AZA after a second HSCT. Two out of five patients treated with AZA achieved a partial response (PR), while three patients treated for post-transplant relapse did not have an objective response. Future prospective studies should be conducted to develop combination therapies with AZA and other molecular targeted drugs for high-risk patients.

Prospective validation of the provisional entity of refractory cytopenia of childhood, proposed by the World Health Organization.
Asahito Hama, Daisuke Hasegawa, Atsushi Manabe, Kazue Nozawa, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Kosaka, Masao Kobayashi, Katsuyoshi Koh, Yoshiyuki Takahashi, Kenichiro Watanabe, Akira Ohara, Masafumi Ito, Seiji Kojima
British journal of haematology, 196, 4, 1031, 1039, 2022年02月, ［国際誌］
英語, 研究論文（学術雑誌）, In 2008, the World Health Organization proposed a new entity of childhood myelodysplastic syndrome (MDS), which was referred to as refractory cytopenia of childhood (RCC). However, whether this morphological classification reflects clinical outcomes remains unclear. We performed a prospective evaluation of bone marrow morphology in 252 children with acquired bone marrow failure between 2009 and 2013. Of 252 patients, 63 were diagnosed with aplastic anaemia (AA), 131 with RCC without multilineage dysplasia (RCC-w/o-MLD) and 58 with RCC with MLD (RCC-MLD). One patient with AA, three with RCC-w/o-MLD and nine with RCC-MLD presented with chromosomal abnormalities at diagnosis (P = 0·001). The response rates to immunosuppressive therapy (IST) at 6 months and the cumulative incidence of clonal evolution at 5 years did not significantly differ among the three groups. A multivariate analysis revealed that the morphological classification of RCC-MLD was a significant risk factor for secondary graft failure after haematopoietic cell transplantation (HCT) (P = 0·003). In view of these findings, RCC could be divided into two categories, RCC-w/o-MLD and RCC-MLD, because children with this condition exhibited a distinct morphology, frequent chromosomal abnormalities at diagnosis and a high frequency of secondary graft failure after HCT.

Factors related to employment in childhood cancer survivors in Japan: A preliminary study.
Kyoko Kobayashi, Yasushi Ishida, Michiyo Gunji, Kyoko Nagase, Yuri Yoshimoto-Suzuki, Yosuke Hosoya, Daisuke Hasegawa, Atsushi Manabe, Sachiko Ohde, Miwa Ozawa
Frontiers in pediatrics, 10, 961935, 961935, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Previous research has revealed vocational and academic difficulties in childhood cancer survivors, and explored impact of survivors' medical history and physical function on vocational and academic status. However, we often encounter survivors with similar diagnoses and late effects but different academic or employment statuses. This raises the question of what affects academic attainment and employment other than treatment or late effects. This study aimed to explore factors associated with childhood cancer survivors' employment status and academic achievement. METHODS: Comprehensive health check-up and questionnaire survey were conducted for 69 survivors who were over the age of 18 and participated in St. Luke's Lifetime cohort study. We obtained survivors' biological function using comprehensive health check-up, neurocognitive states, quality of life, transition readiness, and family function. We conducted univariate analysis (Mann-Whitney U tests or chi-square tests) to compare the differences between the regular workers/students and non-regular workers/unemployed groups. The variables with p-values <0.1 were used as independent variables multivariate logistic regression to explore predictors of employment status and academic attainment. RESULTS: Result of the univariate analysis, intelligence quotient, SF-8 PCS, transition readiness, family function were used for multivariate logistic regression as independent variables. The stepwise likelihood method was conducted; intelligence quotient (odds ratio [OR] = 1.100; 95% confidence interval [CI] 1.015-1.193; p = 0.021), transition readiness (OR = 0.612; 95% CI 0.396-0.974; p = 0.038), and family function (OR = 2.337; 95% CI 1.175-4.645; p = 0.015) were found to be associated with survivors' regular workers/students in the final regression model. CONCLUSION: Long-term follow-up of pediatric cancer survivors requires the provision of total care, which supports physical, psychological, and social functions to improve health, readiness for transition to self-management, and family functioning.

Significance of active screening for detection of health problems in childhood cancer survivors.
Yuri Yoshimoto-Suzuki, Daisuke Hasegawa, Yosuke Hosoya, Go Saito, Kyoko Nagase, Michiyo Gunji, Kyoko Kobayashi, Yasushi Ishida, Atsushi Manabe, Miwa Ozawa
Frontiers in pediatrics, 10, 947646, 947646, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Childhood cancer survivors (CCSs) have a lifelong increased risk of chronic health problems, most of which are associated with the curative therapies. Recent studies have suggested that prospective active screening using comprehensive assessments for CCSs is superior in identifying undiagnosed chronic health problems. Methods: To assess the significance of active screening using comprehensive medical examinations for detecting chronic health problems in multiple organ systems in CCSs, we retrospectively compared the frequency and severity of health problems between two different cohorts of CCSs in a single institution: 110 CCSs who visited the outpatient clinic for regular follow-ups between December 2010 and December 2015 (regular follow-up group) vs. 58 CCSs who underwent comprehensive medical examinations between February 2016 and September 2019 (active screening group). CCSs were defined as patients aged ≥ 18 years who had been diagnosed as having childhood cancer ≥ 10 years before and had survived without cancer for ≥ 5 years. Results: Patient characteristics were similar between the two groups except for primary diagnosis (more brain tumors and embryonal tumors in the active screening group) and treatment history (more alkylating agents used and surgical interventions performed in the active screening group). The prevalence and the median number of health problems were significantly higher in the active screening group than in the regular follow-up group: 93% vs. 67% and 1.0 [0.0-8.0] vs. 2.0 [0.0-7.0] respectively. In term of organ-specific health problems, pulmonary dysfunction, neurocognitive impairment, ocular abnormalities, and dental abnormalities were identified more in the active screening group, partly because these problems had not been assessed in the regular follow-up group. Nevertheless, the prevalence of grade 3-5 health problems was similar between the two groups, except for pulmonary dysfunction. Conclusion: Active screening using comprehensive medical examinations was effective for identifying health problems in CCSs. Although the prevalence of severe problems identified by both approaches was similar, comprehensive medical examinations could detect overlooked problems such as severe pulmonary dysfunction, dental maldevelopment, and borderline intellectual functioning, which might have an impact on quality of life in CCSs.

Intrathecal therapy in acute lymphoblastic leukemia case with spinal deformity.
Yurika Kuroko, Hiroki Yoshihara, Yosuke Hosoya, Atsushi Manabe, Daisuke Hasegawa
Pediatrics international : official journal of the Japan Pediatric Society, 64, 1, e14845, 2022年01月, ［国際誌］
英語, 研究論文（学術雑誌）

Hepatoblastoma with bone/bone marrow metastasis in Li-Fraumeni syndrome patient.
Masataka Hasegawa, Minako Sugiyama, Yukayo Terashita, Yuko Cho, Atsushi Manabe
Pediatrics international : official journal of the Japan Pediatric Society, 64, 1, e15135, 2022年01月, ［国際誌］
英語, 研究論文（学術雑誌）

NUDT15 variants confer high incidence of second malignancies in children with acute lymphoblastic leukemia.
Masanori Yoshida, Kazuhiko Nakabayashi, Wentao Yang, Aiko Sato-Otsubo, Shin-Ichi Tsujimoto, Hiroko Ogata-Kawata, Tomoko Kawai, Keisuke Ishiwata, Mika Sakamoto, Kohji Okamura, Kaoru Yoshida, Ryota Shirai, Tomoo Osumi, Takaya Moriyama, Rina Nishii, Hiroyuki Takahashi, Chikako Kiyotani, Yoko Shioda, Keita Terashima, Sae Ishimaru, Yuki Yuza, Masatoshi Takagi, Yuki Arakawa, Akitoshi Kinoshita, Moeko Hino, Toshihiko Imamura, Daisuke Hasegawa, Yozo Nakazawa, Mayuko Okuya, Harumi Kakuda, Nao Takasugi, Akiko Inoue, Kentaro Ohki, Takako Yoshioka, Shuichi Ito, Daisuke Tomizawa, Katsuyoshi Koh, Kimikazu Matsumoto, Masashi Sanada, Nobutaka Kiyokawa, Akira Ohara, Seishi Ogawa, Atsushi Manabe, Akira Niwa, Kenichiro Hata, Jun J Yang, Motohiro Kato
Blood advances, 5, 23, 5420, 5428, 2021年12月14日, ［国際誌］
英語, 研究論文（学術雑誌）, The effect of genetic variation on second malignant neoplasms (SMNs) remains unclear. First, we identified the pathogenic germline variants in cancer-predisposing genes among 15 children with SMNs after childhood leukemia/lymphoma using whole-exome sequencing. Because the prevalence was low, we focused on the association between SMNs and NUDT15 in primary acute lymphoblastic leukemia (ALL) cases. NUDT15 is one of the 6-mercaptopurine (6-MP) metabolic genes, and its variants are common in East Asian individuals. The prevalence of NUDT15 hypomorphic variants was higher in patients with SMNs (n = 14; 42.9%) than in the general population in the gnomAD database (19.7%; P = .042). In the validation study with a cohort of 438 unselected patients with ALL, the cumulative incidence of SMNs was significantly higher among those with (3.0%; 95% confidence interval [CI], 0.6% to 9.4%) than among those without NUDT15 variants (0.3%; 95% CI, 0.0% to 1.5%; P = .045). The 6-MP dose administered to patients with ALL with a NUDT15 variant was higher than that given to those without SMNs (P = .045). The 6-MP-related mutational signature was observed in SMN specimens after 6-MP exposure. In cells exposed to 6-MP, a higher level of 6-MP induced DNA damage in NUDT15-knockdown induced pluripotent stem cells. Our study indicates that NUDT15 variants may confer a risk of SMNs after treatment with 6-MP in patients with ALL.

Notable therapeutic response in a patient with systemic juvenile xanthogranuloma with KIF5B-ALK fusion.
Minako Sugiyama, Shinsuke Hirabayashi, Yukitomo Ishi, Junko Kikuchi, Ayako Ishikura, Hiroaki Motegi, Yuki Ueda, Saori Sawai, Kazuya Hara, Yukayo Terashita, Yuko Cho, Emi Takakuwa, Shohei Honda, Shigeru Yamaguchi, Ichiro Kinoshita, Atsushi Manabe
Pediatric blood & cancer, 68, 11, e29227, 2021年11月, ［国際誌］
英語

Hematopoietic stem cell transplantation for infants with high-risk KMT2A gene-rearranged acute lymphoblastic leukemia.
Takayuki Takachi, Tomoyuki Watanabe, Takako Miyamura, Akiko Moriya Saito, Takao Deguchi, Toshinori Hori, Tomomi Yamada, Shigeru Ohmori, Masami Haba, Yuki Aoki, Sae Ishimaru, Shinya Sasaki, Junjiro Ohshima, Akihiro Iguchi, Yoshiyuki Takahashi, Nobuyuki Hyakuna, Atsushi Manabe, Keizo Horibe, Eiichi Ishii, Katsuyoshi Koh, Daisuke Tomizawa
Blood advances, 5, 19, 3891, 3899, 2021年10月12日, ［国際誌］
英語, 研究論文（学術雑誌）, The role of allogeneic hematopoietic stem cell transplantation (HSCT) for infants with acute lymphoblastic leukemia (ALL) and KMT2A gene rearrangement (KMT2A-r) is controversial in terms of both its efficacy and potential for acute and late toxicities. In Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10, by introducing intensive chemotherapy, indication of HSCT was restricted to patients with high-risk (HR) features only (KMT2A-r and either age <180 days or presence of central nervous system leukemia). Of the 56 HR patients, 49 achieved complete remission. Forty-three patients received HSCT in first remission including 38 patients receiving protocol-specified HSCT with conditioning consisting of individualized targeted doses of busulfan, etoposide, and cyclophosphamide. Three-year event-free survival (EFS) of 56.8% (95% confidence interval [CI], 42.4% to 68.8%) and overall survival of 80.2% (95% CI, 67.1% to 88.5%) were accomplished. Univariable analysis showed that Interfant-HR criteria and flow cytometric minimal residual disease (MRD; ≥0.01%), both at the end of induction and at the end of consolidation (EOC), were significantly associated with poorer EFS. In the multivariable analysis, positive MRD at EOC was solely associated with poor EFS (P < .001). Rapid pretransplant MRD clearance and tailored HSCT strategy in the MLL-10 trial resulted in a favorable outcome for infants with HR KMT2A-r ALL. However, considering the high rate of potentially life-threatening toxicities and the risk of late effects, its indication should be further restricted or even eliminated in the future by introducing more effective therapeutic modalities with minimal toxicities. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

芽球性形質細胞様樹状細胞腫瘍の小児に対する造血細胞移植を回避した治療(Treatment in pediatric blastic plasmacytoid dendritic cell neoplasm(BPDCN) without transplantation)　　　　　　　　　　　　　　　
足洗 美穂, 西村 聡, 水城 和義, 出口 隆生, 真部 淳, 長谷川 大輔
日本血液学会学術集会, 83回, PS, 5, (一社)日本血液学会, 2021年09月
英語

Prospective validation of the provisional entity of RCC proposed by the WHO(和訳中)　　　　　　　　　　　　　　　
濱 麻人, 真部 淳, 長谷川 大輔, 野沢 和江, 成田 敦, 村松 秀城, 高橋 義行, 渡邉 健一郎, 小原 明, 伊藤 雅文, 小島 勢二
日本血液学会学術集会, 83回, OS1, 2, (一社)日本血液学会, 2021年09月
英語

Treatment in pediatric blastic plasmacytoid dendritic cell neoplasm(BPDCN) without transplantation(和訳中)　　　　　　　　　　　　　　　
足洗 美穂, 西村 聡, 水城 和義, 出口 隆生, 真部 淳, 長谷川 大輔
日本血液学会学術集会, 83回, PS, 5, (一社)日本血液学会, 2021年09月
英語

Risk factors for hospitalisation due to respiratory syncytial virus infection in children receiving prophylactic palivizumab.
Ayako Chida-Nagai, Hiroki Sato, Itsumi Sato, Masahiro Shiraishi, Daisuke Sasaki, Gaku Izumi, Hirokuni Yamazawa, Kazutoshi Cho, Atsushi Manabe, Atsuhito Takeda
European journal of pediatrics, 181, 2, 539, 547, 2021年08月21日, ［国際誌］
英語, 研究論文（学術雑誌）, Respiratory syncytial virus (RSV) is a common pathogen that causes extremely severe respiratory symptoms in the first few weeks and months of life. In infants with cardiopulmonary diseases, RSV infections have a significant clinical impact. Palivizumab, a humanised monoclonal antibody for RSV, has been shown to significantly reduce the rate of hospitalisation of high-risk infants diagnosed with RSV. However, we have experienced a significant number of RSV infections in our institution that required hospitalisation or intensive care, despite the administration of palivizumab. This study aimed to analyse the risk factors associated with severe RSV despite the use of palivizumab. We retrospectively reviewed the medical records of 688 patients who visited or were admitted to our hospital and received palivizumab. Thirty-seven (5.4%) patients required hospitalisation for RSV, despite receiving palivizumab. In addition, 31 of these patients (83.8%) required hospitalisation out of season for palivizumab injection. Preterm birth (≤ 28-week gestation), bronchopulmonary dysplasia (BPD), and trisomy 21 were risk factors for RSV-related hospitalisation in infected patients, despite receiving palivizumab. Furthermore, subgroup analysis of 69 patients with RSV revealed that hemodynamically significant congenital heart disease (CHD) was also a risk factor for RSV-related hospitalisation.Conclusion: Preterm birth (≤ 28 weeks of gestation), BPD, trisomy 21, hemodynamically significant CHD, and CHD requiring surgery or cardiac catheterisation/intervention during infancy could be considered when determining whether year-round administration of palivizumab is appropriate. What is Known: • Respiratory syncytial virus causes severe respiratory symptoms in infants, particularly those with cardiopulmonary diseases. • The use of palivizumab has reduced the rate of hospitalisation of infants diagnosed with RSV. Despite this, the rate of hospitalisation is still high. What is New: • We identified that preterm birth (≤ 28-week gestation), bronchopulmonary dysplasia, trisomy 21, and hemodynamically significant congenital heart disease were risk factors for RSV-related hospitalisation, even after receiving palivizumab treatment. • High-risk infants should be closely monitored and the prolonged use of palivizumab should be considered.

Clonal evidence for the development of neuroblastoma with extensive copy-neutral loss of heterozygosity arising in a mature teratoma.
Rintaro Ono, Hiroo Ueno, Kenichi Yoshida, Satoko Takahashi, Hiroki Yoshihara, Taiki Nozaki, Koyu Suzuki, Atsuko Nakazawa, Ryunosuke Saiki, Masafumi Seki, Junko Takita, Seishi Ogawa, Atsushi Manabe, Daisuke Hasegawa
Cancer science, 112, 7, 2921, 2927, 2021年07月, ［国際誌］
英語, Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral loss of heterozygosity (LOH) in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma. In addition, several truncating germline heterozygous variants in tumor suppressor genes, including RBL2 and FBXW12, became homozygous as a result of LOH. Collectively, we speculate that extensive LOH in teratoma cells may force heterozygous germline variants to become homozygous, which, in turn, may contribute to the development of neuroblastoma with the acquisition of additional chromosomal changes.

Extremely low 18F-fluorodeoxyglucose uptake in the brain of a patient with metastatic neuroblastoma and its recovery after chemotherapy: A case report.
Yutaka Hoshino, Minako Sugiyama, Kenji Hirata, Shohei Honda, Hitoshi Saito, Atsushi Manabe, Kohsuke Kudo
Acta radiologica open, 10, 7, 20584601211026810, 20584601211026810, 2021年07月, ［国際誌］
英語, Commonly, physiological 18F-fluorodeoxyglucose (FDG) uptake in the brain can be observed in 18F-FDG positron emission tomography. Abnormal uptake of 18F-FDG in the brain suggests disorders of central nervous system. Here, we present a case of extremely low 18F-FDG uptake in the brain of a 4-year-old girl with whole-body metastatic neuroblastoma. Almost missing of physiological 18F-FDG uptake in the brain was ascribed at least partly to the metastatic neuroblastoma. The brain could regain physiological 18F-FDG uptake after chemotherapy.

Absent XIAP expression in T cell blasts and causal XIAP mutations including non-coding deletion.
Shimaa Said Mohamed Ali Abdrabou, Nariaki Toita, Shin Ichihara, Yusuke Tozawa, Michiko Takahashi, Shin-Ichi Fujiwara, Toshifumi Ashida, Osamu Ohara, Tadashi Ariga, Atsushi Manabe, Mutsuko Konno, Masafumi Yamada
Pediatrics international : official journal of the Japan Pediatric Society, 64, 1, e14892, 2021年06月18日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is one of inborn errors of immunity characterized by recurrent hemophagocytic lymphohistiocytosis (HLH) and refractory inflammatory bowel disease (IBD) mimicking Crohn's disease (CD). The aim of this study is to make accurate diagnosis of XIAP deficiency based on genetic and XIAP expression studies and to investigate endoscopic findings shared by patients with this disease. METHODS: Four male patients with recurrent HLH and long-term refractory IBD were studied for the diagnosis of XIAP deficiency. Parallelly, endoscopic findings of the four patients were also studied. RESULTS: These four patients were diagnosed with XIAP deficiency based on the absent XIAP expression in cultured T-cell blasts. Sequence analysis of the responsible gene, XIAP, demonstrated two novel nonsense mutations of p.Gln114X and p.Glu25X, and a previously reported nonsense mutation of p.Arg381X. Although no mutations in the coding region were detected in the fourth patient, further studies demonstrated a novel 2199 bp deletion encompassing non-coding exon 1, presumably affecting transcription and stability of XIAP mRNA. All of the patients eventually underwent hematopoietic stem cell transplantation, leading to a complete or partial remission of IBD. These four patients shared an endoscopic finding of multiple wide and longitudinal ulcers with straight and non-raised edge in the colon. CONCLUSIONS: XIAP expression in T-cell blasts could facilitate the diagnosis of this disease especially with causal mutations in non-coding regions.

Clinical significance of comprehensive genomic profiling tests covered by public insurance in patients with advanced solid cancers in Hokkaido, Japan
Junko Kikuchi, Yoshihito Ohhara, Kohichi Takada, Hiroki Tanabe, Kazuteru Hatanaka, Toraji Amano, Kanako C Hatanaka, Yutaka Hatanaka, Takashi Mitamura, Momoko Kato, Yuka Shibata, Ichiro Yabe, Akira Endoh, Yoshito Komatsu, Yoshihiro Matsuno, Minako Sugiyama, Atsushi Manabe, Akihiro Sakurai, Masato Takahashi, Hirohito Naruse, Yoshihiro Torimoto, Hirotoshi Dosaka-Akita, Ichiro Kinoshita
Japanese Journal of Clinical Oncology, 51, 5, 753, 761, Oxford University Press (OUP), 2021年04月30日
研究論文（学術雑誌）,


Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019.





We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020.





All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling.





The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.

Flurothyl-induced seizure paradigm revealed higher seizure susceptibility in middle-aged Angelman syndrome mouse model.
Kiyoshi Egawa, Sachiko Nakakubo, Shuhei Kimura, Takeru Goto, Atsushi Manabe, Hideaki Shiraishi
Brain & development, 43, 4, 515, 520, 2021年04月, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Epilepsy is one of the main clinical problems in Angelman syndrome (AS). Seizures typically start in early childhood then decrease or are often alleviated by young adulthood. Several studies using AS model mice showed comparable seizure susceptibility during young adulthood. In contrast, the course of epilepsy post young adulthood differs from persistently relieved to rerising among reports. To elucidate this, we evaluated the seizure susceptibility of AS model mice of two different ages. METHODS: Mice lacking maternal Ube3a gene (Ube3am-/p+) of C57BL/6 background or their littermate wild type (WT) were divided into two groups by age, 2 to 3 months (2-3 M) and 6 to 12 months (6-12 M), corresponding to adolescent to young adult aged and middle aged humans, respectively. Seizure susceptibility was evaluated by flurothyl inhalation or intraperitoneal injection of pentylenetetrazole (PTZ IP)-induced acute seizure protocol. RESULTS: In the flurothyl-induced seizure paradigm, the latency to seizure occurrence had a significant interaction with genotype and age. Post-hoc analysis revealed that the latency was significantly shorter at 6-12 M than at 2-3 M in Ube3am-/p+ mice, and in Ube3am-/p+ mice than in WT mice at 6-12 M. No significant interaction or difference was observed by PTZ IP. CONCLUSION: The flurothyl-induced seizure paradigm revealed that seizure susceptibility of Ube3am-/p+ mice increased with age, similar to clinical studies reporting the reappearance of epilepsy in older age. The flurothyl-induced seizure paradigm applied to middle-aged Ube3am-/p+ mice could be a suitable protocol for screening drugs against seizures in AS.

Incidence of alveolar capillary dysplasia with misalignment of pulmonary veins in infants with unexplained severe pulmonary hypertension: The roles of clinical, pathological, and genetic testing.
Tetsuo Onda, Takuma Akimoto, Itaru Hayasaka, Masahiko Ikeda, Yuta Furuse, Akiko Ando, Yuichi Nakamura, Ryota Honjo, Atsushi Manabe, Itsuko Furuta, Kazutoshi Cho
Early human development, 155, 105323, 105323, 2021年04月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare and fatal disorder that occurs in the developing fetal lungs; at birth, infants exhibit an oxygenation disorder accompanied by severe pulmonary hypertension (PH) and have a very short life span. ACDMPV is definitively diagnosed by pathological findings, and infants born with unexplained severe PH may not be properly diagnosed without a biopsy or autopsy. METHODS: Japanese infants with unexplained severe PH were enrolled in this study. Genetic analyses were performed on DNA extracted from peripheral blood leukocytes. Sanger sequencing or next-generation sequencing was performed by coding exons and introns for FOXF1 in all samples. For individuals without pathogenic exonic variants, multiplex ligation-dependent probe amplification was performed to identify copy number variations (CNVs) in exons, introns, and in the upstream region of FOXF1. RESULTS: This study included 30 infants who were diagnosed over the course of nine years. Four individuals had the pathogenic variations on the exon 1 of FOXF1, including two frameshift and two missense variations. Pathogenic CNVs were found in another five individuals. CONCLUSION: In the pathologically proven ACDMPV patients, the ratios of cases with exonic variations, CNVs, and no genetic findings were reported as 45%, 45% and 10%, respectively. We estimate that about 30% (10 (9 + 1) out of 30) of individuals with unexplained severe PH had ACDMPV.

High-grade neuroepithelial tumor with BCL6 corepressor-alteration presenting pathological and radiological calcification: A case report.
Yukitomo Ishi, Ai Shimizu, Emi Takakuwa, Minako Sugiyama, Michinari Okamoto, Hiroaki Motegi, Shinsuke Hirabayashi, Yuko Cho, Akihiro Iguchi, Atsushi Manabe, Sumihito Nobusawa, Shinya Tanaka, Shigeru Yamaguchi
Pathology international, 71, 5, 348, 354, 2021年03月13日, ［国際誌］
英語, A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.

Clinical characteristics and outcomes of B-ALL with ZNF384 rearrangements: a retrospective analysis by the Ponte di Legno Childhood ALL Working Group.
Shinsuke Hirabayashi, Ellie R Butler, Kentaro Ohki, Nobutaka Kiyokawa, Anke K Bergmann, Anja Möricke, Judith M Boer, Hélène Cavé, Giovanni Cazzaniga, Allen Eng Juh Yeoh, Masashi Sanada, Toshihiko Imamura, Hiroto Inaba, Charles Mullighan, Mignon L Loh, Ulrika Norén-Nyström, Agata Pastorczak, Lee-Yung Shih, Marketa Zaliova, Ching-Hon Pui, Oskar A Haas, Christine J Harrison, Anthony V Moorman, Atsushi Manabe
Leukemia, 35, 11, 3272, 3277, 2021年03月10日, ［国際誌］
英語, 研究論文（学術雑誌）

In-Hospital Management Might Reduce Induction Deaths in Pediatric Patients With Acute Lymphoblastic Leukemia: Results From a Japanese Cohort.
Shunsuke Nakagawa, Motohiro Kato, Toshihiko Imamura, Chihaya Imai, Katsuyoshi Koh, Yoshifumi Kawano, Yasuto Shimomura, Arata Watanabe, Atsushi Kikuta, Akiko Saito, Keizo Horibe, Atsushi Manabe, Akira Ohara, Yasuhiro Okamoto
Journal of pediatric hematology/oncology, 43, 2, 39, 46, 2021年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications. We retrospectively analyzed the incidence of ID among children with ALL enrolled in 4 Japanese study groups between 1994 and 2013. Among 5620 children, 41 (0.73%) cases of ID were noted. The median age was 6.5 years; 24 children were female, and 7 had T-cell ALL. Infection was the most common cause of ID (n=22), but the incidence (0.39%) was lower than that reported in western countries. Mortality within 48 hours from the onset of infection was low, comprising 25% of infection-related deaths. The incidence of infections caused by Bacillus species was low. Only 1 patient died because of Aspergillus infection. Fatal infections mostly occurred during the third week of induction therapy. Our findings suggest that close monitoring, stringent infection control, and immediate administration of appropriate antibiotics through hospitalization might be important strategies in reducing the rate of infection-related ID in pediatric patients with ALL.

生後早期に血管内塞栓術を施行したガレン大静脈瘤の早産児例　　　　　　　　　　　　　　　
本庄 遼太, 中村 雄一, 安藤 明子, 恩田 哲雄, 古瀬 優太, 長 和俊, 武田 充人, 真部 淳
日本小児科学会雑誌, 125, 2, 348, 348, (公社)日本小児科学会, 2021年02月
日本語

先天性心疾患術後から乳び胸管理に難渋しリンパ管造影を実施したヌーナン症候群の乳児例　　　　　　　　　　　　　　　
佐藤 逸美, 白石 真大, 佐々木 大輔, 永井 礼子, 泉 岳, 山澤 弘州, 武田 充人, 真部 淳
日本小児科学会雑誌, 125, 2, 318, 318, (公社)日本小児科学会, 2021年02月
日本語

Ruxolitinib for hematopoietic cell transplantation-associated hemophagocytic lymphohistiocytosis.
Rintaro Ono, Miho Ashiarai, Shinsuke Hirabayashi, Kazuyoshi Mizuki, Yosuke Hosoya, Hiroki Yoshihara, Junya Ohtake, Shinichiro Mori, Atsushi Manabe, Daisuke Hasegawa
International journal of hematology, 113, 2, 297, 301, 2021年02月, ［国内誌］
英語, 研究論文（学術雑誌）, Hemophagocytic lymphohistiocytosis (HLH) is a severe complication after allogeneic hematopoietic cell transplantation (HCT) and can cause graft failure or multi-organ failure. Here, we report two children with refractory HCT-associated HLH treated with ruxolitinib. In the first patient, ruxolitinib resolved fever, cytopenia and hyperferritinemia. In another patient, although severe hepatic failure, which developed and worsened before the administration of ruxolitinib, was irreversible, rapid improvement in fever, leukopenia and hyperferritinemia was observed. Of note, multiplex cytokine profiling showed amelioration of cytokine storm in both patients. Ruxolitinib may be an encouraging option for HCT-associated HLH.

Acquisition of monosomy 7 and a RUNX1 mutation in Pearson syndrome.
Akira Nishimura, Shinsuke Hirabayashi, Daisuke Hasegawa, Kenichi Yoshida, Yuichi Shiraishi, Miho Ashiarai, Yosuke Hosoya, Tohru Fujiwara, Hideo Harigae, Satoru Miyano, Seishi Ogawa, Atsushi Manabe
Pediatric blood & cancer, 68, 2, e28799, 2021年02月, ［国際誌］
英語, 研究論文（学術雑誌）, Pearson syndrome (PS) is a very rare and often fatal multisystem disease caused by deletions in mitochondrial DNA that result in sideroblastic anemia, vacuolization of marrow precursors, and pancreatic dysfunction. Spontaneous recovery from anemia is often observed within several years of diagnosis. We present the case of a 4-month-old male diagnosed with PS who experienced prolonged severe pancytopenia preceding the emergence of monosomy 7. Whole-exome sequencing identified two somatic mutations, including RUNX1 p.S100F that was previously reported as associated with myeloid malignancies. The molecular defects associated with PS may have the potential to progress to advanced myelodysplastic syndrome .

Correction to: FLEND (nelarabine, fludarabine, and etoposide) for relapsed T-cell acute lymphoblastic leukemia in children: a report from Japan Children's Cancer Group.
Tadashi Kumamoto, Hiroaki Goto, Chitose Ogawa, Toshinori Hori, Takao Deguchi, Takuya Araki, Akiko M Saito, Atsushi Manabe, Keizo Horibe, Hidemi Toyoda
International journal of hematology, 113, 2, 308, 309, 2021年02月, ［国内誌］
英語

An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia.
Yoichi Tanaka, Allen Eng Juh Yeoh, Takaya Moriyama, Chi-Kong Li, Ko Kudo, Yuki Arakawa, Jassada Buaboonnam, Hui Zhang, Hsi-Che Liu, Hany Ariffin, Zhiwei Chen, Shirley K Y Kham, Rina Nishii, Daisuke Hasegawa, Junya Fujimura, Dai Keino, Kensuke Kondoh, Atsushi Sato, Takahiro Ueda, Masaki Yamamoto, Yuichi Taneyama, Moeko Hino, Masatoshi Takagi, Akira Ohara, Etsuro Ito, Katsuyoshi Koh, Hiroki Hori, Atsushi Manabe, Jun J Yang, Motohiro Kato
Haematologica, 106, 7, 2026, 2029, 2021年01月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Not available.

Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants.
Ayumu Arakawa, Hitoshi Ichikawa, Takashi Kubo, Noriko Motoi, Tadashi Kumamoto, Miho Nakajima, Kan Yonemori, Emi Noguchi, Kuniko Sunami, Kouya Shiraishi, Hiroki Kakishima, Hiroshi Yoshida, Tomoro Hishiki, Naonori Kawakubo, Takafumi Kuroda, Takako Kiyokawa, Kyosuke Yamada, Nozomu Yanaihara, Kazuaki Takahashi, Aikou Okamoto, Shinsuke Hirabayashi, Daisuke Hasegawa, Atsushi Manabe, Kentaro Ono, Masaki Matsuoka, Yasuhito Arai, Yosuke Togashi, Tatsuhiro Shibata, Hiroyoshi Nishikawa, Kazunori Aoki, Noboru Yamamoto, Takashi Kohno, Chitose Ogawa
The New England journal of medicine, 384, 1, 42, 50, 2021年01月07日, ［国際誌］
英語, 研究論文（学術雑誌）, Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).

Diagnostic Capability of Cerebrospinal Fluid-Placental Alkaline Phosphatase Value in Intracranial Germ Cell Tumor.
Michinari Okamoto, Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Takashi Mori, Takayuki Hashimoto, Yukayo Terashita, Shinsuke Hirabayashi, Minako Sugiyama, Akihiro Iguchi, Yuko Cho, Atsushi Manabe, Kiyohiro Houkin
Oncology, 99, 1, 23, 31, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Most types of intracranial germ cell tumors (IGCTs) are sensitive to chemoradiation. However, biopsy specimens are usually small and thus cannot be used for obtaining an accurate pathological diagnosis. Recently, the cerebrospinal fluid (CSF) placental alkaline phosphatase (PLAP) value has been considered a new biomarker of IGCTs. The present study aimed to evaluate the discriminatory characteristics of the CSF-PLAP value upon diagnosis and at the time of recurrence in patients with IGCTs. METHODS: Between 2015 and 2019, this study included 37 patients with tumors located in the intraventricular and/or periventricular region. The CSF-PLAP level was assessed before the patients received any treatment. The PLAP level was evaluated during and after first-line chemoradiotherapy in 7 patients with IGCTs. The CSF-PLAP values were compared according to histological diagnosis, and the correlation between these values and radiographical features was assessed. The CSF-PLAP values of 6 patients with IGCTs with suspected recurrence were evaluated based on neuroimaging findings. RESULTS: The CSF-PLAP values were significantly higher in patients with IGCTs than in those with other types of brain tumor (n = 19 vs. 18; median: 359.0 vs. <8.0 pg/mL). The specificity and sensitivity were 88 and 95%, respectively, with a cutoff value of 8.0 pg/mL. In patients with IGCT, the CSF-PLAP value was higher in patients with germinoma than in those with nongerminomatous germ cell tumors (n = 12 vs. 7; median: 415.0 vs. 359.0 pg/mL). Regarding the time course, the CSF-PLAP value decreased to below the detection limit after the reception of first-line chemoradiotherapy in all 7 patients. A significant correlation was observed between the initial CSF-PLAP value and the tumor reduction volume after receiving first-line chemoradiotherapy (p < 0.0003, R2 = 0.6165, logY = 1.202logX - 1.727). Among the patients with suspected IGCT recurrence (n = 6), the CSF-PLAP value was high in patients with recurrence (n = 3; median: 259.0 pg/mL), and that in patients (n = 3) without recurrence was below the lower detection limit. CONCLUSIONS: The CSF-PLAP level is a useful biomarker during the initial diagnosis of IGCTs and at the time of recurrence. It may be associated with the volume of germinomatous components of tumors.

CAN HIGH LEVEL SERUM HCG-B BE CONSIDERED EQUIVALENT TO A DIAGNOSIS OF CHORIOCARCINOMA IN PRIMARY CENTRAL NERVOUS SYSTEM GERM-CELL TUMOR?
Hiroaki Motegi, Shigeru Yamaguchi, Yukitomo Ishi, Michinari Okamoto, Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Atsushi Manabe, Kiyohiro Houkin
NEURO-ONCOLOGY, 22, 329, 330, OXFORD UNIV PRESS INC, 2020年12月, ［査読有り］
英語

当院の先天性門脈体循環シャント症例の臨床検討　　　　　　　　　　　　　　　
辻岡 孝郎, 泉 岳, 武田 充人, 小杉山 清隆, 山澤 弘州, 谷口 宏太, 永井 礼子, 本多 昌平, 阿保 大介, 川村 典生, 真部 淳
日本小児循環器学会雑誌, 36, Suppl.2, s2, 356, (NPO)日本小児循環器学会, 2020年11月
日本語

当院の先天性門脈体循環シャント症例の臨床検討　　　　　　　　　　　　　　　
辻岡 孝郎, 泉 岳, 武田 充人, 小杉山 清隆, 山澤 弘州, 谷口 宏太, 永井 礼子, 本多 昌平, 阿保 大介, 川村 典生, 真部 淳
日本小児循環器学会雑誌, 36, Suppl.2, s2, 356, (NPO)日本小児循環器学会, 2020年11月
日本語

FLEND (nelarabine, fludarabine, and etoposide) for relapsed T-cell acute lymphoblastic leukemia in children: a report from Japan Children's Cancer Group.
Tadashi Kumamoto, Hiroaki Goto, Chitose Ogawa, Toshinori Hori, Takao Deguchi, Takuya Araki, Akiko M Saito, Atsushi Manabe, Keizo Horibe, Hidemi Toyoda
International journal of hematology, 112, 5, 720, 724, 2020年11月, ［国内誌］
英語, 研究論文（学術雑誌）, Nelarabine is a key drug for T-cell acute lymphoblastic leukemia (T-ALL). Fludarabine and etoposide might have synergistic effect with nelarabine by inhibiting ribonucleotide reductase and by preparing cell cycle for G1/S phase, respectively. We had started phase 1/2 multicenter clinical trial of combination chemotherapy consisted of nelarabine, fludarabine, and etoposide (FLEND therapy) for children with relapsed/refractory T-ALL which has been conducted since October 2011. Although we could not complete this trial because of recruitment difficulties, we treated five children with first-relapsed T-ALL which were enrolled in the phase 1 dose escalation study of fludarabine and etoposide with nelarabine. No dose-limiting toxicity occurred, and frequent grade 3-4 toxicity was hematological toxicity and febrile neutropenia, as expected. There was no neurotoxicity. All 2 patients who received the target dose of FLEND, in which nelarabine (650 mg/m2), fludarabine (30 mg/m2), and etoposide (100 mg/m2) were administered for 5 consecutive days, were induced to complete remission. We concluded that FLEND might be safe and one of the promising combination chemotherapies to relapsed/refractory T-ALL.

Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia.
Hiroo Ueno, Kenichi Yoshida, Yusuke Shiozawa, Yasuhito Nannya, Yuka Iijima-Yamashita, Nobutaka Kiyokawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tomoya Isobe, Masafumi Seki, Shunsuke Kimura, Hideki Makishima, Masahiro M Nakagawa, Nobuyuki Kakiuchi, Keisuke Kataoka, Tetsuichi Yoshizato, Dai Nishijima, Takao Deguchi, Kentaro Ohki, Atsushi Sato, Hiroyuki Takahashi, Yoshiko Hashii, Sadao Tokimasa, Junichi Hara, Yoshiyuki Kosaka, Koji Kato, Takeshi Inukai, Junko Takita, Toshihiko Imamura, Satoru Miyano, Atsushi Manabe, Keizo Horibe, Seishi Ogawa, Masashi Sanada
Blood advances, 4, 20, 5165, 5173, 2020年10月27日, ［国際誌］
英語, 研究論文（学術雑誌）, Recent genetic studies using high-throughput sequencing have disclosed genetic alterations in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, their effects on clinical outcomes have not been fully investigated. To address this, we comprehensively examined genetic alterations and their prognostic impact in a large series of pediatric B-ALL cases. We performed targeted capture sequencing in a total of 1003 pediatric patients with B-ALL from 2 Japanese cohorts. Transcriptome sequencing (n = 116) and/or array-based gene expression analysis (n = 120) were also performed in 203 (84%) of 243 patients who were not categorized into any disease subgroup by panel sequencing or routine reverse transcription polymerase chain reaction analysis for major fusions in B-ALL. Our panel sequencing identified novel recurrent mutations in 2 genes (CCND3 and CIC), and both had positive correlations with ETV6-RUNX1 and hypodiploid ALL, respectively. In addition, positive correlations were also newly reported between TCF3-PBX1 ALL with PHF6 mutations. In multivariate Cox proportional hazards regression models for overall survival, TP53 mutation/deletion, hypodiploid, and MEF2D fusions were selected in both cohorts. For TP53 mutations, the negative effect on overall survival was confirmed in an independent external cohort (n = 466). TP53 mutation was frequently found in IGH-DUX4 (5 of 57 [9%]) ALL, with 4 cases having 17p LOH and negatively affecting overall survival therein, whereas TP53 mutation was not associated with poor outcomes among NCI (National Cancer Institute) standard risk (SR) patients. A conventional treatment approach might be enough, and further treatment intensification might not be necessary, for patients with TP53 mutations if they are categorized into NCI SR.

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial.
Daisuke Tomizawa, Takako Miyamura, Toshihiko Imamura, Tomoyuki Watanabe, Akiko Moriya Saito, Atsushi Ogawa, Yoshihiro Takahashi, Masahiro Hirayama, Tomohiko Taki, Takao Deguchi, Toshinori Hori, Masashi Sanada, Shigeru Ohmori, Masami Haba, Akihiro Iguchi, Yuki Arakawa, Yuhki Koga, Atsushi Manabe, Keizo Horibe, Eiichi Ishii, Katsuyoshi Koh
Blood, 136, 16, 1813, 1823, 2020年10月15日, ［国際誌］
英語, 研究論文（学術雑誌）, The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children's Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n = 15), IR (n = 19), or HR (n = 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ≥0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

下垂体単独ランゲルハンス細胞組織球症の一例　　　　　　　　　　　　　　　
渡邊 敏史, 平林 真介, 原 和也, 杉山 未奈子, 長 祐子, 高桑 恵美, 茂木 洋晃, 山口 秀, 井口 晶裕, 真部 淳
日本小児血液・がん学会雑誌, 57, 4, 306, 306, (一社)日本小児血液・がん学会, 2020年10月
日本語

カテコラミン過剰分泌による症状を呈した神経芽腫の2例
中山 加奈子, 中村 明枝, 橋本 佳帆子, 鎌田 瑛理, 菱村 希, 山口 健史, 井口 晶裕, 本多 昌平, 木田 毅, 真部 淳
日本内分泌学会雑誌, 96, 2, 552, 552, (一社)日本内分泌学会, 2020年10月
日本語

AYA世代小児がん経験者における口腔内状態と晩期合併症の検討　　　　　　　　　　　　　　　
細谷 要介, 宇治川 清登, 長谷川 大輔, 鈴木 優里, 小林 京子, 真部 淳, 石田 也寸志, 小澤 靖弘, 小澤 美和
日本小児血液・がん学会雑誌, 57, 4, 276, 276, (一社)日本小児血液・がん学会, 2020年10月
日本語

小児がん経験者の就労状況への関連要因の探索　　　　　　　　　　　　　　　
小林 京子, 石田 也寸志, 小澤 美和, 郡司 美千代, 細谷 要介, 長谷川 大輔, 真部 淳
日本小児血液・がん学会雑誌, 57, 4, 380, 380, (一社)日本小児血液・がん学会, 2020年10月
日本語

Onset mechanism of a female patient with Dent disease 2.
Takayuki Okamoto, Nana Sakakibara, Kandai Nozu, Toshiyuki Takahashi, Asako Hayashi, Yasuyuki Sato, China Nagano, Masafumi Matsuo, Kazumoto Iijima, Atsushi Manabe
Clinical and experimental nephrology, 24, 10, 946, 954, 2020年10月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Approximately 15% of patients with Dent disease have pathogenic variants in the OCRL gene on Xq25-26, a condition that is referred to as Dent disease 2 (Dent-2). Dent-2 patients sometimes show mild extrarenal features of Lowe syndrome, such as mild mental retardation, suggesting that Dent-2 represents a mild form of Lowe syndrome. To date, eight female patients with Lowe syndrome have been reported, but no female Dent-2 patients have been reported. METHODS: In this study, we performed genetic testing of the first female Dent-2 patient to detect the presence of an OCRL variant. Aberrant splicing was demonstrated by in vivo, in vitro, and in silico assays, and skewed X-chromosome inactivation (XCI) in our patient and asymptomatic mothers of three Lowe patients with the heterozygous OCRL variant was evaluated by HUMARA assays using genomic DNA and RNA expression analysis. RESULTS: Our patient had an OCRL heterozygous intronic variant of c.1603-3G > C in intron 15 that led to a 169-bp insertion in exon 16, yielding the truncating mutation r.1602_1603ins (169) (p.Val535Glyfs*6) in exon 16. HUMARA assays of leukocytes obtained from this patient demonstrated incompletely skewed XCI (not extremely skewed). On the other hand, the asymptomatic mothers of 3 Lowe patients demonstrated random XCI. These results may lead to our patient's Dent-2 phenotype. CONCLUSIONS: This is the first report of a female patient clinically and genetically diagnosed with Dent-2 caused by an OCRL heterozygous splicing site variant and skewed XCI. Skewed XCI may be one of the factors associated with phenotypic diversity in female patients with Lowe syndrome and Dent-2.

Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L04-16.
Kentaro Ohki, Hiroyuki Takahashi, Takashi Fukushima, Toru Nanmoku, Shinpei Kusano, Makiko Mori, Yozo Nakazawa, Yuki Yuza, Masahiro Migita, Haruna Okuno, Akira Morimoto, Hiroshi Yoshino, Motohiro Kato, Yasuhide Hayashi, Atsushi Manabe, Akira Ohara, Daisuke Hasegawa, Takeshi Inukai, Daisuke Tomizawa, Katsuyoshi Koh, Nobutaka Kiyokawa
Genes, chromosomes & cancer, 59, 10, 551, 561, 2020年10月, ［国際誌］
英語, 研究論文（学術雑誌）, Immunophenotyping was performed in 1044 consecutive childhood acute lymphoblastic leukemia (ALL) patients enrolled in the Tokyo Children's Cancer Study Group L04-16 trial, revealing novel findings associated with genetic abnormalities. In addition to TCF3-PBX1 and MEF2D fusions, the CD10(+) subtype of KMT2A-MLLT3-positive ALL frequently exhibited the cytoplasmic-μ(+) pre-B ALL immunophenotype. Although ETV6-RUNX1 was significantly correlated with myeloid antigen expression, more than half of patients expressed neither CD33 nor CD13, while the CD27(+) /CD44(-) immunophenotype was maintained. Expression of CD117 and CD56 in B-cell precursor-ALL was limited to certain subtypes including ETV6-RUNX1 and KMT2A-MLLT3. Besides BCR-ABL1, CRLF2, hyperdiploidy, and hypodiploidy, CD66c was also expressed in Ph-like kinase fusion-, PAX5 fusion-, and DUX4 fusion-positive ALL, but not in MEF2D fusion-positive ALL, indicating constant selectivity of CD66c expression. In T-ALL, SIL-TAL1-positive patients were likely to exhibit a more mature immunophenotype. Expression of CD21 and CD10 was not rare in T-ALL, while lack of CD28 was an additional feature of early T-cell precursor-ALL. Considering the immunophenotype as a prognostic maker, MEF2D fusion-positive ALL with CD5 expression may be associated with a poorer prognosis in comparison with those lacking CD5 expression. In cases with characteristic marker expression, the presence of certain fusion transcripts could be predicted accurately.

Clinical utility of target capture-based panel sequencing in hematological malignancies: A multicenter feasibility study.
Takahiko Yasuda, Masashi Sanada, Dai Nishijima, Takashi Kanamori, Yuka Iijima, Hiroyoshi Hattori, Akiko Saito, Hiroaki Miyoshi, Yuichi Ishikawa, Norio Asou, Kensuke Usuki, Shinsuke Hirabayashi, Motohiro Kato, Masaki Ri, Hiroshi Handa, Tadao Ishida, Hirohiko Shibayama, Masahiro Abe, Chisako Iriyama, Kennosuke Karube, Momoko Nishikori, Koichi Ohshima, Keisuke Kataoka, Kenichi Yoshida, Yuichi Shiraishi, Hiroaki Goto, Souichi Adachi, Ryoji Kobayashi, Hitoshi Kiyoi, Yasushi Miyazaki, Seishi Ogawa, Hiroki Kurahashi, Hisayuki Yokoyama, Atsushi Manabe, Shinsuke Iida, Akihiro Tomita, Keizo Horibe
Cancer science, 111, 9, 3367, 3378, 2020年09月, ［国際誌］
英語, 研究論文（学術雑誌）, Although next-generation sequencing-based panel testing is well practiced in the field of cancer medicine for the identification of target molecules in solid tumors, the clinical utility and clinical issues surrounding panel testing in hematological malignancies have yet to be fully evaluated. We conducted a multicenter prospective clinical sequencing study to verify the feasibility of a panel test for hematological tumors, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, and diffuse large B-cell lymphoma. Out of 96 eligible patients, 79 patients (82%) showed potentially actionable findings, based on the clinical sequencing assays. We identified that genetic alterations with a strong clinical significance were found at a higher frequency in terms of diagnosis (n = 60; 63%) and prognosis (n = 61; 64%) than in terms of therapy (n = 8; 8%). Three patients who harbored a germline mutation in either DDX41 (n = 2) or BRCA2 (n = 1) were provided with genetic counseling. At 6 mo after sequencing, clinical actions based on the diagnostic (n = 5) or prognostic (n = 3) findings were reported, but no patients were enrolled in a clinical trial or received targeted therapies based on the sequencing results. These results suggest that panel testing for hematological malignancies would be feasible given the availability of useful diagnostic and prognostic information. This study is registered with the UMIN Clinical Trial Registry (UMIN000029879, multiple myeloma; UMIN000031343, adult acute myeloid leukemia; UMIN000033144, diffuse large B-cell lymphoma; and UMIN000034243, childhood leukemia).

Statement on the prevention and treatment of COVID-19 in patients with pediatric cancer in Japan.
Tomoko Iehara, Atsushi Manabe, Hajime Hosoi
Pediatric blood & cancer, 67, 9, e28440, 2020年09月, ［国際誌］
英語

Pulmonary vasodilators can lead to various complications in pulmonary "arterial" hypertension associated with congenital heart disease.
Ayako Chida-Nagai, Koichi Sagawa, Takao Tsujioka, Takanori Fujimoto, Kota Taniguchi, Osamu Sasaki, Gaku Izumi, Hirokuni Yamazawa, Naoki Masaki, Atsushi Manabe, Atsuhito Takeda
Heart and vessels, 35, 9, 1307, 1315, 2020年09月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.

Comparison of child and family reports of health-related quality of life in pediatric acute lymphoblastic leukemia patients after induction therapy.
Shohei Nakajima, Iori Sato, Takafumi Soejima, Katsuyoshi Koh, Motohiro Kato, Yasuhiro Okamoto, Toshihiko Imamura, Miho Maeda, Yasushi Ishida, Atsushi Manabe, Kiyoko Kamibeppu
BMC pediatrics, 20, 1, 390, 390, 2020年08月19日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: This study aims at determining the health-related quality of life (HRQOL) of children with acute lymphoblastic leukemia (ALL) after the induction therapy, assessing the agreement between child self-reports and family proxy-reports HRQOL, and determining the factors related to this agreement, especially child age, family attendance, and children's social relationships beyond the family. METHODS: We analyzed questionnaire data (2012-2017) from the Japanese Pediatric Leukemia/Lymphoma Study Group's clinical study (ALL-B12). Participants were children with B-cell precursor ALL aged 5-18 and their family members, who mostly took care of the child during hospitalization. Participants answered the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales (PedsQL-G), and Cancer Module (PedsQL-C) to measure pediatric HRQOL. We calculated the differences between child self-reported and family proxy-reported subscale scores along with intraclass correlation coefficients (ICC). We conducted multiple regression analyses according to all participant pairs and age groups (young children, school age, and adolescents), with ICCs for all PedsQL-G subscales (ICC-G) and all PedsQL-C subscales (ICC-C) as the outcome variables. RESULTS: Five hundred twenty-two pairs of children and their families were analyzed. We observed a moderate level of agreement on most PedsQL subscales between child self-reports and family proxy-reports; however, worry had the weakest agreement for all PedsQL subscales (ICC = .32, 95% confidence interval = .24-.40). The agreement of ICC-C was positively related to family attendance in the hospitalization, only for the young children group (B = .185, p = .003). CONCLUSIONS: We observed some differences between child self-reports and family proxy-reports of HRQOL of children with ALL. Both child self-reports and family proxy-reports captured HRQOL in the induction therapy. We suggest that attending to young children's hospitalization affects the level of agreement between reports on their HRQOL.

Clinical features of children with polycythemia vera, essential thrombocythemia, and primary myelofibrosis in Japan: A retrospective nationwide survey
Hisashi Ishida, Yuji Miyajima, Nobuyuki Hyakuna, Satoru Hamada, Takeo Sarashina, Risa Matsumura, Katsutsugu Umeda, Tetsuo Mitsui, Naoto Fujita, Daisuke Tomizawa, Kevin Y. Urayama, Yasushi Ishida, Takashi Taga, Masatoshi Takagi, Souichi Adachi, Atsushi Manabe, Toshihiko Imamura, Katsuyoshi Koh, Akira Shimada
eJHaem, 1, 1, 86, 93, Wiley, 2020年07月
研究論文（学術雑誌）

カテコラミン過剰に伴う症状を契機に診断に至った神経芽腫の1例　　　　　　　　　　　　　　　
橋本 佳帆子, 中山 加奈子, 山口 健史, 原 和也, 寺下 友佳代, 杉山 未奈子, 長 祐子, 井口 晶裕, 本多 昌平, 中村 明枝, 真部 淳
日本小児科学会雑誌, 124, 7, 1156, 1156, (公社)日本小児科学会, 2020年07月
日本語

Nationwide study of pediatric B-cell precursor acute lymphoblastic leukemia with chromosome 8q24/MYC rearrangement in Japan.
Kimiyoshi Sakaguchi, Toshihiko Imamura, Sae Ishimaru, Chihaya Imai, Hidemi Shimonodan, Naoto Fujita, Keiko Okada, Takeshi Taketani, Rie Kanai, Hisamichi Tauchi, Motohiro Kato, Yasuko Kojima, Arata Watanabe, Takao Deguchi, Yoshiko Hashii, Nobutaka Kiyokawa, Tomohiko Taki, Akiko M Saito, Keizo Horibe, Atsushi Manabe, Atsushi Sato, Katsuyoshi Koh
Pediatric blood & cancer, 67, 7, e28341, 2020年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Rearrangements of chromosome 8q24/MYC (8q24/MYC-r), resulting from t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11), are mainly associated with Burkitt lymphoma/leukemia (BL) and rarely observed in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The characteristics of BCP-ALL with 8q24/MYC-r are poorly understood. PROCEDURE: A retrospective nationwide study of data from patients with pediatric BCP-ALL with 8q24/MYC-r in Japan was conducted to clarify the clinical and biological characteristics associated with 8q24/MYC-r BCP-ALL. RESULTS: Ten patients with BCP-ALL with 8q24/MYC-r, including three with double-hit leukemia (DHL) (two with t(8;14)(q24;q32) and t(14;18)(q32;q21) and one with t(8;14) and t(3;22)(q27;q11)), were identified. Patients with BCP-ALL with 8q24/MYC-r had higher median age and uric acid and lactate dehydrogenase levels, than those without 8q24/MYC-r. All patients were initially treated with ALL-type chemotherapy; however, four, including one with DHL, were switched to BL-type chemotherapy, based on cytogenetic findings. One patient relapsed after standard-risk ALL-type chemotherapy, and two patients with DHL did not attain complete remission with chemotherapy; all three died within 11 months. The other seven patients treated with BL-type or high-risk ALL-type chemotherapy are alive without disease. CONCLUSIONS: The clinical and laboratory features of BL with IG-MYC rearrangement, displaying a BCP immunophenotype (Wagener et al. and Herbrueggen et al. termed it as pre-BLL), are similar to those of BCP-ALL with 8q24/MYC-r. Low-risk ALL-type chemotherapy may not be appropriate for them, and further studies are required to establish an adequate therapeutic strategy. Further studies of DHL to identify new treatment strategies are also needed.

Refractory malignant hepatocellular tumor consisting of hepatocellular carcinoma and hepatoblastoma in a 10-year-old male
Minako Sugiyama, Shinsuke Hirabayashi, Yukayo Terashita, Yuko Cho, Akihiro Iguchi, Yoshihito Ohhara, Daisuke Abo, Shohei Honda, Emi Takakuwa, Atsushi Manabe
Authorea, Inc., 2020年06月22日

Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment.
Ondrej Hrusak, Tomas Kalina, Joshua Wolf, Adriana Balduzzi, Massimo Provenzi, Carmelo Rizzari, Susana Rives, María Del Pozo Carlavilla, Maria E V Alonso, Nerea Domínguez-Pinilla, Jean-Pierre Bourquin, Kjeld Schmiegelow, Andishe Attarbaschi, Pernilla Grillner, Karin Mellgren, Jutte van der Werff Ten Bosch, Rob Pieters, Triantafyllia Brozou, Arndt Borkhardt, Gabriele Escherich, Melchior Lauten, Martin Stanulla, Owen Smith, Allen E J Yeoh, Sarah Elitzur, Ajay Vora, Chi-Kong Li, Hany Ariffin, Alexandra Kolenova, Luciano Dallapozza, Roula Farah, Jelena Lazic, Atsushi Manabe, Jan Styczynski, Gabor Kovacs, Gabor Ottoffy, Maria S Felice, Barbara Buldini, Valentino Conter, Jan Stary, Martin Schrappe
European journal of cancer (Oxford, England : 1990), 132, 11, 16, 2020年06月, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

131 I-MIBG therapy with WT-1 peptide for refractory neuroblastoma.
Minako Sugiyama, Kinuya Seigo, Yosuke Hosoya, Akihiro Iguchi, Atsushi Manabe
Pediatrics international : official journal of the Japan Pediatric Society, 62, 6, 746, 747, 2020年06月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Successful treatment of dumbbell-shaped Hodgkin lymphoma with massive sacral bone destruction.
Minako Sugiyama, Yukayo Terashita, Yuko Cho, Akihiro Iguchi, Ryuta Arai, Emi Takakuwa, Shohei Honda, Atsushi Manabe
Pediatric blood & cancer, 67, 5, e28210, 2020年05月, ［査読有り］, ［国際誌］
英語

Nationwide epidemiological survey of familial myelodysplastic syndromes/acute myeloid leukemia in Japan: a multicenter retrospective study.
Kensuke Takaoka, Junji Koya, Akihide Yoshimi, Takashi Toya, Takashi Kobayashi, Yasuhito Nannya, Kumi Nakazaki, Shunya Arai, Hironori Ueno, Kensuke Usuki, Takeshi Yamashita, Daisuke Imanishi, Shinya Sato, Kenshi Suzuki, Hironori Harada, Atsushi Manabe, Yasuhide Hayashi, Yasushi Miyazaki, Mineo Kurokawa
Leukemia & lymphoma, 61, 7, 1, 7, 2020年03月11日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Although several pedigrees of familial myelodysplastic syndromes/acute myeloid leukemia (fMDS/AML) have been reported, the epidemiology and clinical features has been poorly understood. To explore the epidemiology of this entity, we performed a retrospective nationwide epidemiological survey in Japan using questionnaire sheets. The questionnaire was sent to 561 institutions or hospitals certified by Japanese Society of Hematology, unearthing the existence of 41 pedigrees of fMDS/AML. Among them, we obtained the clinical information of 31 patients in 20 pedigrees. The median age of the initial diagnosis was 51 years (range 9-88 years) and the WHO classification 2008 ranged from refractory anemia (RA) to AML. Focusing on the familial MDS patients, refractory anemia with excess blasts (RAEB)-2 was the largest group (27.3%). The median overall survival (OS) of fMDS and fAML in this study were 71.6 and 12.4 months, and the five-year OS were 61.3 and 50%, respectively.

病棟でアデノウイルスによる感染性胃腸炎が発生した際の伝播防止対策に関する検討　　　　　　　　　　　　　　　
石黒 信久, 長 祐子, 井口 晶裕, 杉山 未奈子, 寺下 友佳代, 武田 充人, 真部 淳
日本小児科学会雑誌, 124, 2, 486, 486, (公社)日本小児科学会, 2020年02月
日本語

当科における尿細管間質性腎炎ぶどう膜炎症候群症例の臨床的特徴　　　　　　　　　　　　　　　
林 麻子, 佐藤 泰征, 高橋 俊行, 上田 泰弘, 真部 淳, 岡本 孝之
日本小児科学会雑誌, 124, 2, 272, 272, (公社)日本小児科学会, 2020年02月
日本語

当院で管理中の先天性門脈体循環シャント6例の検討　　　　　　　　　　　　　　　
辻岡 孝郎, 泉 岳, 武田 充人, 小杉山 清隆, 山澤 弘州, 阿部 二郎, 谷口 宏太, 佐々木 大輔, 永井 礼子, 本多 昌平, 荒 桃子, 阿保 大介, 曽山 武士, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 神山 俊哉, 武冨 紹信, 真部 淳
日本小児科学会雑誌, 124, 2, 250, 250, (公社)日本小児科学会, 2020年02月
日本語

当院で管理中の先天性門脈体循環シャント6例の検討　　　　　　　　　　　　　　　
辻岡 孝郎, 泉 岳, 武田 充人, 小杉山 清隆, 山澤 弘州, 阿部 二郎, 谷口 宏太, 佐々木 大輔, 永井 礼子, 本多 昌平, 荒 桃子, 阿保 大介, 曽山 武士, 川村 典生, 渡辺 正明, 後藤 了一, 嶋村 剛, 神山 俊哉, 武冨 紹信, 真部 淳
日本小児科学会雑誌, 124, 2, 250, 250, (公社)日本小児科学会, 2020年02月
日本語

小児科スタッフが中高生以上のがん患者と関わる上で抱えている課題に関する質問紙調査
半谷 まゆみ, 関 正史, 三谷 友一, 樋渡 光輝, 岩崎 美和, 木村 敬子, 副島 尭史, 佐藤 伊織, 松本 公一, 康 勝好, 真部 淳, 高木 正稔, 藤村 純也, 滝田 順子
日本小児血液・がん学会雑誌, 56, 5, 447, 453, (一社)日本小児血液・がん学会, 2020年02月, ［査読有り］
日本語, 【背景】白血病を中心に、思春期・若年成人(Adolescents and Young Adults;AYA)世代のがん治療における小児科の優位性が示されてきたことに伴い、小児期と成人期の間にあたる彼らが小児科で治療される機会は増えてきている。しかし、この年代の患者と関わる上で小児科スタッフが抱える問題について、まとまった報告はない。【目的】中高生以上のがん患者と関わる小児科スタッフたちの現状を把握し、課題を整理する。【方法】総合病院小児科あるいは小児専門病院、計6施設で、中高生以上のがん患者と日常的に関わる機会のある多職種スタッフ(医師、看護師、薬剤師、院内学級教師など)を対象として、中高生以上のがん患者との関わり等について質問紙調査を実施した。【結果】計93名のスタッフから回答を得た。医師よりも他職種のほうが患者との関わり方に難しさを実感しており、特に心の問題やライフイベントに関する問題が難しいと回答した者が多かった。また、妊孕性に関する説明は施設間で勧奨度に相違があった。【結語】中高生以上のがん患者を小児科で診療する上で、病院スタッフが様々な問題を抱えていることが分かった。今後小児科で思春期・若年成人世代のがん患者の診療機会が増加することが見込まれる中、多職種・多施設間での更なる情報共有により、患者が安心して闘病生活を送れるよう心理社会的課題などに対するサポート体制の充実が望まれる。(著者抄録)

Immune thrombocytopenia in a case of trisomy 18
Minako Sugiyama, Yukayo Terashita, Atsuhito Takeda, Akihiro Iguchi, Atsushi Manabe
PEDIATRICS INTERNATIONAL, 62, 2, 240, 242, WILEY, 2020年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Relationship between Sedative Antihistamines and the Duration of Febrile Seizures.
Atsuro Daida, Gaku Yamanaka, Shin-Ichi Tsujimoto, Mina Yokoyama, Kuniyoshi Hayashi, Kevin Y Urayama, Yasushi Ishida, Atsushi Manabe, Isao Kusakawa, Masaaki Ogihara, Hisashi Kawashima
Neuropediatrics, 51, 2, 154, 159, 2020年01月14日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Some studies have shown that sedative antihistamines prolong febrile seizure duration. Although the collective evidence is still mixed, the Japanese Society of Child Neurology released guidelines in 2015 that contraindicated the use of sedative antihistamines in patients with febrile seizure. Focused on addressing limitations of previous studies, we conducted a cross-sectional study to evaluate the relationship between febrile seizure duration and the use of sedative antihistamines. Data were collected from patients who visited St. Luke's International Hospital due to febrile seizure between August 2013 and February 2016. Patients were divided into groups based on their prescribed medications: sedative antihistamine, nonsedative antihistamine, and no antihistamine. Seizure duration was the primary outcome and was examined using multivariate analyses. Of the 426 patients included, sedative antihistamines were administered to 24 patients. The median seizure duration was approximately 3 minutes in all three groups. There was no statistical difference in the bivariate (p = 0.422) or multivariate analyses (p = 0.544). Our results do not support the relationship between sedative antihistamine use and prolonged duration of febrile seizure. These results suggest that the use of antihistamines may be considered for patients with past history of febrile seizure, when appropriate.

褐色細胞腫との鑑別を要した神経芽腫の2歳女児例
山口 健史, 中村 明枝, 中山 加奈子, 菱村 希, 橋本 佳帆子, 長 祐子, 本多 昌平, 真部 淳
日本内分泌学会雑誌, 95, 3, 873, 873, (一社)日本内分泌学会, 2020年01月
日本語

Corticosteroid-induced glaucoma in pediatric patients with hematological malignancies.
Minako Sugiyama, Yukayo Terashita, Kazuya Hara, Yuko Cho, Akihiro Iguchi, Shinki Chin, Atsushi Manabe
Pediatric blood & cancer, 66, 12, e27977, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Corticosteroids, especially dexamethasone, play a critical role in chemotherapy for pediatric hematological malignancies. We previously observed that patients with complaints of headache or photophobia during corticosteroid administration had high intraocular pressure (IOP). PROCEDURE: We measured IOP during corticosteroid administration in 15 patients with acute leukemia or lymphoma undergoing treatment at our institution from January 2016 to December 2018. IOP was measured by an ophthalmologist within seven days of the initiation of standard dose of corticosteroid, which was defined as 60 mg/m2 /day for prednisolone and 10 mg/m2 /day for dexamethasone. RESULTS: Fifteen patients received 52 courses of chemotherapy containing corticosteroids. IOP exceeded 21 mmHg among 13 patients in 28 courses. Twelve of the 13 patients were administered topical treatment, and six of the 12 patients needed additional diuretic agents. IOP during the chemotherapy courses containing dexamethasone was significantly higher compared with IOP during the chemotherapy courses containing prednisolone. Only two patients complained of symptoms, such as headache and photophobia, and one of the two patients underwent trabeculotomy. Funduscopic findings were normal in all patients. There was a dose-associated decrease in IOP with reduction of dexamethasone dose. CONCLUSIONS: IOP should be measured during administration of substantial corticosteroid doses even in patients with no symptoms. Further investigations regarding the level of IOP for intervention need to be conducted.

DNA methylation-based classification reveals difference between pediatric T-cell acute lymphoblastic leukemia and normal thymocytes.
Shunsuke Kimura, Masafumi Seki, Tomoko Kawai, Hiroaki Goto, Kenichi Yoshida, Tomoya Isobe, Masahiro Sekiguchi, Kentaro Watanabe, Yasuo Kubota, Yasuhito Nannya, Hiroo Ueno, Yusuke Shiozawa, Hiromichi Suzuki, Yuichi Shiraishi, Kentaro Ohki, Motohiro Kato, Katsuyoshi Koh, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Atsushi Manabe, Masashi Sanada, Marc R Mansour, Akira Ohara, Keizo Horibe, Masao Kobayashi, Akira Oka, Yasuhide Hayashi, Satoru Miyano, Kenichiro Hata, Seishi Ogawa, Junko Takita
Leukemia, 34, 4, 1163, 1168, 2019年11月15日, ［査読有り］, ［国際誌］
英語

Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia.
Daisuke Hasegawa, Yuri Yoshimoto, Shunsuke Kimura, Tadashi Kumamoto, Naoko Maeda, Junichi Hara, Atsushi Kikuta, Akiko Kada, Toshimi Kimura, Yuka Iijima-Yamashita, Akiko M Saito, Keizo Horibe, Atsushi Manabe, Chitose Ogawa
International journal of hematology, 110, 5, 627, 634, 2019年11月, ［国内誌］
英語, 研究論文（学術雑誌）, Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study entry was 5, 7, and 7 years old, respectively. Two patients had hyperdiploid B-precursor ALL, and one had T cell ALL. Although all patients experienced grade 3-4 hematologic toxicity and grade 3 elevation of aminotransferases, no dose-limiting toxicities were observed. The maximum tolerated dose was defined as 1.3 mg/m2. Peripheral neuropathy and respiratory complications were not observed. Complete remission was achieved in all three patients. The mean maximum plasma concentration and area under the concentration-time curve was 74.0 ng/mL and 73.9 ng h/mL, respectively. Thus, adding BZM to 5-drug induction chemotherapy appears safe and well-tolerated in Japanese children with relapsed ALL.

Very late relapse cases of TCF3-ZNF384-positive acute lymphoblastic leukemia.
Akira Nishimura, Daisuke Hasegawa, Shinsuke Hirabayashi, Shoichiro Kanabuchi, Kaoru Yamamoto, Saori Aiga, Misa Nishitani, Yosuke Hosoya, Yasushi Noguchi, Kentaro Ohki, Nobutaka Kiyokawa, Shinichiro Mori, Atsushi Manabe
Pediatric blood & cancer, 66, 11, e27891, 2019年11月, ［査読有り］, ［国際誌］
英語

Nationwide survey of pediatric hypodiploid acute lymphoblastic leukemia in Japan.
Sae Ishimaru, Yasuhiro Okamoto, Chihaya Imai, Hirotoshi Sakaguchi, Tomohiko Taki, Daisuke Hasegawa, Yuko Cho, Harumi Kakuda, Hideki Sano, Atsushi Manabe, Toshihiko Imamura, Motohiro Kato, Yuki Arakawa, Hidemi Shimonodan, Atsushi Sato, Souichi Suenobu, Takeshi Inukai, Arata Watanabe, Yoshifumi Kawano, Atsushi Kikuta, Keizo Horibe, Akira Ohara, Katsuyoshi Koh
Pediatrics international : official journal of the Japan Pediatric Society, 61, 11, 1103, 1108, 2019年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children. METHODS: We retrospectively collected clinical data on hypodiploid ALL cases from the registries of prospective multicenter trials conducted by the four independent clinical study groups in Japan between 1997 and 2012. RESULTS: A total of 117 ALL patients with hypodiploidy were analyzed in this study. There were 101, eight, and eight patients with 45, 44, and fewer than 44 chromosomes, respectively. The 5 year overall survival rates differed significantly: 86.0%, 87.5%, and 62.5% for patients with 45, 44, and fewer than 44 chromosomes, respectively (P = 0.037). Of the eight patients with 44 chromosomes, seven were alive, including five patients who maintained complete remission without undergoing hematopoietic stem cell transplantation (HSCT). Of the eight patients with fewer than 44 chromosomes, six were good responders to prednisolone and none had induction failure, but the relapse rate was high (5/8). No patients had central nervous system relapse. Four patients underwent HSCT after relapse, but only one survived. CONCLUSIONS: Outcomes of Japanese ALL patients with fewer than 44 chromosomes were poor, as previously reported in other countries. Although the sample size was small, patients with 44 chromosomes had better prognoses than those previously reported. Further studies including international collaboration are needed to improve outcomes for pediatric ALL patients with fewer than 44 chromosomes.

【2019年の白血病診療-新たな武器を上手に活用するために】フィラデルフィア染色体様(Ph-like)急性リンパ性白血病の診断と治療
小野 林太郎, 真部 淳
内科, 124, 4, 2167, 2169, (株)南江堂, 2019年10月
日本語, ＜文献概要＞▼遺伝子解析技術の進歩により,Ph+ALLと類似した遺伝子発現パターンを呈するB前駆細胞型ALLの一群が同定された.▼Ph-like ALLではIKZF1の遺伝子異常に加え,ABL1関連遺伝子やJAK関連遺伝子異常など,キナーゼ遺伝子の変異を高率に伴うことが示されている.▼Ph-like ALLは男児に多く,初診時白血球数が多く,また寛解導入療法後のMRD陽性例を多く認める.▼当初は予後不良と考えられていたが,MRDによる治療層別化により,その他のB前駆細胞型ALLと同等の成績が得られている.▼チロシンキナーゼ阻害薬やJAK阻害薬による治療効果が期待され,今後前向き臨床試験での検証が望まれる.

Germline GATA2変異を伴う骨髄異形成症候群(MDS)の1例　　　　　　　　　　　　　　　
水城 和義, 平林 真介, 長谷川 大輔, 山本 俊亮, 山本 薫, 足洗 美穂, 小野 林太郎, 細谷 要介, 鈴木 美慧, 松本 公宏, 川口 裕之, 真部 淳
臨床血液, 60, 10, 1502, 1502, (一社)日本血液学会-東京事務局, 2019年10月
日本語

長期にわたる免疫抑制治療後にステロイド離脱が可能となった移植後自己免疫性溶血性貧血(AIHA)　　　　　　　　　　　　　　　
小野 林太郎, 細谷 要介, 山本 俊亮, 山本 薫, 西村 聡, 足洗 美穂, 平林 真介, 長谷川 大輔, 真部 淳
日本小児血液・がん学会雑誌, 56, 4, 324, 324, (一社)日本小児血液・がん学会, 2019年10月
日本語

ウィリアムズ症候群を背景に発症したバーキットリンパ腫　　　　　　　　　　　　　　　
長谷河 昌孝, 長 祐子, 原 和也, 寺下 友佳代, 杉山 未奈子, 大久保 淳, 井口 晶裕, 真部 淳, 荒 桃子, 本多 昌平, 武冨 紹信, 高桑 恵美, 松野 吉宏
日本小児血液・がん学会雑誌, 56, 4, 299, 299, (一社)日本小児血液・がん学会, 2019年10月, ［査読有り］
日本語

Pediatric patients with cancer predisposition in Japan: Results of a questionnaire survey.
Yoshiko Nakano, Yukiko Tsunematsu, Fumito Yamazaki, Atsushi Manabe, Akira Nakagawara, Eiso Hiyama, Tadashi Kumamoto
Pediatric blood & cancer, 66, 10, e27937, 2019年10月, ［査読有り］, ［国際誌］
英語

過去10年間に当院外来を受診した異物誤飲の小児患者に関する検討　　　　　　　　　　　　　　　
山本 俊亮, 島袋 林秀, 梅原 直, 右田 美里, 平田 倫生, 小澤 美和, 真部 淳, 松藤 凡, 草川 功
日本小児救急医学会雑誌, 18, 3, 343, 347, (一社)日本小児救急医学会, 2019年10月, ［査読有り］
日本語, 2007年〜2016年の10年間で、当院を受診した異物誤飲に関連した小児患者(誤飲関連受診患者)534名を後方視的に調査した。発生状況や画像検査により異物誤飲が確認された患者(誤飲診断患者)は324名で、そのうち4歳以下の乳幼児が80%以上を占めていた。受診時間帯は16〜24時が多く、誤飲関連受診患者数および誤飲診断患者数ともに増加傾向にあった。誤飲診断患者の割合は約60%で10年間ほぼ一定の割合であった。また、画像検査の施行件数も増加する一方、画像検査で診断できた症例(画像診断患者)は30-40%で経年的変化はなかった。誤飲したかもしれないという受診者の不安・心配を許容しつつも、緊急性の高い対象物を具体的に把握して不要な画像検索を避けること、緊急性が高い対象物については重点的に予防の必要性について啓発活動を行うことが今後の課題であった。(著者抄録)

Break Apart FISH Probeで転座判定に苦慮したKMT2A-MLLT10 mRNA陽性AMLの一症例
小栗 聡, 佐藤 かおり, 市川 絢子, 藤澤 真一, 原 和也, 杉山 未奈子, 寺下 友佳代, 長 祐子, 井口 晶裕, 杉田 純一, 西田 睦, 豊嶋 崇徳, 真部 淳
日本染色体遺伝子検査学会雑誌, 37, 2, 47, 47, 日本染色体遺伝子検査学会, 2019年09月
日本語

Efficacy of the NCCV Cocktail‐1 vaccine for refractory pediatric solid tumors: a phase I clinical trial
Akazawa Y, Hosono A, Yoshikawa T, Kaneda H, Nitani C, Hara J, Kinoshita Y, Kohashi K, Manabe A, Fukutani M, Wakabayashi M, Sato A, Shoda K, Shimomura M, Mizuno S, Nakamoto Y, Nakatsura T
Cancer Science, 110, 12, 3650, 3662, Wiley, 2019年09月, ［査読有り］
研究論文（学術雑誌）

A germline HLTF mutation in familial MDS induces DNA damage accumulation through impaired PCNA polyubiquitination.
Kensuke Takaoka, Masahito Kawazu, Junji Koya, Akihide Yoshimi, Yosuke Masamoto, Hiroaki Maki, Takashi Toya, Takashi Kobayashi, Yasuhito Nannya, Shunya Arai, Toshihide Ueno, Hironori Ueno, Kenshi Suzuki, Hironori Harada, Atsushi Manabe, Yasuhide Hayashi, Hiroyuki Mano, Mineo Kurokawa
Leukemia, 33, 7, 1773, 1782, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Although several causal genes of familial myelodysplastic syndromes (MDS) have been identified, the genetic landscape and the molecular pathogenesis are not totally understood. To explore novel driver genes and their pathogenetic significance, we performed whole-exome sequence analysis of four individuals from a familial MDS pedigree and 10 candidate single-nucleotide variants (C9orf43, CYP7B1, EFHB, ENTPD7, FAM160B2, HELZ2, HLTF, INPP5J, ITPKB, and RYK) were identified. Knockdown screening revealed that Hltf downregulation enhanced colony-forming capacity of primary murine bone marrow (BM) stem/progenitor cells. γH2AX immunofluorescent staining assay revealed increased DNA damage in a human acute myeloid leukemia (AML) cell line ectopically expressing HLTF E259K, which was not observed in cells expressing wild-type HLTF. Silencing of HLTF in human AML cells also led to DNA damage, indicating that HLTF E259K is a loss-of-function mutation. Molecularly, we found that an E259K mutation reduced the binding capacity of HLTF with ubiquitin-conjugating enzymes, methanesulfonate sensitive 2 and ubiquitin-conjugating enzyme E2N, resulting in impaired polyubiquitination of proliferating cell nuclear antigen (PCNA) in HLTF E259K-transduced cells. In summary, our results indicate that a familial MDS-associated HLTF E259K germline mutation induces accumulation of DNA double-strand breaks, possibly through impaired PCNA polyubiquitination.

Kawasaki disease shock syndrome: Case report and cytokine profiling.
Ono R, Shimizu M, Yamamoto K, Umehara N, Manabe A
Pediatrics international : official journal of the Japan Pediatric Society, 61, 6, 620, 622, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Dasatinib and low-intensity chemotherapy for Philadelphia chromosome–positive acute lymphoblastic leukemia in a child with Down syndrome
Hirabayashi S, Hasegawa D, Yamamoto K, Nishimura A, Hosoya Y, Shuo T, Kiyokawa N, Miura M, Takahashi N, Manabe A
Pediatric Blood & Cancer, 66, 5, e27612, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Clinical and biological features of paediatric acute myeloid leukaemia (AML) with primary induction failure in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.
Miyamura T, Moritake H, Nakayama H, Tanaka S, Tomizawa D, Shiba N, Saito AM, Tawa A, Shimada A, Iwamoto S, Hayashi Y, Koike T, Horibe K, Manabe A, Mizutani S, Taga T, Adachi S
British journal of haematology, 185, 2, 284, 288, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The prognosis of paediatric acute myeloid leukaemia (AML) with primary induction failure (PIF) is extremely poor, and effective treatment strategies have not been established. We investigated the clinical and biological features of paediatric AML patients with PIF registered to the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study. The 3-year overall survival rate of the 41 PIF patients was 19.0%. High leucocyte count, M7 morphology, and unfavourable genetic aberrations, such as FLT3-internal tandem duplication, NUP98-NSD1 and high MECOM or PRDM16 expression, were risk factors for PIF. More effective treatment strategies based on leukaemia biology need to be urgently explored.

画像診断 今月の症例 心膜外脂肪壊死(epipericardial fat necrosis:EFN)
佐藤 崇翔, 野崎 太希, 松迫 正樹, 真部 淳, 宮嵜 治
小児科臨床, 72, 3, 233, 236, (株)日本小児医事出版社, 2019年03月
日本語

小児急性リンパ性白血病における高用量メトトレキサート投与時の薬物動態解析　　　　　　　　　　　　　　　
田中 庸一, 浦山 ケビン, 森 麻希子, 長谷川 大輔, 赤羽 弘資, 太田 節雄, 真部 淳
日本薬学会年会要旨集, 139年会, 4, 65, 65, (公社)日本薬学会, 2019年03月, ［査読有り］
日本語

川崎病急性期に急性腎不全、顕性黄疸、低酸素血症、低血圧を合併した10歳女児の1例
小野 林太郎, 山本 俊亮, 山本 薫, 梅原 直, 清水 正樹, 谷内江 昭宏, 真部 淳
心臓, 51, 3, 365, 366, (公財)日本心臓財団, 2019年03月
日本語, 研究論文（学術雑誌）

Duplication of ALK F1245 missense mutation due to acquired uniparental disomy associated with aggressive progression in a patient with relapsed neuroblastoma.
Shunsuke Kimura, Daisuke Hasegawa, Yuri Yoshimoto, Masafumi Seki, Atsuro Daida, Masahiro Sekiguchi, Shinsuke Hirabayashi, Yosuke Hosoya, Masao Kobayashi, Satoru Miyano, Seishi Ogawa, Junko Takita, Atsushi Manabe
Oncology letters, 17, 3, 3323, 3329, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Recent genome-wide analysis of neuroblastoma (NBL) revealed amplification and heterozygous mutation of anaplastic lymphoma kinase (ALK) are responsible for oncogenicity, frequently observed during relapses. A 3-year-old girl with relapsed high-risk NBL had a heterozygous ALK F1245L mutation at diagnosis, which became homozygous due to uniparental disomy (UPD) of the entire chromosome 2, confirmed by single nucleotide polymorphism array and variant allele frequency of this mutation. The ALK inhibitor, crizotinib, failed to control the tumor and the patient died of the disease. Further genomic analysis using targeted capture sequencing for 381 genes related to pediatric cancers identified more alterations acquired at relapse, such as TSC complex subunit 2 and protein tyrosine phosphatase receptor type D. In addition to these several acquired mutations, this extremely rare duplication of ALK mutation might explain the aggressive clinical course after relapse, because acquired UPD, resulting in the duplication of an oncogenic mutation, has been reported for various neoplasms. Although a clinical benefit of ALK inhibitors in patients with NBL has not been confirmed yet, a treatment based on the ALK mutation status will be promising in future using more potent next-generation ALK inhibitors.

腸管気腫を来した血液腫瘍性疾患・原発性免疫不全症の5例　　　　　　　　　　　　　　　
西村 聡, 足洗 美穂, 神谷 尚宏, 山本 俊亮, 山本 薫, 友田 昂宏, 井上 真依子, 井上 健斗, 宮本 智史, 小野 林太郎, 平林 真介, 磯田 健志, 柳町 昌克, 細谷 要介, 長谷川 大輔, 今井 耕輔, 高木 正稔, 金兼 弘和, 真部 淳, 森尾 友宏
日本小児科学会雑誌, 123, 2, 273, 273, (公社)日本小児科学会, 2019年02月
日本語

寛解導入療法中に肺胞出血をきたしNO吸入療法が有効であったAMLの1例　　　　　　　　　　　　　　　
足洗 美穂, 梅原 直, 黒子 由梨香, 山本 薫, 山本 俊亮, 小野 林太郎, 平林 真介, 細谷 要介, 長谷川 大輔, 真部 淳
日本小児科学会雑誌, 123, 2, 320, 320, (公社)日本小児科学会, 2019年02月
日本語

Pediatric oncologic emergencies: Clinical and imaging review for pediatricians.
Atsuhiko Handa, Taiki Nozaki, Akari Makidono, Tetsuhiko Okabe, Yuka Morita, Kazutoshi Fujita, Masaki Matsusako, Tatsuo Kono, Yasuyuki Kurihara, Daisuke Hasegawa, Tadashi Kumamoto, Chitose Ogawa, Yuki Yuza, Atsushi Manabe
Pediatrics international : official journal of the Japan Pediatric Society, 61, 2, 122, 139, 2019年02月, ［国際誌］
英語, 研究論文（学術雑誌）, Children with cancer are at increased risk of life-threatening emergencies, either from the cancer itself or related to the cancer treatment. These conditions need to be assessed and treated as early as possible to minimize morbidity and mortality. Cardiothoracic emergencies encompass a variety of pathologies, including pericardial effusion and cardiac tamponade, massive hemoptysis, superior vena cava syndrome, pulmonary embolism, and pneumonia. Abdominal emergencies include bowel obstruction, intussusception, perforation, tumor rupture, intestinal graft-versus-host disease, acute pancreatitis, neutropenic colitis, and obstructive uropathy. Radiology plays a vital role in the diagnosis of these emergencies. We here review the clinical features and imaging in pediatric patients with oncologic emergencies, including a review of recently published studies. Key radiological images are presented to highlight the radiological approach to diagnosis. Pediatricians, pediatric surgeons, and pediatric radiologists need to work together to arrive at the correct diagnosis and to ensure prompt and appropriate treatment strategies.

NOTCH1 pathway activating mutations and clonal evolution in pediatric T-cell acute lymphoblastic leukemia.
Kimura S, Seki M, Yoshida K, Shiraishi Y, Akiyama M, Koh K, Imamura T, Manabe A, Hayashi Y, Kobayashi M, Oka A, Miyano S, Ogawa S, Takita J
Cancer science, 110, 2, 784, 794, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Molecular mechanisms involved in the relapse of T-cell acute lymphoblastic leukemia (T-ALL) are not fully understood, although activating NOTCH1 signaling due to NOTCH1/FBXW7 alterations is a major oncogenic driver. To unravel the relevance of NOTCH1/FBXW7 mutations associated with relapse, we performed whole-exome sequencing in 30 pediatric T-ALL cases, among which 11 diagnosis-relapse paired cases were further investigated to track the clonal evolution of relapse using amplicon-based deep sequencing. NOTCH1/FBXW7 alterations were detected in 73.3% (diagnosis) and 72.7% (relapse) of cases. Single nucleotide variations in the heterodimerization domain were the most frequent (40.0%) at diagnosis, whereas proline, glutamic acid, serine, threonine-rich (PEST) domain alterations were the most frequent at relapse (54.5%). Comparison between non-relapsed and relapsed cases at diagnosis showed a predominance of PEST alterations in relapsed cases (P = .045), although we failed to validate this in the TARGET cohort. Based on the clonal analysis of diagnosis-relapse samples, we identified NOTCH1 "switching" characterized by different NOTCH1 mutations in a major clone between diagnosis and relapse samples in 2 out of 11 diagnosis-relapse paired cases analyzed. We found another NOTCH1 "switching" case in a previously reported Berlin-Frankfurt-Münster cohort (n = 13), indicating NOTCH1 importance in both the development and progression of T-ALL. Despite the limitations of having a small sample size and a non-minimal residual disease-based protocol, our results suggest that the presence of NOTCH1 mutations might contribute to the disease relapse of T-ALL.

Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion.
Kentaro Ohki, Nobutaka Kiyokawa, Yuya Saito, Shinsuke Hirabayashi, Kazuhiko Nakabayashi, Hitoshi Ichikawa, Yukihide Momozawa, Kohji Okamura, Ai Yoshimi, Hiroko Ogata-Kawata, Hiromi Sakamoto, Motohiro Kato, Keitaro Fukushima, Daisuke Hasegawa, Hiroko Fukushima, Masako Imai, Ryosuke Kajiwara, Takashi Koike, Isao Komori, Atsushi Matsui, Makiko Mori, Koichi Moriwaki, Yasushi Noguchi, Myoung-Ja Park, Takahiro Ueda, Shohei Yamamoto, Koichi Matsuda, Teruhiko Yoshida, Kenji Matsumoto, Kenichiro Hata, Michiaki Kubo, Yoichi Matsubara, Hiroyuki Takahashi, Takashi Fukushima, Yasuhide Hayashi, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara
Haematologica, 104, 1, 128, 137, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We identified 16 cases of acute lymphoblastic leukemia and 1 of lymphoma harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive precursor B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic μ chain-positive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of HDAC9 and MEF2C, elevated GATA3 expression was also a characteristic feature of MEF2D fusion-positive patients. Mutations of PHF6, recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. MEF2D fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/ml) at presentation and, as a result, were mostly classified as NCI high risk. Although they responded well to steroid treatment, MEF2D fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as salvage therapy. Interestingly, relapse was frequently associated with the presence of CDKN2A/CDKN2B gene deletions. Our observations indicate that MEF2D fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.

Diplotype analysis of NUDT15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms.
Shinichi Tsujimoto, Tomoo Osumi, Meri Uchiyama, Ryota Shirai, Takaya Moriyama, Rina Nishii, Yuji Yamada, Ko Kudo, Masahiro Sekiguchi, Yuki Arakawa, Masanori Yoshida, Toru Uchiyama, Kiminori Terui, Shuichi Ito, Katsuyoshi Koh, Junko Takita, Etsuro Ito, Daisuke Tomizawa, Atsushi Manabe, Nobutaka Kiyokawa, Jun J Yang, Motohiro Kato
Leukemia, 32, 12, 2710, 2714, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group.
Hidemitsu Kurosawa, Akihiko Tanizawa, Hideki Muramatsu, Chikako Tono, Akihiro Watanabe, Haruko Shima, Masaki Ito, Yuki Yuza, Kazuko Hamamoto, Noriko Hotta, Masahiko Okada, Akiko Moriya Saito, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Keizo Horibe, Eiichi Ishii, Hiroyuki Shimada
Pediatric blood & cancer, 65, 12, e27368, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The details of the sequential use of imatinib for first-line treatment followed by second-generation tyrosine kinase inhibitors (2G-TKIs) for pediatric chronic myeloid leukemia (CML) are still unknown. This study analyzed clinical responses and adverse effects of the use of 2G-TKIs following imatinib in pediatric chronic phase (CP)-CML. PROCEDURES: The Japanese Pediatric Leukemia/Lymphoma Study Group conducted a retrospective study of patients with newly diagnosed CML from 1996 to 2011. A total of 152 cases that received imatinib as first-line therapy were analyzed. RESULTS: Excluding 46 cases treated with hematopoietic stem cell transplantation before nilotinib and dasatinib became available, 31 of 106 patients changed to 2G-TKIs. The primary reason for changing from imatinib was poor response, followed by intolerance, with the main reason for the latter being musculoskeletal events. Switches from imatinib to 2G-TKIs with intolerance occurred significantly earlier than switches with poor response. Sixteen and 15 patients were treated with nilotinib and dasatinib, respectively, following imatinib therapy. After switching to 2G-TKIs, the response status improved in 63% of evaluable patients. The adverse effect profiles of nilotinib and dasatinib tended to be different, with hyperbilirubinemia observed in 33% of nilotinib-treated patients, but in none of the cases with dasatinib. CONCLUSION: This retrospective study represents the first series of children and adolescents in whom sequential use of imatinib followed by 2G-TKIs was reported. These data provide useful insights into the selection of 2G-TKIs as first-line treatment for children and adolescents with CP-CML.

Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese
Kevin Y. Urayama, Masatoshi Takagi, Takahisa Kawaguchi, Keitaro Matsuo, Yoichi Tanaka, Yoko Ayukawa, Yuki Arakawa, Daisuke Hasegawa, Yuki Yuza, Takashi Kaneko, Yasushi Noguchi, Yuichi Taneyama, Setsuo Ota, Takeshi Inukai, Masakatsu Yanagimachi, Dai Keino, Kazutoshi Koike, Daisuke Toyama, Yozo Nakazawa, Hidemitsu Kurosawa, Kozue Nakamura, Koichi Moriwaki, Hiroaki Goto, Yujin Sekinaka, Daisuke Morita, Motohiro Kato, Junko Takita, Toshihiro Tanaka, Johji Inazawa, Katsuyoshi Koh, Yasushi Ishida, Akira Ohara, Shuki Mizutani, Fumihiko Matsuda, Atsushi Manabe
Scientific Reports, 8, 1, 789, Nature Publishing Group, 2018年12月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Genome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years) previously enrolled onto a Tokyo Children's Cancer Study Group trial were collected during 2013-2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis. Cases and control data for 3,882 samples from the Nagahama Study Group and Aichi Cancer Center Study were combined, and association analyses across 10 previous GWAS-identified regions were performed after targeted SNP imputation. Linkage disequilibrium (LD) patterns in Japanese and other populations were evaluated using the varLD score based on 1000 Genomes data. Risk associations for ARID5B (rs10821936, OR = 1.84, P = 6 × 10-17) and PIP4K2A (rs7088318, OR = 0.76, P = 2 × 10-4) directly transferred to Japanese, and the IKZF1 association was detected by an alternate SNP (rs1451367, OR = 1.52, P = 2 × 10-6). Marked regional LD differences between Japanese and Europeans was observed for most of the remaining loci for which associations did not transfer, including CEBPE, CDKN2A, CDKN2B, and ELK3. This study represents a first step towards characterizing the role of genetic susceptibility in childhood ALL risk in Japanese.

Clinical and Genetic Characteristics of Patients with Shwachman-Diamond Syndrome in Japan
Watanabe Kenichiro, Kanegane Hirokazu, Hamabata Takayuki, Kozuki Kagehiro, Umeda Katsutsugu, Ueno Hiroo, Yoshida Kenichi, Hama Asahito, Okuno Yusuke, Muramatsu Hideki, Takahashi Yoshiyuki, Hasegawa Daisuke, Manabe Atsushi, Ohara Akira, Ito Masafumi, Ogawa Seishi, Kojima Seiji, Ito Etsuro
BLOOD, 132, 2018年11月29日
英語, 研究論文（学術雑誌）

Diagnosis of Inherited Bone Marrow Failure Syndromes Using Sequencing Approaches　　　　　　　　　　　　　　　
Narita Atsushi, Muramatsu Hideki, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Sakaguchi Hirotoshi, Kawashima Nozomu, Wang Xinan, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Hama Asahito, Sanada Masashi, Hitoshi Kanno, Yamaguchi Hiroki, Ohga Shouichi, Manabe Atsushi, Harigae Hideo, Kunishima Shinji, Ishii Eiichi, Kobayashi Masao, Koike Kenichi, Watanabe Kenichiro, Ito Etsuro, Takata Minoru, Yabe Miharu, Ogawa Seishi, Miyano Satoru, Kojima Seiji, Takahashi Yoshiyuki
PEDIATRIC BLOOD & CANCER, 65, S7-S7, 2018年11月
英語, 研究論文（学術雑誌）

Treatment Outcome of Children with Acute Lymphoblastic Leukemia Harbouring Newly Identified Genetic Abnormalities: Results from TCCSG Study L04-16
Ohki Kentaro, Kiyokawa Nobutaka, Takahashi Hiroyuki, Kajiwara Ryosuke, Kato Motohiro, Hasegawa Daisuke, Tomizawa Daisuke, Noguchi Yasushi, Koike Kazutoshi, Toyama Daisuke, Yabe Hiromasa, Michiko Kajiwara, Fujimura Junya, Sotomatsu Manabu, Ota Setsuo, Maeda Miho, Goto Hiroaki, Kato Yoko, Mori Tetsuya, Inukai Takeshi, Shimada Hiroyuki, Fukushima Keitaro, Ogawa Chitose, Fukushima Takashi, Koh Katsuyoshi, Manabe Atsushi, Ohara Akira
PEDIATRIC BLOOD & CANCER, 65, S7, S8, WILEY, 2018年11月, ［査読有り］
英語

Morphological Features of Bone Marrow in Patients with Inherited Bone Marrow Failure　　　　　　　　　　　　　　　
Hama Asahito, Hasegawa Daisuke, Manabe Atsushi, Nozawa Kazue, Narita Atsushi, Okuno Yusuke, Muramatsu Hideki, Takahashi Yoshiyuki, Watanabe Kenichiro, Ohara Akira, Ito Masafumi, Kojima Seiji
PEDIATRIC BLOOD & CANCER, 65, S66-S66, 2018年11月
英語, 研究論文（学術雑誌）

Clinical characteristics of pediatric patients with myeloid sarcoma without bone marrow involvement in Japan.
Taga T, Imamura T, Nakashima K, Maeda N, Watanabe A, Miyajima Y, Sakaguchi S, Sano H, Hasegawa D, Kawasaki H, Adachi S, Takagi M, Koh K, Manabe A, Taki T, Ishida Y
International journal of hematology, 108, 4, 438, 442, 2018年10月, ［査読有り］
研究論文（学術雑誌）, Myeloid sarcoma (MS) is a rare neoplastic condition that is often described in association with acute myeloid leukemia (AML). MS in childhood has received little attention, particularly in Japan. We carried out a nationwide retrospective analysis of Japanese children diagnosed with MS without bone marrow involvement. Inclusion criteria were diagnosis of MS at younger than 20 years of age between January 1, 2000 and December 31, 2013. There was a predominance of males (8:2), and the median age at MS diagnosis was 4 years. Sites of involvement varied and included skin (n = 3), head and/or neck (n = 2), and multiple sites (n = 2). Karyotypes were evaluated in seven patients, with one individual carrying t(8;21) and t(9;11). Four patients developed bone marrow involvement 2–55 months after diagnosis of MS. All patients received chemotherapy for de novo AML and two individuals received HSCT in first remission. Seven of ten patients survived for 50–152 months (median, 93 months) without disease after initial chemotherapy. This retrospective study confirmed that pediatric MS without bone marrow involvement in Japan is a very rare disease. MS patients responded favorably to therapies for de novo AML, and HSCT in first remission was not indicated for all patients.

シーケンスによる先天性骨髄不全症の診断(Diagnosis of Inherited Bone Marrow Failure Syndromes Using Sequencing Approaches)
Narita Atsushi, Muramatsu Hideki, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Sakaguchi Hirotoshi, Kawashima Nozomu, Wang Xinan, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Hama Asahito, Sanada Masashi, Kanno Hitoshi, Yamaguchi Hiroki, Ohga Shouichi, Manabe Atsushi, Harigae Hideo, Kunishima Shinji, Ishii Eiichi, Kobayashi Masao, Koike Kenichi, Watanabe Kenichiro, Ito Etsuro, Takata Minoru, Yabe Miharu, Ogawa Seishi, Miyano Satoru, Kojima Seiji, Takahashi Yoshiyuki
日本小児血液・がん学会雑誌, 55, 4, 153, 153, (一社)日本小児血液・がん学会, 2018年10月
英語

腸管気腫を来した血液腫瘍性疾患の2例
山本 俊亮, 西村 聡, 小野 林太郎, 山本 薫, 足洗 美穂, 平林 真介, 細谷 要介, 長谷川 大輔, 真部 淳
日本小児血液・がん学会雑誌, 55, 4, 335, 335, (一社)日本小児血液・がん学会, 2018年10月
日本語

AYA世代の小児がん経験者とそのきょうだいの心的外傷後ストレス症状(PTSS)と外傷体験後成長(PTG)
山本 薫, 永瀬 恭子, 郡司 美千代, 小林 京子, 平林 真介, 細谷 要介, 長谷川 大輔, 細谷 亮太, 石田 也寸志, 真部 淳, 小澤 美和
日本小児血液・がん学会雑誌, 55, 4, 343, 343, (一社)日本小児血液・がん学会, 2018年10月
日本語

小児がん経験者の知識とセルフマネジメントスキルの現状
小林 京子, 石田 也寸志, 郡司 美千代, 永瀬 恭子, 前田 邦枝, 小澤 美和, 細谷 要介, 長谷川 大輔, 細谷 亮太, 真部 淳
日本小児血液・がん学会雑誌, 55, 4, 382, 382, (一社)日本小児血液・がん学会, 2018年10月
日本語

集中治療室入院中の患児のきょうだいへの支援の一例
大久保 香織, 三浦 絵莉子, 野口 楓, 植松 温子, 長谷川 大輔, 小澤 美和, 真部 淳
日本小児血液・がん学会雑誌, 55, 4, 391, 391, (一社)日本小児血液・がん学会, 2018年10月
日本語

Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia.
Motoharu Hamada, Sayoko Doisaki, Yusuke Okuno, Hideki Muramatsu, Asahito Hama, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Kenichi Yoshida, Hitoshi Kanno, Atsushi Manabe, Takashi Taga, Yoshiyuki Takahashi, Satoru Miyano, Seishi Ogawa, Seiji Kojima
International journal of hematology, 108, 3, 306, 311, 2018年09月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.

Secondary bone/soft tissue sarcoma in childhood cancer survivors: a nationwide hospital-based case-series study in Japan.
Ishida Y, Maeda M, Adachi S, Rikiishi T, Sato M, Kawaguchi H, Manabe A, Tokuyama M, Hori H, Okamura J, Ogawa A, Goto H, Kobayashi R, Yoshinaga S, Fujimoto J, Kuroda T
Japanese journal of clinical oncology, 48, 9, 806, 814, 2018年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Secondary cancer is the most life-threatening late effect of childhood cancer. We investigated the clinical features of secondary bone/soft tissue sarcoma among childhood cancer survivors (CCSs). Methods: We conducted a retrospective case-series study of 10 069 CCSs newly diagnosed with cancer between 1980 and 2009 across 15 Japanese hospitals. Twenty-one cases of pathologically diagnosed secondary bone/soft tissue sarcoma were selected, and the respective clinical courses were determined using additional questionnaires. Results: The primary cancers included retinoblastoma (n = 7), acute lymphoblastic leukemia (n = 5), lymphoma (n = 5), osteosarcoma (n = 1), rhabdomyosarcoma (n = 1), brain tumor (n = 1) and Langerhans cell histiocytosis (n = 1). The median age at the primary cancer diagnosis was 2.9 years, and the male-to-female ratio was 16:5. The histological classifications of the secondary sarcoma included osteosarcoma (n = 10), malignant peripheral nerve sheath tumor (n = 4), rhabdomyosarcoma (n = 3), Ewing's sarcoma (n = 3) and primitive neuroectodermal tumor (n = 1). The median latency period to the secondary sarcoma was 10.2 years. Significant risk factors for secondary sarcoma in the multivariate Cox regression model included a history of retinoblastoma as the primary cancer (hazard ratio [HR], 20.9; 95% confidence interval [CI], 5.70-76.5) and autologous stem cell transplantation (SCT) (HR, 2.56; 95% CI, 1.08-6.03). Seventeen CCSs with secondary sarcoma underwent radiation, and nine, hematopoietic SCT. Twelve CCSs with secondary sarcoma achieved disease-free survival, while CCSs with hematological cancer or relapsed primary cancer who developed secondary sarcoma had the worst prognoses. Conclusion: The prognoses of CCSs with secondary sarcoma may depend on the primary cancer or prior relapse of primary cancer.

本邦におけるShwachman-Diamond症候群の全国的コホートの構築(Establishment of a nationwide cohort for Shwachman-Diamond syndrome in Japan)　　　　　　　　　　　　　　　
渡邉 健一郎, 金兼 弘和, 濱端 隆行, 上月 景弘, 梅田 雄嗣, 濱 麻人, 奥野 友介, 村松 秀城, 高橋 義行, 長谷川 大輔, 真部 淳, 小原 明, 伊藤 雅文, 小島 勢二, 伊藤 悦朗
臨床血液, 59, 9, 1497, 1497, (一社)日本血液学会-東京事務局, 2018年09月, ［査読有り］
英語

Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16
Hiroyuki Takahashi, Ryosuke Kajiwara, Motohiro Kato, Daisuke Hasegawa, Daisuke Tomizawa, Yasushi Noguchi, Kazutoshi Koike, Daisuke Toyama, Hiromasa Yabe, Michiko Kajiwara, Junya Fujimura, Manabu Sotomatsu, Setsuo Ota, Miho Maeda, Hiroaki Goto, Yoko Kato, Tetsuya Mori, Takeshi Inukai, Hiroyuki Shimada, Keitaro Fukushima, Chitose Ogawa, Atsushi Makimoto, Takashi Fukushima, Kentaro Ohki, Katsuyoshi Koh, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara
International Journal of Hematology, 108, 1, 98, 108, Springer Tokyo, 2018年07月01日, ［査読有り］
英語, 研究論文（学術雑誌）, The survival rate of children with acute lymphoblastic leukemia (ALL) has increased to approximately 90% after substantial progress in risk-oriented treatment strategies. Between 2005 and 2013, the Tokyo Children’s Cancer Study Group (TCCSG) conducted a risk-oriented, non-randomized study, L04-16. The principal aim of this study was to assemble background characteristics and treatment outcomes, and gather genetic information on leukemic cells under central diagnosis. This report outlines the background characteristics and treatment outcomes of 1033 children with ALL treated according to a TCCSG platform. The 5-year event-free and overall survival (OS) rates for all children were 78.1 ± 1.3 and 89.6 ± 1.0%, respectively. The OS rate was significantly higher in children with B-cell precursor (BCP)-ALL (91.9 ± 1.0%, n = 916) than in those with T-ALL (71.9 ± 4.3%, n = 117, p &
lt
0.001). In univariate analysis for BCP-ALL, children aged 1–6 years (5y-OS: 94.2 ± 1.0%), with an initial white blood cell count of &
lt
20,000/μL (94.0 ± 1.0%), high hyperdiploidy (95.4 ± 1.6%), ETV6-RUNX1 (97.4 ± 1.2%) or TCF3-PBX1 (96.9 ± 2.1%), and “Day8NoBlasts” (96.4 ± 1.1%) had the best outcomes. Genetic investigation revealed two novel fusion genes within this cohort: ETV6-ZNF385A and ZNF362-TCF4. Our study highlighted the clinical aspects of genomic features of ALL in Japanese children. We provide fundamental information for the further molecular investigation of this disease.

Phase II/III study in children and adolescents with newly diagnosed B-cell precursor acute lymphoblastic leukemia: protocol for a nationwide multicenter trial in Japan.
Koh K, Kato M, Saito AM, Kada A, Kawasaki H, Okamoto Y, Imamura T, Horibe K, Manabe A
Japanese journal of clinical oncology, 48, 7, 684, 691, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, B-cell precursor acute lymphoblastic leukemia is the most common pediatric malignancy, but its treatment needs to be modified to cause low acute toxicity and few late complications with a high cure rate. In this trial, we will stratify patients with B-cell precursor acute lymphoblastic leukemia into standard, intermediate and high risk groups according to prognostic factors. In addition, we will establish an evaluation system for minimal residual disease that will enable us to stratify patients based on minimal residual disease in subsequent clinical trials. We will clarify the impact of dexamethasone/vincristine pulse therapy during maintenance therapy in the standard risk group, and intensive l-asparaginase therapy in the intermediate risk group. In the high risk group, usefulness of vincristine intensification will be assessed. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000009339 [http://www.umin.ac.jp/ctr/].

Nationwide survey of therapy-related leukemia in childhood in Japan
Toshihiko Imamura, Takashi Taga, Masatoshi Takagi, Hirohide Kawasaki, Katsuyoshi Koh, Tomohiko Taki, Souichi Adachi, Atsushi Manabe, Yasushi Ishida, On behalf of the Leukemia/Lymphoma Committee
International Journal of Hematology, 108, 1, 91, 97, Springer Tokyo, 2018年07月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Therapy-related leukemia (t-leukemia) is associated with dismal prognosis. Published pediatric t-leukemia data are somewhat outdated and may not reflect recent advances in treatment. We report a retrospective nationwide survey of patients diagnosed between 2000 and 2013 in Japan. We identified 43 patients with pediatric t-leukemia
33 had t-acute myeloid leukemia (t-AML), eight had t-acute lymphoblastic leukemia (t-ALL) and two had t-acute undifferentiated leukemia. Median age at onset and latency were 12 years and 3.8 years, respectively, consistent with previous reports. Of t-AML patients, 63.6% harbored topoisomerase II inhibitor (topo II)-related genetic abnormalities, while only 12.5% of t-ALL patients had such alterations, suggesting that topo II is not key to t-ALL leukemogenesis. The 7-year overall survival (OS) for all 43 patients was 39.2 ± 11.6%. The 5-year OS was 50 ± 20.4% in t-ALL, and 55.2 ± 11.0% in t-AML. Allogeneic hematopoietic cell transplantation (allo-HCT) was associated with superior 5-year OS (HCT(+) vs. HCT(−), 78.8 vs. 12.1%
p &
lt
0.001), and 26 of 32 patients received allo-HCT in complete remission (CR). Only allo-HCT was associated with superior OS on multivariate analysis (HR 0.003, 95% CI 0.0001–0.098
p &
lt
0.001). These findings suggest that allo-HCT in CR improves pediatric t-leukemia outcomes.

Secondary cancer after a childhood cancer diagnosis: viewpoints considering primary cancer
Yasushi Ishida, Miho Maeda, Souichi Adachi, Hiroko Inada, Hiroshi Kawaguchi, Hiroki Hori, Atsushi Ogawa, Kazuko Kudo, Chikako Kiyotani, Hiroyuki Shichino, Takeshi Rikiishi, Ryoji Kobayashi, Maho Sato, Jun Okamura, Hiroaki Goto, Atsushi Manabe, Shinji Yoshinaga, Dongmei Qiu, Junichiro Fujimoto, Tatsuo Kuroda
International Journal of Clinical Oncology, 1, 11, Springer Tokyo, 2018年06月05日, ［査読有り］
英語, 研究論文（学術雑誌）, Backgrounds: Multidisciplinary therapy has increased the risk of subsequent late effects, but detailed analyses on secondary cancers in childhood cancer survivors (CCSs) are limited in Asian countries. Methods: This was a retrospective cohort study comprising 10,069 CCSs who were diagnosed between 1980 and 2009 across 15 Japanese hospitals. We conducted secondary analyses to estimate the incidence of secondary cancer according to each primary malignancy and to elucidate the association between primary and secondary cancers. We also explored the risk factors for the development of secondary cancer in each independent primary malignancy. Results: The cumulative incidence of secondary cancer at 20 years varied among primary cancers: hematological malignancy, 3.1% (95% CI 2.2–4.3)
retinoblastoma, 6.6% (95% CI 1.5–16.8)
pediatric solid tumor, 2.5% (95% CI 1.3–4.2)
brain tumors, 5.2% (95% CI 1.7–11.8) bone/soft tissue sarcoma, 5.2% (95% CI 2.3–10.1)
and others, 3.3% (95% CI 1.6–6.0) (p = 0.015). The cumulative incidence of secondary cancers is highest in those with osteosarcoma (13.1%) followed by those with hepatoblastoma (8.4%) and retinoblastoma (6.6%). Close association between the primary and secondary cancer diagnoses was found. The risk factors for secondary cancer development depended on the primary cancer, but autologous/allogeneic stem cell transplantation was a relatively common risk factor. Conclusion: The cumulative incidence of secondary cancer varied among primary cancers. The primary cancer was closely associated with the secondary cancer but stem cell transplantation was a common risk factor for secondary cancers among CCSs.

Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on toxicity and antileukemic efficacy.
Rina Nishii, Takaya Moriyama, Laura J Janke, Wenjian Yang, Chase C Suiter, Ting-Nien Lin, Lie Li, Kentaro Kihira, Hidemi Toyoda, Ute Hofmann, Matthias Schwab, Masatoshi Takagi, Tomohiro Morio, Atsushi Manabe, Shirley Kham, Nan Jiang, Karen R Rabin, Motohiro Kato, Katsuyoshi Koh, Allen Eng-Juh Yeoh, Hiroki Hori, Jun J Yang
Blood, 131, 22, 2466, 2474, American Society of Hematology, 2018年05月31日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Thiopurines (eg, 6-mercaptopurine [MP]) are highly efficacious antileukemic agents, but they are also associated with dose-limiting toxicities. Recent studies by us and others have identified inherited NUDT15 deficiency as a novel genetic cause of thiopurine toxicity, and there is a strong rationale for NUDT15-guided dose individualization to preemptively mitigate adverse effects of these drugs. Using CRISPR-Cas9 genome editing, we established a Nudt15-/- mouse model to evaluate the effectiveness of this strategy in vivo. Across MP dosages, Nudt15-/- mice experienced severe leukopenia, rapid weight loss, earlier death resulting from toxicity, and more bone marrow hypocellularity compared with wild-type mice. Nudt15-/- mice also showed excessive accumulation of a thiopurine active metabolite (ie, DNA-incorporated thioguanine nucleotides [DNA-TG]) in an MP dose-dependent fashion, as a plausible cause of increased toxicity. MP dose reduction effectively normalized systemic exposure to DNA-TG in Nudt15-/- mice and largely eliminated Nudt15 deficiency-mediated toxicity. In 95 children with acute lymphoblastic leukemia, MP dose adjustment also directly led to alteration in DNA-TG levels, the effects of which were proportional to the degree of NUDT15 deficiency. Using leukemia-bearing mice with concordant Nudt15 genotype in leukemia and host, we also confirmed that therapeutic efficacy was preserved in Nudt15-/- mice receiving a reduced MP dose compared with Nudt15+/+ counterparts exposed to a standard dose. In conclusion, we demonstrated that NUDT15 genotype-guided MP dose individualization can preemptively mitigate toxicity without compromising therapeutic efficacy.

Risk factors for psychological and psychosomatic symptoms among children with malignancies
Kenichi Maeda, Daisuke Hasegawa, Kevin Y Urayama, Shinichi Tsujimoto, Yuriko Azami, Miwa Ozawa, Atsushi Manabe
Journal of Paediatrics and Child Health, 54, 4, 411, 415, Blackwell Publishing, 2018年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Aim: With increasing survival rates in paediatric malignancies, the quality-of-life of children during hospitalisation should be given more attention. We aimed to identify factors associated with psychological and psychosomatic symptoms (PPS) that required medication among children hospitalised for treatment of malignancies. Methods: We retrospectively analysed data of 190 patients aged 2–18 years old. They were diagnosed with malignant diseases and admitted for treatment at St. Luke's International Hospital between 2003 and 2013. Patients were considered as having PPS if they were prescribed psychotropic agents during hospitalisation. Results: Of the 190 patients, 56 (30%) were prescribed psychotropic agents for PPS. Types of PPS included insomnia in 21 (38%), anxiety in 11 (20%), and others conditions (psychogenetic nausea, agitation, delirium, depression). The most prescribed psychotropic agents were etizolam for 34 cases (61%), followed by diazepam and risperidone. The multivariable analyses confirmed statistically significant independent associations for haematopoietic stem cell transplantation (HSCT) (odds ratio (OR), 5.21
95% confidence interval (CI), 1.77–15.35), older age (12–18 years vs. 2–5 years, OR, 3.74
95% CI, 1.04–10.00), and opioid use (OR, 7.15
95% CI, 2.36–21.69). Conclusions: Older age at admission, undergoing HSCT, and those given opioids were found to be risk factors for PPS among children with malignancies. Appropriate preventive measures against PPS may be warranted for patients with these risk factors.

NUDT15ハプロタイプの6-メルカプトプリン感受性への影響　　　　　　　　　　　　　　　
田中 庸一, 近藤 健介, 康 勝好, 尾鳥 勝也, 真部 淳
日本薬学会年会要旨集, 138年会, 4, 61, 61, (公社)日本薬学会, 2018年03月
日本語

Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia.
Yachiyo Kuwatsuka, Daisuke Tomizawa, Rika Kihara, Yasunobu Nagata, Norio Shiba, Yuka Iijima-Yamashita, Akira Shimada, Takao Deguchi, Hayato Miyachi, Akio Tawa, Takashi Taga, Akitoshi Kinoshita, Hideki Nakayama, Nobutaka Kiyokawa, Akiko Moriya Saito, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Norio Asou, Shigeki Ohtake, Shuichi Miyawaki, Yasushi Miyazaki, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Yoshikazu Ito, Kiyotoshi Imai, Youko Suehiro, Shinichi Kobayashi, Kunio Kitamura, Emiko Sakaida, Seishi Ogawa, Tomoki Naoe, Yasuhide Hayashi, Keizo Horibe, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Hitoshi Kiyoi
International journal of hematology, 107, 2, 201, 210, 2018年02月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in adolescent and young adults (AYAs) are known to differ in younger children and older adults. To clarify the impact of genetic mutations on clinical outcomes of AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies. AYAs aged 15-39 years (n = 103) were included. FLT3-ITD, KIT, CEBPA, NRAS, KRAS, WT1, MLL-PTD, and NPM1 mutations were analyzed. Overall survival (OS) of the AYAs was 61% and event-free survival was 38% at 3 years. FLT3-ITD (HR 2.10; 95% CI 1.07-4.12; p = 0.031) and NPM1 (HR 0.24; 95% CI 0.06-1.00; p = 0.050) mutations were associated with risk of overall mortality in multivariate analysis. OS was significantly different according to FLT3-ITD and NPM1 mutation status (p = 0.03). Survival was 100% with NPM1 mutations in the absence of FLT3-ITD and 35% (95% CI 14-57%) with FLT3-ITD in the absence of NPM1 mutations. The OS of AYAs, children (n = 413) and older adults (n = 124) of the AML-05 and AML201 participants were significantly different (p < 0.0001). This is the first report to combine clinical and genetic data of AYA AML from the major Japanese pediatric and adult study groups.

幼弱T細胞性急性リンパ性白血病の予後因子の検討(Prognostic analysis of immature T-cell acute lymphoblastic leukemia)　　　　　　　　　　　　　　　
木村 俊介, 関 正史, 吉田 健一, 上野 浩生, 大木 健太郎, 小林 良二, 出口 隆生, 橋井 佳子, 今村 俊彦, 佐藤 篤, 清河 信敬, 小林 正夫, 岡 明, 林 泰秀, 真部 淳, 小原 明, 堀部 敬三, 宮野 悟, 小川 誠司, 滝田 順子
日本小児科学会雑誌, 122, 2, 234, 234, (公社)日本小児科学会, 2018年02月, ［査読有り］
英語

小児がん経験者の成人男性の性機能及び性行動に関する検討　　　　　　　　　　　　　　　
相賀 咲央莉, 小澤 美和, 石田 也寸志, 長沖 優子, 伊藤 純子, 吉本 優里, 平林 真介, 細谷 要介, 長谷川 大輔, 真部 淳, 細谷 亮太
日本小児科学会雑誌, 122, 2, 358, 358, (公社)日本小児科学会, 2018年02月
日本語

[Transplantation-associated thrombotic microangiopathy confirmed by renal biopsy].
Miyamoto S, Kimura S, Hosoya Y, Hasegawa D, Ishida H, Daida A, Matsui T, Yoshimoto Y, Hirabayashi S, Fujimaru T, Kumamoto T, Mori SI, Suzuki K, Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 59, 4, 389, 394, 2018年, ［査読有り］

Treatment and biology of pediatric acute lymphoblastic leukemia
Motohiro Kato, Atsushi Manabe
Pediatrics International, 60, 1, 4, 12, Blackwell Publishing, 2018年01月01日, ［査読有り］
英語, Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In the past ALL was intractable but now the survival probability is as high as 80–90%. Improved supportive care, treatment stratification based on relapse risk, biological features of leukemic cells, and optimization of treatment regimens by nationwide and international collaboration have contributed to this dramatic improvement. While including traditional risk factors (e.g. age and leukocyte count at diagnosis), the treatment has been modified based on biological characteristics (aneuploidy and translocation) and treatment response (assessed by minimal residual disease). Treatment for pediatric ALL typically consists of induction therapy with steroids, vincristine, and asparaginase with or without anthracycline, followed by multi-agent consolidation including high-dose methotrexate and re-induction therapy. After consolidation, less intensive maintenance therapy is required for 1–2 years to maintain event-free survival. Recently, using advanced genomic analysis technology, novel sentinel genomic alterations that may provide more precise stratification or therapeutic targets, were identified. Moreover, in the last decade germline variations have been recognized as similarly important contributors to understanding the etiology and sensitivity of ALL to treatment. A more individualized approach based on genomic features (somatic and germline) and treatment response, the introduction of newly developed agents such as molecular targeted drugs or immunotherapy, and social support including long-term follow up are required for further improvement.

小児病棟に入院する小児がんの子どもの生活に対する家族の意識調査
入江 亘, 長谷川 大輔, 神谷 尚宏, 永瀬 恭子, 吉川 久美子, 関冨 晶子, 天野 こころ, 石井 里奈, 芹澤 裕子, 坂本 代喜江, 大野 尚子, 菅家 美和, 田村 妙子, 真部 淳, 石田 也寸志, 平田 美佳, 細谷 亮太
日本小児血液・がん学会雑誌, 55, 1, 7, 14, 日本小児血液・がん学会, 2018年
日本語, 小児がんの子どもは治療のため長期の入院を要するが，入院生活の実態を家族側から検討した研究はほとんどない．そこで，入院生活の実態とそれに対する家族の考えを明らかにするため，家族への横断的質問紙調査を行った．2004年4月から2009年10月の間に当院に入院したことがある43名の小児がんの子どもの家族から回答を得た．22家族（51%）は入院中のテレビ視聴が制限されていると感じていたが，入院前のテレビ視聴時間や子どもの年齢はその感じ方に影響を与えていなかった．テレビ視聴が制限されていると感じる家族は，子どもが気分転換できずにストレスがたまっていると回答していた．携帯電話の所有率は同世代の平均よりも高く，所有していた子どもの半数以上は，入院を契機に購入していた．病院食については，入院中に食事の持ち込みが禁止されていて「困って」いたと回答していた家族の78%が「子どもが病院食を全く食べない」と捉え，持ち込み食を希望する回答が寄せられた．また，家族の63%は子どもの食事の嗜好に変化が生じたと感じており，塩味や濃い味を好む傾向があった．本調査から，病棟規則でメディアや持ち込み食を一律に禁止するよりも上手に利用するメリットがある可能性が示唆された．モバイル機器の進化などにより生活スタイルが日々変化することを考慮し，時代に即した柔軟な対応が小児がんの子どもの入院生活の質向上につながる可能性がある．

Nationwide Survey of Pediatric Hypodiploid Acute Lymphoblastic Leukemia in Japan
Ishimaru Sae, Okamoto Yasuhiro, Imai Chihaya, Sakaguchi Hirotoshi, Taki Tomohiko, Hasegawa Daisuke, Cho Yuko, Kakuda Harumi, Sano Hideki, Manabe Atushi, Imamura Toshihiko, Kato Motohiro, Arakawa Yuki, Shimonodan Hidemi, Sato Atsushi, Suenobu So-ichi, Inukai Takeshi, Watanabe Arata, Kawano Yoshifumi, Kikuta Atsushi, Horibe Keizo, Ohara Akira, Koh Katsuyoshi
BLOOD, 130, 2017年12月07日, ［査読有り］

A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study)
Takashi Kobayashi, Yasuhito Nannya, Motoshi Ichikawa, Kenji Oritani, Yuzuru Kanakura, Akihiro Tomita, Hitoshi Kiyoi, Masayoshi Kobune, Junji Kato, Hiroshi Kawabata, Motohiro Shindo, Yoshihiro Torimoto, Yuji Yonemura, Nobuyoshi Hanaoka, Hideki Nakakuma, Daisuke Hasegawa, Atsushi Manabe, Naohito Fujishima, Nobuharu Fujii, Mitsune Tanimoto, Yasuyoshi Morita, Akira Matsuda, Atsushi Fujieda, Naoyuki Katayama, Haruhiko Ohashi, Hirokazu Nagai, Yoshiki Terada, Masayuki Hino, Ken Sato, Naoshi Obara, Shigeru Chiba, Kensuke Usuki, Masatsugu Ohta, Osamu Imataki, Makiko Uemura, Tomoiku Takaku, Norio Komatsu, Akira Kitanaka, Kazuya Shimoda, Kenichiro Watanabe, Kaoru Tohyama, Akifumi Takaori-Kondo, Hideo Harigae, Shunya Arai, Yasushi Miyazaki, Keiya Ozawa, Mineo Kurokawa
AMERICAN JOURNAL OF HEMATOLOGY, 92, 12, 1324, 1332, WILEY, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences. The overall survival (OS) and AML progression-free survival (AML-PFS) of hMDS were higher than those of non-hMDS, especially in patients at age 50 and of lower risk in Revised International Prognostic Scoring System (IPSS-R). In competing risks analysis, hMDS exhibited decreased risk of AML-progression in lower IPSS or IPSS-R risk patients, and higher risk of death from BMF in patients at age 50. Poor performance status (PS 2) and high karyotype risks in IPSS-R (high and very high) were significant risk factors of death and AML-progression in Cox proportional hazards analysis.

Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia
Shinsuke Hirabayashi, Masafumi Seki, Daisuke Hasegawa, Motohiro Kato, Nobuyuki Hyakuna, Takuya Shuo, Shunsuke Kimura, Kenichi Yoshida, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Nobutaka Kiyokawa, Satoru Miyano, Seishi Ogawa, Junko Takita, Atsushi Manabe
PEDIATRIC BLOOD & CANCER, 64, 12, WILEY, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Maffucci syndrome is a nonhereditary disorder caused by somatic mosaic isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations and is characterized by multiple enchondromas along with hemangiomas. Malignant transformation of enchondromas to chondrosarcomas and secondary neoplasms, such as brain tumors or acute myeloid leukemia, are serious complications. A 15-year-old female with Maffucci syndrome developed B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A somatic mutation in IDH1 was detected in hemangioma and leukemic cells. KRAS mutation and deletion of IKZF1 were detected in leukemic cells. Patients with Maffucci syndrome may, therefore, be at risk of BCP-ALL associated with secondary genetic events that affect lymphocyte differentiation.

AYA世代小児がん経験者の為の包括的ドックからの報告 食行動と生活習慣病への看護介入の必要性
前田 邦枝, 永瀬 恭子, 郡司 美千代, 小林 京子, 細谷 要介, 小澤 美和, 長谷川 大輔, 真部 淳, 石田 也寸志
日本小児血液・がん学会雑誌, 54, 4, 429, 429, (一社)日本小児血液・がん学会, 2017年10月
日本語

AYA世代小児がん経験者の長期フォローアップにおける自立支援ケア計画の視点と目標 実践報告
郡司 美千代, 永瀬 恭子, 小林 京子, 前田 邦枝, 小澤 美和, 細谷 要介, 長谷川 大輔, 真部 淳, 細谷 亮太, 石田 也寸志
日本小児血液・がん学会雑誌, 54, 4, 430, 430, (一社)日本小児血液・がん学会, 2017年10月
日本語

Plasma asparaginase activity, asparagine concentration, and toxicity after administration of Erwinia asparaginase in children and young adults with acute lymphoblastic leukemia: Phase I/II clinical trial in Japan
Chitose Ogawa, Fumi Taguchi, Hiroaki Goto, Katsuyoshi Koh, Daisuke Tomizawa, Akira Ohara, Atsushi Manabe
PEDIATRIC BLOOD & CANCER, 64, 9, WILEY, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）, BackgroundA phase I/II study of Erwinia asparaginase in Japanese children and young adults with acute lymphoblastic leukemia (ALL) was performed to investigate its activity and toxicity.
ProcedureEligible patients were in remission and had developed allergy to Escherichia coli asparaginase. Erwina asparaginase was intramuscularly administrated on days 2, 5, 7, 9, 11, and 13. To measure the plasma l-asparagine concentration (PAC), amino acids were derivatized with N-(5-fluoro-2,4-dinitrophenyl)-l-leucinamide.
ResultsSix consecutive patients completed the phase I study with 25,000 IU/m(2) per dose without dose-limiting toxicity and 18 patients completed the phase II study with 25,000 IU/m(2) per dose. Median age of 24 patients was 7.5 (range 2-16) years. The half-life of plasma asparaginase activity (PAA) was 16.9 7.5 hr and the maximum PAA was 3.10 +/- 1.47 IU/ml (n = 23, noncompartment model). PAA of 0.1 IU/ml or more was achieved in all 23 patients (100%) 48 hr and in 18 of 23 patients (78.3%) 72 hr after the first administration. During the 2-week study, 94.2% (65 of 69) of the 48-hr samples and 80.4% (37 of 46) of the 72-hr samples had PAA of 0.1 IU/ml or more. PAC less than 1.0 M was achieved in 95.7% patients 48 and 72 hr after administration. PAC values in all the samples were greater than the limit of quantitation (0.0625 M). Karnofsky performance status of all patients was good during the 2-week study.
ConclusionsErwinia asparaginase 25,000 IU/m(2) per dose x six intramuscular administrations in 2 weeks was well tolerated, pharmacologically efficacious, and safe in Japanese patients with ALL/lymphoblastic lymphoma.

Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia
Masafumi Seki, Shunsuke Kimura, Tomoya Isobe, Kenichi Yoshida, Hiroo Ueno, Yaeko Nakajima-Takagi, Changshan Wang, Lin Lin, Ayana Kon, Hiromichi Suzuki, Yusuke Shiozawa, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Kyoko Masuda, Hiroshi Kawamoto, Kentaro Ohki, Motohiro Kato, Yuki Arakawa, Katsuyoshi Koh, Ryoji Hanada, Hiroshi Moritake, Masaharu Akiyama, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Akira Oka, Yasuhide Hayashi, Masatoshi Takagi, Atsushi Manabe, Akira Ohara, Keizo Horibe, Masashi Sanada, Atsushi Iwama, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Junko Takita
NATURE GENETICS, 49, 8, 1274, +, NATURE PUBLISHING GROUP, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor(1), and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric TALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN; CD4(-)CD8(-)) or CD8(+) single-positive (SP) phenotype and had uniformly poor overall survival. These cases represent a subset of pediatric T-ALL distinguishable from the known T-ALL subsets(2) in terms of expression of genes involved in T cell precommitment, establishment of T cell identity, and post-beta-selection maturation and with respect to mutational profile. PU.1 fusion proteins retained transcriptional activity and, when constitutively expressed in mouse stem/progenitor cells, induced cell proliferation and resulted in a maturation block. Our findings highlight a unique role of SPI1 fusions in high-risk pediatric T-ALL.

Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia
Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita, Tadashi Ariga, Yosuke Hosoya, Shinsuke Hirabayashi, Atsushi Manabe, Keisuke Hara, Tetsuya Aiba, Tsugumi Shiokawa, Hiroko Tada, Norihiro Sato
INTERNATIONAL JOURNAL OF HEMATOLOGY, 106, 2, 291, 298, SPRINGER JAPAN KK, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib (1.3 mg/m(2)/dose) combined with two standard induction chemotherapies was used. Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six patients developed severe infectious complications. Peripheral neuropathy (grade 2) occurred in five patients. The individual plasma bortezomib concentration-time profiles were not related to toxicity and efficacy. Five patients were evaluable for response, and four patients achieved complete response (CR) or CR without platelet recovery (80%). In conclusion, four-dose bortezomib (1.3 mg/m(2)/dose) combined with standard re-induction chemotherapy was associated with a high risk of infectious complications induced by prolonged neutropenia, although high efficacy has been achieved for Japanese pediatric patients with refractory ALL. Attention must be given to severe infectious complications when performing re-induction chemotherapy including bortezomib.

EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells
Akinori Yaguchi, Takeshi Ishibashi, Kazuki Terada, Hitomi Ueno-Yokohata, Yuya Saito, Junya Fujimura, Toshiaki Shimizu, Kentaro Ohki, Atsushi Manabe, Nobutaka Kiyokawa
INTERNATIONAL JOURNAL OF HEMATOLOGY, 106, 2, 269, 281, SPRINGER JAPAN KK, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, ZNF384-related fusion genes are associated with a distinct subgroup of B-cell precursor acute lymphoblastic leukemias in childhood, with a frequency of approximately 3-4%. We previously identified a novel EP300-ZNF384 fusion gene. Patients with the ZNF384-related fusion gene exhibit a hematopoietic stem cell (HSC) gene expression signature and characteristic immunophenotype with negative or low expression of CD10 and aberrant expression of myeloid antigens, such as CD33 and CD13. However, the molecular basis of this pathogenesis remains completely unknown. In the present study, we examined the biological effects of EP300-ZNF384 expression induced by retrovirus- mediated gene transduction in an REH B-cell precursor acute lymphoblastic leukemia cell line, and observed the acquisition of the HSC gene expression signature and an up-regulation of GATA3 gene expression, as assessed by microarray analysis. In contrast, the gene expression profile induced by wild-type ZNF384 in REH cells was significantly different from that by EP300-ZNF384 expression. Together with the results of reporter assays, which revealed the enhancement of GATA3-promoter activity by EP300-ZNF384 expression, these findings suggest that EP300-ZNF384 mediates GATA3 gene expression and may be involved in the acquisition of the HSC gene expression signature and characteristic immunophenotype in B-cell precursor acute lymphoblastic leukemia cells.

Salvage therapy for children with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia
Yuichi Kodama, Atsushi Manabe, Hirohide Kawasaki, Itaru Kato, Keisuke Kato, Atsushi Sato, Kimikazu Matsumoto, Motohiro Kato, Hidefumi Hiramatsu, Hideki Sano, Takashi Kaneko, Megumi Oda, Akiko M. Saito, Souichi Adachi, Keizo Horibe, Shuki Mizutani, Eiichi Ishii, Hiroyuki Shimada
PEDIATRIC BLOOD & CANCER, 64, 8, WILEY, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, BackgroundIn the tyrosine kinase inhibitor (TKI) era, outcomes after salvage therapy for relapsed or refractory Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remain unclear.
ProcedureThe clinical courses of 19 patients with relapse (n = 13) or induction failure (n = 6) in the Japanese Pediatric Leukemia/Lymphoma Study Group Ph+ ALL04 study were retrospectively reviewed.
ResultsFifteen male and four female patients had a median age of 8 (range 4-15) years at relapse or induction failure. Patients received imatinib in combination with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and methotrexate and cytarabine (MTX/Ara-C) (n = 9), imatinib in combination with other chemotherapy (n = 5), chemotherapy without imatinib (n = 2), imatinib alone (n = 2), or no additional chemotherapy (n = 1). Two patients underwent hematopoietic stem cell transplantation (HSCT) without achieving complete remission (CR) and died of leukemia. The remaining 17 patients achieved CR with salvage therapies and underwent HSCT whilst in CR: 10 patients remain alive in CR, five died of transplantation-related complications, and two died of relapse. In six of seven patients with available data on minimal residual disease (MRD), imatinib in combination with the first course of hyper-CVAD was more effective in achieving a favorable MRD response compared with the Ph+ ALL04 induction regimen.
ConclusionThis study suggested that cross-resistance to imatinib failed to develop after conventional chemotherapy. Imatinib in combination with chemotherapy including hyper-CVAD+MTX/Ara-C was effective and safe for relapsed or refractory Ph+ ALL patients who received frontline therapy without imatinib.

Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia
Masafumi Seki, Shunsuke Kimura, Tomoya Isobe, Kenichi Yoshida, Hiroo Ueno, Yaeko Nakajima-Takagi, Changshan Wang, Lin Lin, Ayana Kon, Hiromichi Suzuki, Yusuke Shiozawa, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Kyoko Masuda, Hiroshi Kawamoto, Kentaro Ohki, Motohiro Kato, Yuki Arakawa, Katsuyoshi Koh, Ryoji Hanada, Hiroshi Moritake, Masaharu Akiyama, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Akira Oka, Yasuhide Hayashi, Masatoshi Takagi, Atsushi Manabe, Akira Ohara, Keizo Horibe, Masashi Sanada, Atsushi Iwama, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Junko Takita
Nature Genetics, 49, 8, 1274, 1281, Nature Publishing Group, 2017年08月01日, ［査読有り］
英語, 研究論文（学術雑誌）, The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN
CD4 - CD8 -) or CD8 + single-positive (SP) phenotype and had uniformly poor overall survival. These cases represent a subset of pediatric T-ALL distinguishable from the known T-ALL subsets in terms of expression of genes involved in T cell precommitment, establishment of T cell identity, and post-β-selection maturation and with respect to mutational profile. PU.1 fusion proteins retained transcriptional activity and, when constitutively expressed in mouse stem/progenitor cells, induced cell proliferation and resulted in a maturation block. Our findings highlight a unique role of SPI1 fusions in high-risk pediatric T-ALL.

Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes
Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Sayoko Doisaki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Masashi Sanada, Yoshiyuki Takahashi, Hitoshi Kanno, Hiroki Yamaguchi, Shouichi Ohga, Atsushi Manabe, Hideo Harigae, Shinji Kunishima, Eiichi Ishii, Masao Kobayashi, Kenichi Koike, Kenichiro Watanabe, Etsuro Ito, Minoru Takata, Miharu Yabe, Seishi Ogawa, Satoru Miyano, Seiji Kojima
GENETICS IN MEDICINE, 19, 7, 796, 802, NATURE PUBLISHING GROUP, 2017年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Precise genetic diagnosis of inherited bone marrow failure syndromes (IBMFS), a heterogeneous group of genetic disorders, is challenging but essential for precise clinical decision making.
Methods: We analyzed 121 IBMFS patients using a targeted sequencing covering 184 associated genes and 250 IBMFS patients using whole-exome sequencing (WES).
Results: We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES. In the majority of cases (targeted sequencing: 45/53, 85%; WES: 63/68, 93%), the detected variants were concordant with, and therefore supported, the clinical diagnoses. However, in the remaining 13 cases (8 patients by target sequencing and 5 patients by WES), the clinical diagnoses were incompatible with the detected variants.
Conclusion: Our approach utilizing targeted sequencing and WES achieved satisfactory diagnostic rates and supported the efficacy of massive parallel sequencing as a diagnostic tool for IBMFS.

Myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML)
Daisuke Hasegawa, Atsushi Manabe
Hematological Disorders in Children: Pathogenesis and Treatment, 87, 108, Springer Singapore, 2017年06月14日, ［査読有り］
英語, 論文集(書籍)内論文, Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorders and is uncommon in children comparing to adults. According to the proportion of blasts in the bone marrow (BM) and peripheral blood, it is divided into low-grade MDS and advanced MDS. Low-grade MDS often shows hypocellular BM, which makes differentiation from aplastic anemia and inherited bone marrow failure syndrome challenging. Treatment strategy for low-grade MDS should be determined based on the severity of cytopenias, karyotypes, and donor availability. In advanced MDS, two-thirds have chromosomal aberrations such as monosomy 7, and acute myeloid leukemia (AML) is the major differential diagnosis. Allogeneic hematopoietic cell transplantation (HCT) is the mainstay of treatment for children with advanced MDS
however, relapse and transplant-related mortality are obstacle to cure. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloid neoplasm of early childhood characterized by excessive proliferation of monocytic and granulocytic cells. The hypersensitivity of myeloid progenitor cells to GM-CSF is regarded as a hallmark of JMML and is caused by mutations in genes regulating the RAS signaling pathway (i.e., NRAS, KRAS, NF1, PTPN11, and CBL). Although allogeneic HCT is the treatment of choice for most patients with JMML, a subset of patients harboring mutations in CBL or RAS can be managed without HCT.

The effects of inherited NUDT15 polymorphisms on thiopurine active metabolites in Japanese children with acute lymphoblastic leukemia
Takaya Moriyama, Rina Nishii, Ting-Nien Lin, Kentaro Kihira, Hidemi Toyoda, Nersting Jacob, Motohiro Kato, Katsuyoshi Koh, Hiroto Inaba, Atsushi Manabe, Kjeld Schmiegelow, Jun J. Yang, Hiroki Hori
PHARMACOGENETICS AND GENOMICS, 27, 6, 236, 239, LIPPINCOTT WILLIAMS & WILKINS, 2017年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting hematopoietic toxicity. Recently, germline variants in NUDT15 have been identified as a major genetic cause for MP-related bone marrow suppression, and there is increasing interest in the clinical implementation of NUDT15 genotype-guided MP dose individualization. Therefore, we sought to evaluate the effects of NUDT15 on thiopurine metabolism and identify pharmacologic markers to inform NUDT15 genotype-guided MP dosing. In 55 Japanese children with acute lymphoblastic leukemia, we simultaneously measured both thioguanine nucleotides (TGN) in red blood cells and DNA-incorporated thioguanine (DNA-TG) in white blood cells. TGN levels were significantly lower in patients with NUDT15 deficiency, likely because of toxicity-related MP dose reduction. In contrast, when exposed to the same dose of MP, DNA-TG accumulated more efficiently in vivo with increasing number of risk alleles in NUDT15 (P=4.0x10(-9)). Cytosolic TGN and nuclear DNA-TG were correlated positively with each other across genotype groups (P=6.5x10(-4)), but the ratio of DNA-TG to TGN was significantly higher in NUDT15-deficient patients (P=3.6x10(-9)), consistent with excessive MP activation. In conclusion, our results suggest that DNA-TG is a more relevant MP metabolite than TGN to inform NUDT15 genotype-guided dose adjustments.

ZNF384関連融合遺伝子はALLの細胞マーカーに特徴を有する亜群を規定する　　　　　　　　　　　　　　　
清河 信敬, 大木 健太郎, 平林 真介, 福島 敬, 康 勝好, 真部 淳, 小原 明
Cytometry Research, 27, Suppl., 64, 64, (一社)日本サイトメトリー学会, 2017年06月
日本語

Risk Factors for Hospital-acquired Clostridium difficile Infection Among Pediatric Patients With Cancer
Atsuro Daida, Hiroki Yoshihara, Ikuko Inai, Daisuke Hasegawa, Yasushi Ishida, Kevin Y. Urayama, Atsushi Manabe
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 39, 3, E167, E172, LIPPINCOTT WILLIAMS & WILKINS, 2017年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Hospital-acquired Clostridium difficile infection (CDI) may cause life-threatening colitis for children with cancer, making identification of risk factors important. We described characteristics of pediatric cancer patients with primary and recurring CDI, and evaluated potential risk factors. Among 189 cancer patients, 51 cases (27%) of CDI and 94 matched controls of cancer patients without CDI were analyzed. Multivariable logistic regression was used to evaluate the association between CDI and several potential risk factors. Median age of CDI cases was lower (3.3 y; 0.60 to 16.2) than controls (7.7 y; 0.4 to 20.5). Median duration of neutropenia before CDI was longer for CDI cases (10.0 d; 0.0 to 30.0) compared with duration calculated from reference date in controls (6.0 d; 0.0 to 29.0). Multivariable analysis showed that older age was associated with reduced risk (>= 7 vs. 0 to 3 y, odds ratio=0.11; 95% confidence interval, 0.02-0.54), and prolonged neutropenia was associated with increased risk (odds ratio=1.11; 95% confidence interval, 1.01-1.22). CDI recurred in 26% of cases. Younger age and prolonged neutropenia were risk factors for CDI in children with cancer. Increasing awareness to these risk factors will help to identify opportunities for CDI prevention in cancer patients.

Interaction between NUDT15 and ABCC4 variants enhances intolerability of 6-mercaptopurine in Japanese patients with childhood acute lymphoblastic leukemia.
Tanaka Y, Nakadate H, Kondoh K, Nakamura K, Koh K, Manabe A
The pharmacogenomics journal, 2017年04月, ［査読有り］

Infantile fibrosarcoma treated with postoperative vincristine and dactinomycin
Hiroki Yoshihara, Yuri Yoshimoto, Yosuke Hosoya, Daisuke Hasegawa, Takafumi Kawano, Akiko Sakoda, Hajime Okita, Atsushi Manabe
PEDIATRICS INTERNATIONAL, 59, 3, 371, 374, WILEY, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Infantile fibrosarcoma is a non-rhabdomyosarcoma soft-tissue sarcoma that occurs in infancy and which has a relatively good prognosis. A vincristine and dactinomycin (VA) regimen has been shown to be effective, although the duration of chemotherapy has not been well defined. We describe the case of a 4-month-old boy with a mass at the left dorsum of the foot who was diagnosed with infantile fibrosarcoma after resection of the tumor, the margin of which was macroscopically positive. VA treatment was carried out with careful monitoring of response and adverse effects. Pancytopenia was seen during the second cycle, and therapy was reduced thereafter. The treatment was continued for 38 weeks (12 cycles). There was no functional impairment, and no evidence of recurrence at 18 months after therapy.

Pediatric intestinal Behçet disease complicated by myeloid malignancies.
Kanamitsu K, Shimada A, Nishiuchi R, Shigemura T, Nakazawa Y, Koike K, Kodama Y, Shinkoda Y, Kawano Y, Yasui K, Sasaki K, Kajiwara R, Tsukahara H, Manabe A
International journal of hematology, 105, 3, 377, 382, SPRINGER JAPAN KK, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Beh double dagger et disease (BD) is rarely seen in children. Its clinical manifestations are believed to differ between pediatric and adult patients. The characteristics of BD complicated by myelodysplastic syndrome (MDS) are well established for adult patients; however, because only a few cases of pediatric-onset BD complicated by MDS have been reported, its clinical characteristics remain unknown. We here retrospectively review pediatric-onset BD complicated by myeloid malignancies in Japan, having identified five such patients. All patients were female and had gastrointestinal involvements, but lacked both major features of BD, i.e., uveitis and association with HLA-B51. All patients had advanced MDS or acute myeloid leukemia and received chemotherapy followed by hematopoietic stem cell transplantation. These five cases suggest that intestinal BD and myeloid malignancies have one or more pathophysiological mechanisms in common.

小児急性リンパ性白血病患児における高用量メトトレキサート投与後の血中濃度に影響を与える因子の検討　　　　　　　　　　　　　　　
田中 庸一, 浦山 ケビン, 森 麻希子, 長谷川 大輔, 太田 節雄, 柳町 昌克, 康 勝好, 尾鳥 勝也, 真部 淳
日本薬学会年会要旨集, 137年会, 4, 176, 176, (公社)日本薬学会, 2017年03月, ［査読有り］
日本語

Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.
M Kato, S Ishimaru, M Seki, K Yoshida, Y Shiraishi, K Chiba, N Kakiuchi, Y Sato, H Ueno, H Tanaka, T Inukai, D Tomizawa, D Hasegawa, T Osumi, Y Arakawa, T Aoki, M Okuya, K Kaizu, K Kato, Y Taneyama, H Goto, T Taki, M Takagi, M Sanada, K Koh, J Takita, S Miyano, S Ogawa, A Ohara, M Tsuchida, A Manabe
Leukemia, 31, 3, 580, 584, 2017年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children
M. Kato, S. Ishimaru, M. Seki, K. Yoshida, Y. Shiraishi, K. Chiba, N. Kakiuchi, Y. Sato, H. Ueno, H. Tanaka, T. Inukai, D. Tomizawa, D. Hasegawa, T. Osumi, Y. Arakawa, T. Aoki, M. Okuya, K. Kaizu, K. Kato, Y. Taneyama, H. Goto, T. Taki, M. Takagi, M. Sanada, K. Koh, J. Takita, S. Miyano, S. Ogawa, A. Ohara, M. Tsuchida, A. Manabe
LEUKEMIA, 31, 3, 580, 584, NATURE PUBLISHING GROUP, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0 +/- 2.8%. Females (n= 138) had better DFS (74.6 +/- 3.7%) than males (n= 142, 57.5 +/- 4.2%, P= 0.002). Patients with TCF3-PBX1 (n= 11) and ETV6-RUNX1 (n= 16) had excellent DFS (90.9 +/- 8.7% and 93.8 +/- 6.1%, respectively), whereas high hyperdiploidy (n= 23) was the most unfavorable subgroup, with 56.6 +/- 10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

Haploidentical hematopoietic cell transplantation for disseminated Ewing sarcoma
Hiroki Yoshihara, Tadashi Kumamoto, Rintaro Ono, Keiko Akahane, Taiki Nozaki, Shogo Kobayashi, Atsushi Kikuta, Seiichi Matsumoto, Daisuke Hasegawa, Chitose Ogawa, Atsushi Manabe
PEDIATRICS INTERNATIONAL, 59, 2, 223, 226, WILEY, 2017年02月, ［査読有り］
英語, 研究論文（学術雑誌）, We describe the case of a 13-year-old girl with multifocal disseminated Ewing sarcoma family of tumor (ESFT) who received a 5/8 human leukocyte antigen-matched haploidentical hematopoietic cell transplantation to generate a graft-versus-tumor effect. The patient had grade 2 acute graft-versus-host disease (GVHD) of the skin and chronic GVHD nausea and abdominal pain that required prednisolone for 17 months, but has been free from ESFT for 3 years 10 months after therapy. The present case suggests a beneficial effect of haploidentical hematopoietic cell transplantation in disseminated ESFT.

小児白血病における血液凝固障害に対する支持療法 JPLSGアンケート調査　　　　　　　　　　　　　　　
大曽根 眞也, 福島 啓太郎, 矢野 道広, 嘉数 真理子, 佐野 弘純, 加藤 陽子, 新小田 雄一, 篠田 邦大, 真部 淳, 足立 壮一
日本小児科学会雑誌, 121, 2, 251, 251, (公社)日本小児科学会, 2017年02月
日本語

小児白血病診療時の中心静脈カテーテルの使用・管理法 JPLSGアンケート調査　　　　　　　　　　　　　　　
佐野 弘純, 福島 啓太郎, 矢野 道広, 大曽根 眞也, 嘉数 真理子, 加藤 陽子, 新小田 雄一, 篠田 邦大, 真部 淳, 足立 壮一, 日本小児白血病リンパ腫研究グループ
日本小児科学会雑誌, 121, 2, 467, 467, (公社)日本小児科学会, 2017年02月
日本語

小児白血病における抗腫瘍薬の急性毒性に対する対策の現状 JPLSGアンケート調査　　　　　　　　　　　　　　　
矢野 道広, 福島 啓太郎, 佐野 弘純, 大曽根 眞也, 嘉数 真理子, 加藤 陽子, 新小田 雄一, 篠田 邦大, 真部 淳, 足立 壮一, 日本小児白血病リンパ腫研究グループ
日本小児科学会雑誌, 121, 2, 467, 467, (公社)日本小児科学会, 2017年02月
日本語

Familial hematological malignancies.
Shinsuke Hirabayashi, Atsushi Manabe
[Rinsho ketsueki] The Japanese journal of clinical hematology, 58, 10, 1878, 1883, 2017年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. The study of cancer genomes has identified inherited genetic drivers that predispose cancer cells to clonal evolution. The revisions in the categories of myeloid neoplasms and acute leukemia were published as a monograph in 2016. We described familial hematological malignancies using the 2016 edition of the WHO classification.

Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors.
Tsuchiya N, Hosono A, Yoshikawa T, Shoda K, Nosaka K, Shimomura M, Hara J, Nitani C, Manabe A, Yoshihara H, Hosoya Y, Kaneda H, Kinoshita Y, Kohashi K, Yoshimura K, Fujinami N, Saito K, Mizuno S, Nakatsura T
Oncoimmunology, 7, 1, e1377872, 2017年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The carcinoembryonic antigen glypican-3 (GPC3) is a good target of anticancer immunotherapy against pediatric solid tumors expressing GPC3. In this non-randomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3-peptide vaccination in patients with pediatric solid tumors. Eighteen patients with pediatric solid tumors expressing GPC3 underwent GPC3-peptide vaccination (intradermal injections every 2 weeks), with the primary endpoint being the safety of GPC3-peptide vaccination and the secondary endpoints being immune response, as measured by interferon (IFN)-γ enzyme-linked immunospot assay and Dextramer staining, and the clinical outcomes of tumor response, progression free survival (PFS), and overall survival (OS). Our findings indicated that GPC3 vaccination was well tolerated. We observed disease-control rates [complete response (CR)+partial response+stable disease] of 66.7% after 2 months, and although patients in the progression group unable to induce GPC3-peptide-specific cytotoxic T lymphocytes (CTLs) received poor prognoses, patients in the partial-remission and remission groups or those with hepatoblastoma received good prognoses. The GPC3-peptide vaccine induced a GPC3-specific CTL response in seven patients, with PFS and OS significantly longer in patients with high GPC3-specific CTL frequencies than in those with low frequencies. Furthermore, we established GPC3-peptide-specific CTL clones from a resected-recurrent tumor from one patient, with these cells exhibiting GPC3-peptide-specific cytokine secretion. The results of this trial demonstrated that the GPC3-peptide-specific CTLs induced by the GPC3-peptide vaccine infiltrated tumor tissue, and use of the GPC3-peptide vaccine might prevent the recurrence of pediatric solid tumors, especially hepatoblastomas, after a second CR.

ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype
Shinsuke Hirabayashi, Kentaro Ohki, Kazuhiko Nakabayashi, Hitoshi Ichikawa, Yukihide Momozawa, Kohji Okamura, Akinori Yaguchi, Kazuki Terada, Yuya Saito, Ai Yoshimi, Hiroko Ogata-Kawata, Hiromi Sakamoto, Motohiro Kato, Junya Fujimura, Moeko Hino, Akitoshi Kinoshita, Harumi Kakuda, Hidemitsu Kurosawa, Keisuke Kato, Ryosuke Kajiwara, Koichi Moriwaki, Tsuyoshi Morimoto, Kozue Nakamura, Yasushi Noguchi, Tomoo Osumi, Kazuo Sakashita, Junko Takita, Yuki Yuza, Koich Matsuda, Teruhiko Yoshida, Kenji Matsumoto, Kenichiro Hata, Michiaki Kubo, Yoichi Matsubara, Takashi Fukushima, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara, Nobutaka Kiyokawa
HAEMATOLOGICA, 102, 1, 118, 129, FERRATA STORTI FOUNDATION, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners.

ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype.
Shinsuke Hirabayashi, Kentaro Ohki, Kazuhiko Nakabayashi, Hitoshi Ichikawa, Yukihide Momozawa, Kohji Okamura, Akinori Yaguchi, Kazuki Terada, Yuya Saito, Ai Yoshimi, Hiroko Ogata-Kawata, Hiromi Sakamoto, Motohiro Kato, Junya Fujimura, Moeko Hino, Akitoshi Kinoshita, Harumi Kakuda, Hidemitsu Kurosawa, Keisuke Kato, Ryosuke Kajiwara, Koichi Moriwaki, Tsuyoshi Morimoto, Kozue Nakamura, Yasushi Noguchi, Tomoo Osumi, Kazuo Sakashita, Junko Takita, Yuki Yuza, Koich Matsuda, Teruhiko Yoshida, Kenji Matsumoto, Kenichiro Hata, Michiaki Kubo, Yoichi Matsubara, Takashi Fukushima, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara, Nobutaka Kiyokawa
Haematologica, 102, 1, 118, 129, 2017年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384 Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners.

Pediatric thromboembolism: a national survey in Japan
Akira Ishiguro, Chibueze Chioma Ezinne, Nobuaki Michihata, Hisaya Nakadate, Atsushi Manabe, Masashi Taki, Midori Shima
INTERNATIONAL JOURNAL OF HEMATOLOGY, 105, 1, 52, 58, SPRINGER JAPAN KK, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Thromboembolism is being detected at increasing rates in pediatric tertiary care hospitals. The incidence of pediatric thrombophilia differs across countries, and is unknown in Japan. We sent a survey to 520 pediatric department heads and 629 specialists, requesting details on patients who developed symptomatic thromboembolism between 2006 and 2010. Of 280 eligible cases, congenital thrombophilia and other conditions were reported. Congenital thrombophilia (n = 54, 19.3 %) comprised defects in protein C (27), protein S (9), and antithrombin (7). None had mutations in factor V Leiden or prothrombin G20210A, both of which are frequent in Caucasians. Non-congenital causes of thrombophilia included congenital heart disease, the use of central venous catheters, nephrotic syndrome, antiphospholipid syndrome, and malignancy with or without use of L-asparaginase. Patients with congenital thrombophilia developed thromboembolism at a significantly younger age (median 1.0 vs. 5.0 years, p = 0.014), had a higher frequency of consanguinity (35.2 vs. 1.8 %, p < 0.001) and post-thrombotic syndromes (29.6 vs. 13.3 %, p = 0.007) than those who did not. Thromboembolism in children with congenital thrombophilia recurred more frequently (50.0 vs. 13.7 %, p < 0.001) and was associated with more sequelae (61.1 vs. 37.2 %, p = 0.009) than in children without congenital thrombophilia. This nationwide survey provides the first comprehensive study of Japanese children with symptomatic thromboembolism. Significant recurrence and sequelae require optimized standards.

Chemotherapy for a child with relapsed acute myeloid leukemia complicated with persistent hepatitis C virus infection.
Shunsuke Kimura, Shinsuke Hirabayashi, Daisuke Hasegawa, Wakako Sumiya, Megumi Seya, Toshihiro Matsui, Yuri Yoshimoto, Yosuke Hosoya, Nobuyoshi Mori, Akira Matsui, Atsushi Manabe
[Rinsho ketsueki] The Japanese journal of clinical hematology, 58, 6, 619, 623, 2017年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, An 8-year-old Mongolian female was diagnosed with acute myeloid leukemia (AML) and treated at a hospital in Mongolia according to the BFM-AML2004 SR protocol. Although complete remission (CR) was achieved, chemotherapy was interrupted because of shortage of drugs. The patient moved to Japan 7 months after diagnosis. Screening for viral infection revealed the presence of hepatitis C virus (HCV) antibody and RNA. At 11 months after initial diagnosis, the patient experienced bone marrow relapse and a RUNX1-RUNX1T1 fusion transcript was detected. Considering the inadequate intensity of initial treatment and the persistent HCV infection, chemotherapy was preferred and initiated over hematopoietic cell transplantation. After the first course of induction therapy, a second CR was confirmed and the chimeric transcript disappeared. The viral load mildly increased during myelosuppression and transient elevation of liver enzymes was observed along with hematological recovery. HCV infection remained stable, without progression to reactivation of hepatitis C. Given the high risk of second relapse and liver fibrosis and sclerosis following chronic HCV infection, treatment against HCV may be indicated during second remission.

Pediatric thromboembolism: a national survey in Japan
Akira Ishiguro, Chibueze Chioma Ezinne, Nobuaki Michihata, Hisaya Nakadate, Atsushi Manabe, Masashi Taki, Midori Shima
International Journal of Hematology, 105, 1, 52, 58, Springer Tokyo, 2017年01月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Thromboembolism is being detected at increasing rates in pediatric tertiary care hospitals. The incidence of pediatric thrombophilia differs across countries, and is unknown in Japan. We sent a survey to 520 pediatric department heads and 629 specialists, requesting details on patients who developed symptomatic thromboembolism between 2006 and 2010. Of 280 eligible cases, congenital thrombophilia and other conditions were reported. Congenital thrombophilia (n = 54, 19.3 %) comprised defects in protein C (27), protein S (9), and antithrombin (7). None had mutations in factor V Leiden or prothrombin G20210A, both of which are frequent in Caucasians. Non-congenital causes of thrombophilia included congenital heart disease, the use of central venous catheters, nephrotic syndrome, antiphospholipid syndrome, and malignancy with or without use of L-asparaginase. Patients with congenital thrombophilia developed thromboembolism at a significantly younger age (median 1.0 vs. 5.0 years, p = 0.014), had a higher frequency of consanguinity (35.2 vs. 1.8 %, p <
 0.001) and post-thrombotic syndromes (29.6 vs. 13.3 %, p = 0.007) than those who did not. Thromboembolism in children with congenital thrombophilia recurred more frequently (50.0 vs. 13.7 %, p <
 0.001) and was associated with more sequelae (61.1 vs. 37.2 %, p = 0.009) than in children without congenital thrombophilia. This nationwide survey provides the first comprehensive study of Japanese children with symptomatic thromboembolism. Significant recurrence and sequelae require optimized standards.

The Association Between L-Asparaginase Hypersensitivity and Genetic Variants in Japanese Childhood ALL Patients
Yoichi Tanaka, Kevin Y. Urayama, Takahisa Kawaguchi, Makiko Mori, Daisuke Hasegawa, Sae Ishimaru, Yuichi Taneyama, Kazuki Terada, Masakatsu Yanagimachi, Setsuo Ota, Hiroyuki Takahashi, Takeshi Inukai, Daisuke Toyama, Dai Keino, Koichi Moriwaki, Masatoshi Takagi, Junya Fujimura, Yujin Sekinaka, Kozue Nakamura, Yuya Sato, Keitaro Matsuo, Akira Ohara, Katsuyoshi Koh, Fumihiko Matsuda, Atsushi Manabe
BLOOD, 128, 22, AMER SOC HEMATOLOGY, 2016年12月, ［査読有り］
英語, 0

再発神経芽腫において獲得された片親性ダイソミーによるALK遺伝子のホモ変異(Homozygous missense mutation in ALK gene due to acquired uniparental disomy in a child with relapsed neuroblastoma)
木村 俊介, 長谷川 大輔, 代田 惇朗, 関 正史, 吉本 優里, 平林 真介, 細谷 要介, 滝田 順子, 真部 淳
日本小児血液・がん学会雑誌, 53, 4, 238, 238, (一社)日本小児血液・がん学会, 2016年11月
英語

MEF2DおよびZNF384関連融合遺伝子陽性症例は小児B前駆細胞性ALLの中のサブグループを形成する(Incidence and clinical relevance of MEF2D- and ZNF384-related fusion genes in childhood B-cell precursor acute lymphoblastic leukemia: TCCSG L0416/0616 study)
大木 健太郎, 平林 真介, 加藤 元博, 中林 一彦, 秦 健一郎, 梶原 良介, 高橋 浩之, 福島 敬, 康 勝好, 真部 淳, 小原 明, 清河 信敬
日本小児血液・がん学会雑誌, 53, 4, 259, 259, (一社)日本小児血液・がん学会, 2016年11月
英語

小児再発急性リンパ性白血病患者に対するボルテゾミブ併用多剤化学療法の安全性を検討する第I相試験(Phase I Study of Bortezomib-Containing Multiagent Chemotherapy in Children with Relapsed Acute Lymphoblastic Leukemia)
長谷川 大輔, 熊本 忠史, 齋藤 明子, 嘉田 晃子, 山下 友加, 前田 尚子, 菊田 敦, 原 純一, 真部 淳, 小川 千登世
日本小児血液・がん学会雑誌, 53, 4, 253, 253, (一社)日本小児血液・がん学会, 2016年11月
英語

本邦における小児がん患児に対する疼痛管理の現状と課題 JPLSG施設調査より
加藤 陽子, 福島 啓太郎, 新小田 雄一, 森 尚子, 大曽根 眞也, 嘉数 真理子, 佐野 弘純, 篠田 邦大, 矢野 道広, 真部 淳, 足立 壯一, 日本小児白血病リンパ腫研究グループ(JPLSG)
日本小児血液・がん学会雑誌, 53, 4, 271, 271, (一社)日本小児血液・がん学会, 2016年11月
日本語

本邦における小児緩和ケア提供体制の現状と課題 JPLSG施設調査より
森 尚子, 福島 啓太郎, 加藤 陽子, 新小田 雄一, 大曽根 眞也, 嘉数 真理子, 佐野 弘純, 篠田 邦大, 矢野 道広, 真部 淳, 足立 壯一, 日本小児白血病リンパ腫研究グループ(JPLSG)
日本小児血液・がん学会雑誌, 53, 4, 271, 271, (一社)日本小児血液・がん学会, 2016年11月
日本語

本邦における小児がん患者に対する検査・処置時の鎮静および疼痛管理の現状と課題 JPLSG施設調査より
新小田 雄一, 福島 啓太郎, 加藤 陽子, 森 尚子, 大曽根 眞也, 嘉数 真理子, 佐野 弘純, 篠田 邦大, 矢野 道広, 真部 淳, 足立 壮一, 日本小児白血病リンパ腫研究グループ(JPLSG)
日本小児血液・がん学会雑誌, 53, 4, 355, 355, (一社)日本小児血液・がん学会, 2016年11月
日本語

小児白血病における腫瘍崩壊症候群およびhyperleukocytosisに対する対応 JPLSG施設アンケート調査の結果
嘉数 真理子, 福島 啓太郎, 矢野 道広, 大曽根 眞也, 佐野 弘純, 加藤 陽子, 新小田 雄一, 篠田 邦大, 真部 淳, 足立 壯一, 日本小児白血病リンパ腫研究グループ(JPLSG)
日本小児血液・がん学会雑誌, 53, 4, 369, 369, (一社)日本小児血液・がん学会, 2016年11月
日本語

下肢痛にて発症した壊血病の1例　　　　　　　　　　　　　　　
瀬谷 恵, 半田 淳比古, 松井 俊大, 吉本 優里, 長谷川 大輔, 小澤 美和, 真部 淳, 草川 功
日本小児科学会雑誌, 120, 11, 1695, 1695, (公社)日本小児科学会, 2016年11月
日本語

当院における小児がんの晩期合併症に関する検討(Late effects in the children of cancer survivors: from the single institute experience)
齋藤 合, 吉本 優里, 細谷 要介, 平林 真介, 長谷川 大輔, 石田 也寸志, 浦山 ケビン, 小澤 美和, 細谷 亮太, 真部 淳
日本小児血液・がん学会雑誌, 53, 4, 275, 275, (一社)日本小児血液・がん学会, 2016年11月
英語

軽症血友病Aに合併した慢性特発性血小板減少症性紫斑病に対して脾臓摘出術を行った1例
瀬谷 恵, 長谷川 大輔, 平林 真介, 細谷 要介, 小澤 美和, 迫田 晃子, 松藤 凡, 真部 淳
日本小児血液・がん学会雑誌, 53, 4, 321, 321, (一社)日本小児血液・がん学会, 2016年11月
日本語

高リスク神経芽腫発症から23年後に膀胱癌を発症した一例
細谷 要介, 長谷川 大輔, 永瀬 恭子, 郡司 美千代, 小林 京子, 小澤 美和, 石田 也寸志, 鈴木 高祐, 服部 一紀, 真部 淳
日本小児血液・がん学会雑誌, 53, 4, 397, 397, (一社)日本小児血液・がん学会, 2016年11月
日本語

母子共に末期がんの家族に対するチームアプローチにおける多職種カンファレンスの意義
小口 祐子, 大川 智子, 小川 恵理子, 阿佐美 百合子, 宮本 智史, 木村 俊介, 長谷川 大輔, 小澤 美和, 真部 淳, 山本 光映
日本小児血液・がん学会雑誌, 53, 4, 444, 444, (一社)日本小児血液・がん学会, 2016年11月
日本語

小児造血器腫瘍に対する共通免疫学的診断パネルによって診断されたBilineal Leukemiaの特徴(The characteristics of Bilineal Leukemia diagnosed by nationwide immunophenotyping for pediatric hematological malignancy in Japan)
出口 隆生, 清河 信敬, 大木 健太郎, 橋井 佳子, 真部 淳, 足立 壯一, 齋藤 明子, 堀部 敬三, 駒田 美弘
日本小児血液・がん学会雑誌, 53, 4, 280, 280, (一社)日本小児血液・がん学会, 2016年11月
英語

本邦において2002年から2011年までに発生した2例の小児BCL2およびMYC dual-hit白血病(Two cases of pediatric BCL2 and MYC dual-hit leukemia between 2002 and 2011 in Japan)
坂口 公祥, 今村 俊彦, 石丸 紗恵, 今井 千速, 下之段 秀美, 岡田 恵子, 出口 隆生, 橋井 佳子, 清河 信敬, 齋藤 明子, 真部 淳, 佐藤 篤, 康 勝好
日本小児血液・がん学会雑誌, 53, 4, 370, 370, (一社)日本小児血液・がん学会, 2016年11月
英語

小児再生不良性貧血および骨髄異形成症候群の形態中央診断 1500例のまとめ(Central morphology review of aplastic anemia and myelodysplastic syndrome in children: the summary of 1,500 cases)
濱 麻人, 真部 淳, 長谷川 大輔, 野沢 和江, 成田 敦, 村松 秀城, 高橋 義行, 渡邉 健一郎, 小原 明, 伊藤 雅文, 小島 勢二
日本小児血液・がん学会雑誌, 53, 4, 233, 233, (一社)日本小児血液・がん学会, 2016年11月, ［査読有り］
英語

本邦における治療関連性急性白血病および悪性リンパ腫の全国調査結果について(Nation-wide survey of therapy related leukemia and lymphoma in Japan)
今村 俊彦, 多賀 崇, 高木 正稔, 河崎 裕英, 康 勝好, 滝 智彦, 足立 壮一, 真部 淳, 石田 也寸志, 日本小児血液・がん学会白血病リンパ腫委員会
日本小児血液・がん学会雑誌, 53, 4, 275, 275, (一社)日本小児血液・がん学会, 2016年11月, ［査読有り］
英語

Cervical ultrasound and computed tomography of Kawasaki disease: Comparison with lymphadenitis
Taiki Nozaki, Yuka Morita, Daisuke Hasegawa, Akari Makidono, Yuri Yoshimoto, Jay Starkey, Isao Kusakawa, Atsushi Manabe, Yukihisa Saida
PEDIATRICS INTERNATIONAL, 58, 11, 1146, 1152, WILEY-BLACKWELL, 2016年11月, ［査読有り］
英語, 研究論文（学術雑誌）, BackgroundDifferentiating Kawasaki disease (KD) from cervical lymphadenitis (CL) is clinically difficult but essential given that treatment and outcome differ significantly. Research on differentiation between KD and CL using ultrasound (US) and computed tomography (CT) is limited. The purpose of this study was to identify cervical US and CT findings that may differentiate KD from CL.
MethodsWe retrospectively reviewed cervical US of 25 KD patients and 25 CL patients, and CT of 14 KD patients, and 14 CL patients. Two radiologists analyzed specific imaging features on US (lymph node size, shape, echogenicity, margins, laterality, necrosis, and presence of normal hilum) and on CT (size and location of enlarged nodes, laterality, perinodal infiltration, and retropharyngeal edema).
ResultsOn US, patients with KD more frequently had lymph nodes with a cluster of grapes appearance (KD vs CL: 64% vs 32%, P < 0.05) and less frequently had poorly circumscribed margins (0% vs 36%, P < 0.01), necrosis (0% vs 32%, P < 0.01), or non-visualization of the hilum (4% vs 36%, P < 0.01). On CT, KD patients more frequently had retropharyngeal edema (100% vs 29%, P < 0.001) and less frequently had level 4 lymphadenopathy (14% vs 79%, P < 0.01) than CL patients.
ConclusionsUltrasound is mainly useful for excluding purulent lymphadenopathy while CT is a useful diagnostic tool for differentiating KD from CL, especially in patients with incomplete KD, who present with prominent cervical lymphadenopathy and other equivocal principal findings.

Cervical ultrasound and computed tomography of Kawasaki disease: Comparison with lymphadenitis
Taiki Nozaki, Yuka Morita, Daisuke Hasegawa, Akari Makidono, Yuri Yoshimoto, Jay Starkey, Isao Kusakawa, Atsushi Manabe, Yukihisa Saida
Pediatrics International, 58, 11, 1146, 1152, Blackwell Publishing, 2016年11月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Differentiating Kawasaki disease (KD) from cervical lymphadenitis (CL) is clinically difficult but essential given that treatment and outcome differ significantly. Research on differentiation between KD and CL using ultrasound (US) and computed tomography (CT) is limited. The purpose of this study was to identify cervical US and CT findings that may differentiate KD from CL. Methods: We retrospectively reviewed cervical US of 25 KD patients and 25 CL patients, and CT of 14 KD patients, and 14 CL patients. Two radiologists analyzed specific imaging features on US (lymph node size, shape, echogenicity, margins, laterality, necrosis, and presence of normal hilum) and on CT (size and location of enlarged nodes, laterality, perinodal infiltration, and retropharyngeal edema). Results: On US, patients with KD more frequently had lymph nodes with a “cluster of grapes” appearance (KD vs CL: 64% vs 32%, P <
0.05) and less frequently had poorly circumscribed margins (0% vs 36%, P <
0.01), necrosis (0% vs 32%, P <
0.01), or non-visualization of the hilum (4% vs 36%, P <
0.01). On CT, KD patients more frequently had retropharyngeal edema (100% vs 29%, P <
0.001) and less frequently had level 4 lymphadenopathy (14% vs 79%, P <
0.01) than CL patients. Conclusions: Ultrasound is mainly useful for excluding purulent lymphadenopathy while CT is a useful diagnostic tool for differentiating KD from CL, especially in patients with incomplete KD, who present with prominent cervical lymphadenopathy and other equivocal principal findings.

本邦におけるt(8;14)(q24;q32)再構成を伴う小児の前駆B細胞性急性リンパ芽球性白血病(Pediatric B cell precursor acute lymphoblastic leukemia with t(8;14)(q24;q32) rearrangement in Japan)　　　　　　　　　　　　　　　
Sakaguchi Kimiyoshi, Imamura Toshihiko, Ishimaru Sae, Imai Chihaya, Shimonodan Hidemi, Hamamoto Kazuko, Okada Keiko, Taketani Takeshi, Kanai Rie, Kato Motohiro, Kojima Yasuko, Watanabe Arata, Deguchi Takao, Hashii Yoshiko, Kiyokawa Nobutaka, Saito-Moriya Akiko, Manabe Atsushi, Sato Atsushi, Koh Katsuyoshi
臨床血液, 57, 9, 1503, 1503, (一社)日本血液学会-東京事務局, 2016年09月
英語

脳動静脈奇形(AVM)の出血に対し血管内塞栓術とAVM摘出術を施行した2ヵ月女児例　　　　　　　　　　　　　　　
後藤 耕策, 吉本 優里, 角谷 和歌子, 松井 俊大, 秋山 類, 藤井 本晴, 小澤 美和, 真部 淳, 新見 康成, 草川 功
日本小児科学会雑誌, 120, 9, 1393, 1393, (公社)日本小児科学会, 2016年09月
日本語

Ewing sarcoma/primitive neuroectodermal tumor of the kidney treated with chemotherapy including ifosfamide
Hiroki Yoshihara, Takahiro Kamiya, Yosuke Hosoya, Daisuke Hasegawa, Chitose Ogawa, Hiroshi Asanuma, Ryuichi Mizuno, Ryota Hosoya, Atsushi Manabe
PEDIATRICS INTERNATIONAL, 58, 8, 766, 769, WILEY-BLACKWELL, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the kidney is extremely rare, and is usually diagnosed after nephrectomy without neoadjuvant chemotherapy. Although ifosfamide and etoposide improve survival to a great extent in ES/PNET, the use of nephrotoxic agent, particularly ifosfamide, is a concern after nephrectomy. We describe the case of a 14-year-old female patient with abdominal mass who was diagnosed with ES/PNET of the right kidney after nephrectomy. Adjuvant chemotherapy including ifosfamide and etoposide were given. The estimated glomerular filtration rate decreased to 75% after the end of therapy. There was no evidence of recurrence 70 months after initial diagnosis.

Ewing sarcoma/primitive neuroectodermal tumor of the kidney treated with chemotherapy including ifosfamide
Hiroki Yoshihara, Takahiro Kamiya, Yosuke Hosoya, Daisuke Hasegawa, Chitose Ogawa, Hiroshi Asanuma, Ryuichi Mizuno, Ryota Hosoya, Atsushi Manabe
Pediatrics International, 58, 8, 766, 769, Blackwell Publishing, 2016年08月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the kidney is extremely rare, and is usually diagnosed after nephrectomy without neoadjuvant chemotherapy. Although ifosfamide and etoposide improve survival to a great extent in ES/PNET, the use of nephrotoxic agent, particularly ifosfamide, is a concern after nephrectomy. We describe the case of a 14-year-old female patient with abdominal mass who was diagnosed with ES/PNET of the right kidney after nephrectomy. Adjuvant chemotherapy including ifosfamide and etoposide were given. The estimated glomerular filtration rate decreased to 75% after the end of therapy. There was no evidence of recurrence 70 months after initial diagnosis.

Overview.
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 57, 7, 881, 2016年07月, ［査読有り］

治療方針に難渋したIgA血管炎に伴う腸重積の1例　　　　　　　　　　　　　　　
栗山 絢子, 真部 淳, 瀬谷 恵, 松井 俊大, 右田 美里, 迫田 晃子, 草川 功, 松藤 凡
日本小児救急医学会雑誌, 15, 2, 260, 260, (一社)日本小児救急医学会, 2016年06月
日本語

Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan
Yasushi Ishida, Dongmei Qiu, Miho Maeda, Junichiro Fujimoto, Hisato Kigasawa, Ryoji Kobayashi, Maho Sato, Jun Okamura, Shinji Yoshinaga, Takeshi Rikiishi, Hiroyuki Shichino, Chikako Kiyotani, Kazuko Kudo, Keiko Asami, Hiroki Hori, Hiroshi Kawaguchi, Hiroko Inada, Souichi Adachi, Atsushi Manabe, Tatsuo Kuroda
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 21, 3, 506, 516, SPRINGER JAPAN KK, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan.
A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis.
One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9-1.4) at 10 years and 2.6 % (95 % CI 2.1-3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-year survivors (n = 5,387), confirmed these low incidence rates. The SIR of secondary cancers was 12.1 (95 % CI 10.1-14.4). In the Cox analysis, the hazard ratios for secondary cancers were 3.81 (95 % CI 1.53-9.47) for retinoblastoma, 2.78 (95 % CI 1.44-5.38) for bone/soft tissue sarcomas, and 1.81 (95 % CI 1.16-2.83) for allogeneic stem cell transplantation.
The cumulative incidence of secondary cancers in children in Japan was not high; however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers.

Severe 6-mercaptopurine-induced hematotoxicity in childhood an ALL patient with homozygous NUDT15 missence variants.
Shunsuke Kimura, Daisuke Hasegawa, Yuri Yoshimoto, Shinsuke Hirabayashi, Yosuke Hosoya, Hiroki Yoshihara, Tadashi Kumamoto, Yoichi Tanaka, Atsushi Manabe
[Rinsho ketsueki] The Japanese journal of clinical hematology, 57, 6, 748, 53, 一般社団法人 日本血液学会, 2016年06月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, Thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) variants are considered to be genes responsible for severe myelotoxicity induced by 6-mercaptopurine (6MP). We report a 4-year-old girl with acute lymphoblastic leukemia, who developed the complication of severe 6MP-induced myelotoxicity due to homozygous NUDT15 variant alleles. In early consolidation therapy containing 6MP, her course was complicated by severe neutropenia (Grade 4) and chemotherapy had to be discontinued for 33 days. The 6MP dose was subsequently adjusted based on the white blood cell count. The ratios of the prescribed 6MP dose over the protocol dose in early consolidation, central nervous system (CNS) prophylaxis, re-induction, interim maintenance and maintenance therapy were 63%, 27%, 4%, 26% and 7%, respectively. Suspension of therapy was required during early consolidation, CNS prophylaxis and interim maintenance therapy. We investigated candidate genes for 6MP-associated myelotoxicity and found homozygous NUDT15 variant alleles and a heterozygous inosine triphosphate pyrophosphatase (ITPA) variant allele. In patients with homozygous NUDT15 variants, drastic reduction (less than 10%) of the 6MP dose from the protocol dose might be required not only during maintenance therapy, but also during other treatment courses containing 6MP. Screening of candidate genes at diagnosis is recommended in order to avoid serious adverse events.

Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan
Yasushi Ishida, Dongmei Qiu, Miho Maeda, Junichiro Fujimoto, Hisato Kigasawa, Ryoji Kobayashi, Maho Sato, Jun Okamura, Shinji Yoshinaga, Takeshi Rikiishi, Hiroyuki Shichino, Chikako Kiyotani, Kazuko Kudo, Keiko Asami, Hiroki Hori, Hiroshi Kawaguchi, Hiroko Inada, Souichi Adachi, Atsushi Manabe, Tatsuo Kuroda
International Journal of Clinical Oncology, 21, 3, 506, 516, Springer Tokyo, 2016年06月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan. Methods: A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis. Results: One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9–1.4) at 10 years and 2.6 % (95 % CI 2.1–3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-year survivors (n = 5,387), confirmed these low incidence rates. The SIR of secondary cancers was 12.1 (95 % CI 10.1–14.4). In the Cox analysis, the hazard ratios for secondary cancers were 3.81 (95 % CI 1.53–9.47) for retinoblastoma, 2.78 (95 % CI 1.44–5.38) for bone/soft tissue sarcomas, and 1.81 (95 % CI 1.16–2.83) for allogeneic stem cell transplantation. Conclusions: The cumulative incidence of secondary cancers in children in Japan was not high
however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers.

先天性QT延長症候群と局在関連てんかんを合併したKCNQ1変異を認める女児例
代田 惇朗, 小野 林太郎, 荻原 正明, 平林 真介, 横山 美奈, 白井 丈晶, 小澤 美和, 草川 功, 真部 淳
脳と発達, 48, Suppl., S369, (一社)日本小児神経学会, 2016年05月

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan
T. Imamura, N. Kiyokawa, M. Kato, C. Imai, Y. Okamoto, M. Yano, K. Ohki, Y. Yamashita, Y. Kodama, A. Saito, M. Mori, S. Ishimaru, T. Deguchi, Y. Hashii, Y. Shimomura, T. Hori, K. Kato, H. Goto, C. Ogawa, K. Koh, T. Taki, A. Manabe, A. Sato, A. Kikuta, S. Adachi, K. Horibe, A. Ohara, A. Watanabe, Y. Kawano, E. Ishii, H. Shimada
BLOOD CANCER JOURNAL, 6, NATURE PUBLISHING GROUP, 2016年05月
英語, 研究論文（学術雑誌）, Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/mu l) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6 +/- 9.7% and 73.5 +/- 8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.

A Cytokine-Based Diagnostic Program in Pediatric Aplastic Anemia and Hypocellular Refractory Cytopenia of Childhood
Shaimaa Elmahdi, Asahito Hama, Atsushi Manabe, Daisuke Hasegawa, Hideki Muramatsu, Atsushi Narita, Nobuhiru Nishio, Olfat Ismael, Nozomu Kawashima, Yusuke Okuno, Yinyan Xu, Xinan Wang, Yoshiyuki Takahashi, Masafumi Ito, Seiji Kojima
PEDIATRIC BLOOD & CANCER, 63, 4, 652, 658, WILEY-BLACKWELL, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, BackgroundDistinguishing hypocellular refractory cytopenia of childhood (RCC) from aplastic anemia (AA) is challenging. Thus far, no studies have compared the cytokine profiles in patients with AA to those with hypocellular RCC. In the present study, we addressed whether thrombopoietin (TPO) and interleukin 17 (IL-17) plasma levels are useful for differentiating between the two diseases.
MethodsWe measured the endogenous plasma concentrations of TPO and IL-17 in 29 patients with AA, 34 patients with hypocellular RCC, and 31 healthy controls using sensitive enzyme-linked immunosorbent assays.
ResultsThe TPO and IL-17 plasma levels were significantly lower in patients with hypocellular RCC than in patients with AA (P < 0.001 and P = 0.007, respectively). The multivariate logistic regression analysis identified moderate disease severity, TPO levels of <1,369.8 pg/ml (TPO-low group, n = 32; odds ratio (OR), 13.40; 95% confidence intervals (CI), 3.001-51.254; P < 0.001), and IL-17 levels of <22.2 pg/ml (IL-17-low group, n = 33; OR, 4.11; 95% CI, 1.03319.404; P = 0.031) as independent factors discriminating hypocellular RCC from AA. Importantly, 25 (78.1%) of 32 patients in the TPO-low group and 25 (75.8%) of 33 patients in the IL-17-low group were diagnosed as having hypocellular RCC. Moreover, 22 (71%) of 31 patients in the TPO-high group and 21 (70%) of 30 patients in the IL-17-high group were diagnosed as having AA.
ConclusionsTPO and IL-17 levels are useful for differentiating hypocellular RCC from AA. Prospective studies are required to confirm our findings.

Residual disease detected by multidimensional flow cytometry shows prognostic significance in childhood acute myeloid leukemia with intermediate cytogenetics and negative FLT3-ITD: a report from the Tokyo Children's Cancer Study Group
Dai Keino, Akitoshi Kinoshita, Daisuke Tomizawa, Hiroyuki Takahashi, Kohmei Ida, Hidemitsu Kurosawa, Kazutoshi Koike, Setsuo Ota, Noriyuki Iwasaki, Junya Fujimura, Yuki Yuza, Chikako Kiyotani, Shohei Yamamoto, Tomoo Osumi, Takahiro Ueda, Shinji Mochizuki, Keiichi Isoyama, Ryoji Hanada, Akio Tawa, Atsushi Manabe, Yoichi Toguchi, Akira Ohara
INTERNATIONAL JOURNAL OF HEMATOLOGY, 103, 4, 416, 422, SPRINGER JAPAN KK, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Residual disease (RD) after induction chemotherapy may predict clinical outcome in acute myeloid leukemia (AML). In the present study, we investigated the prognostic significance of RD detected by multidimensional flow cytometry (MDF) among 34 children treated for AML in a clinical trial (JPLSG AML-05) in Japan. Bone marrow samples were analyzed at the points of the end of the first induction course (BMA-1) and second induction course (BMA-2) by MDF. RD was evaluated by detecting the immature cells showing abnormal antigen expression pattern; CD34(+), CD15(+), CD7(+). Thirteen (39.4 %) of 34 patients at BMA-1 and 8 (27.6 %) of 34 at BMA-2 had RD levels >= 0.1 %. There was no significant difference in 3y-EFS and 3y-OS between patients with RD levels >= 0.1 % and those with RD levels <0.1 % (53.8 versus 70.0 %, P = 0.30 and 50.0 versus 66.7 %, P = 0.27, respectively). However, IR cytogenetics and negative FLT3-ITD patients with RD levels >= 0.1 % exhibited significantly lower 3y-EFS and 3y-OS than those with RD levels <0.1 % (33.3 versus 83.3 %, P = 0.02 and 20.0 versus 76.9 %, P = 0.005, respectively). Our study suggests that RD shows prognostic relevance in pediatric patients with IR cytogenetics and negative FLT3-ITD AML.

NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity
Takaya Moriyama, Rina Nishii, Virginia Perez-Andreu, Wenjian Yang, Federico Antillon Klussmann, Xujie Zhao, Ting-Nien Lin, Keito Hoshitsuki, Jacob Nersting, Kentaro Kihira, Ute Hofmann, Yoshihiro Komada, Motohiro Kato, Robert McCorkle, Lie Li, Katsuyoshi Koh, Cesar Rolando Najera, Shirley Kow-Yin Kham, Tomoya Isobe, Zhiwei Chen, Edwynn Kean-Hui Chiew, Deepa Bhojwani, Cynthia Jeffries, Yan Lu, Matthias Schwab, Hiroto Inaba, Ching-Hon Pui, Mary V. Relling, Atsushi Manabe, Hiroki Hori, Kjeld Schmiegelow, Allen E. J. Yeoh, William E. Evans, Jun J. Yang
NATURE GENETICS, 48, 4, 367, +, NATURE PUBLISHING GROUP, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Widely used as anticancer and immunosuppressive agents, thiopurines have narrow therapeutic indices owing to frequent toxicities, partly explained by TPMT genetic polymorphisms. Recent studies identified germline NUDT15 variation as another critical determinant of thiopurine intolerance, but the underlying molecular mechanisms and the clinical implications of this pharmacogenetic association remain unknown. In 270 children enrolled in clinical trials for acute lymphoblastic leukemia in Guatemala, Singapore and Japan, we identified four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile and p.Val18_Val19insGlyVal) that resulted in 74.4-100% loss of nucleotide diphosphatase activity. Loss-of-function NUDT15 diplotypes were consistently associated with thiopurine intolerance across the three cohorts (P = 0.021, 2.1 x 10(-5) and 0.0054, respectively; meta-analysis P = 4.45 x 10(-8), allelic effect size = -11.5). Mechanistically, NUDT15 inactivated thiopurine metabolites and decreased thiopurine cytotoxicity in vitro, and patients with defective NUDT15 alleles showed excessive levels of thiopurine active metabolites and toxicity. Taken together, these results indicate that a comprehensive pharmacogenetic model integrating NUDT15 variants may inform personalized thiopurine therapy.

Guest Editorial: Inherited bone marrow failure and myelodysplasia in children: how much do we know about pediatric diseases?
Atsushi Manabe
International Journal of Hematology, 103, 4, 359, Springer Tokyo, 2016年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Residual disease detected by multidimensional flow cytometry shows prognostic significance in childhood acute myeloid leukemia with intermediate cytogenetics and negative FLT3-ITD: a report from the Tokyo Children's Cancer Study Group.
Dai Keino, Akitoshi Kinoshita, Daisuke Tomizawa, Hiroyuki Takahashi, Kohmei Ida, Hidemitsu Kurosawa, Kazutoshi Koike, Setsuo Ota, Noriyuki Iwasaki, Junya Fujimura, Yuki Yuza, Chikako Kiyotani, Shohei Yamamoto, Tomoo Osumi, Takahiro Ueda, Shinji Mochizuki, Keiichi Isoyama, Ryoji Hanada, Akio Tawa, Atsushi Manabe, Yoichi Toguchi, Akira Ohara
International journal of hematology, 103, 4, 416, 22, 2016年04月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Residual disease (RD) after induction chemotherapy may predict clinical outcome in acute myeloid leukemia (AML). In the present study, we investigated the prognostic significance of RD detected by multidimensional flow cytometry (MDF) among 34 children treated for AML in a clinical trial (JPLSG AML-05) in Japan. Bone marrow samples were analyzed at the points of the end of the first induction course (BMA-1) and second induction course (BMA-2) by MDF. RD was evaluated by detecting the immature cells showing abnormal antigen expression pattern; CD34(+), CD15(+), CD7(+). Thirteen (39.4 %) of 34 patients at BMA-1 and 8 (27.6 %) of 34 at BMA-2 had RD levels ≥0.1 %. There was no significant difference in 3y-EFS and 3y-OS between patients with RD levels ≥0.1 % and those with RD levels <0.1 % (53.8 versus 70.0 %, P = 0.30 and 50.0 versus 66.7 %, P = 0.27, respectively). However, IR cytogenetics and negative FLT3-ITD patients with RD levels ≥0.1 % exhibited significantly lower 3y-EFS and 3y-OS than those with RD levels <0.1 % (33.3 versus 83.3 %, P = 0.02 and 20.0 versus 76.9 %, P = 0.005, respectively). Our study suggests that RD shows prognostic relevance in pediatric patients with IR cytogenetics and negative FLT3-ITD AML.

A Cytokine-Based Diagnostic Program in Pediatric Aplastic Anemia and Hypocellular Refractory Cytopenia of Childhood
Shaimaa Elmahdi, Asahito Hama, Atsushi Manabe, Daisuke Hasegawa, Hideki Muramatsu, Atsushi Narita, Nobuhiru Nishio, Olfat Ismael, Nozomu Kawashima, Yusuke Okuno, Yinyan Xu, Xinan Wang, Yoshiyuki Takahashi, Masafumi Ito, Seiji Kojima
Pediatric Blood and Cancer, 63, 4, 652, 658, John Wiley and Sons Inc., 2016年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Distinguishing hypocellular refractory cytopenia of childhood (RCC) from aplastic anemia (AA) is challenging. Thus far, no studies have compared the cytokine profiles in patients with AA to those with hypocellular RCC. In the present study, we addressed whether thrombopoietin (TPO) and interleukin 17 (IL-17) plasma levels are useful for differentiating between the two diseases. Methods: We measured the endogenous plasma concentrations of TPO and IL-17 in 29 patients with AA, 34 patients with hypocellular RCC, and 31 healthy controls using sensitive enzyme-linked immunosorbent assays. Results: The TPO and IL-17 plasma levels were significantly lower in patients with hypocellular RCC than in patients with AA (P <
0.001 and P = 0.007, respectively). The multivariate logistic regression analysis identified moderate disease severity, TPO levels of <
1,369.8 pg/ml (TPO-low group, n = 32
odds ratio (OR), 13.40
95% confidence intervals (CI), 3.001-51.254
P <
0.001), and IL-17 levels of <
22.2 pg/ml (IL-17-low group, n = 33
OR, 4.11
95% CI, 1.033-19.404
P = 0.031) as independent factors discriminating hypocellular RCC from AA. Importantly, 25 (78.1%) of 32 patients in the TPO-low group and 25 (75.8%) of 33 patients in the IL-17-low group were diagnosed as having hypocellular RCC. Moreover, 22 (71%) of 31 patients in the TPO-high group and 21 (70%) of 30 patients in the IL-17-high group were diagnosed as having AA. Conclusions: TPO and IL-17 levels are useful for differentiating hypocellular RCC from AA. Prospective studies are required to confirm our findings.

【小児慢性疾患の成人期移行の現状と問題点】 悪性新生物 血液腫瘍(白血病、悪性リンパ腫)
吉本 優里, 真部 淳
小児科臨床, 69, 4, 549, (株)日本小児医事出版社, 2016年04月

NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity
Takaya Moriyama, Rina Nishii, Virginia Perez-Andreu, Wenjian Yang, Federico Antillon Klussmann, Xujie Zhao, Ting-Nien Lin, Keito Hoshitsuki, Jacob Nersting, Kentaro Kihira, Ute Hofmann, Yoshihiro Komada, Motohiro Kato, Robert McCorkle, Lie Li, Katsuyoshi Koh, Cesar Rolando Najera, Shirley Kow-Yin Kham, Tomoya Isobe, Zhiwei Chen, Edwynn Kean-Hui Chiew, Deepa Bhojwani, Cynthia Jeffries, Yan Lu, Matthias Schwab, Hiroto Inaba, Ching-Hon Pui, Mary V Relling, Atsushi Manabe, Hiroki Hori, Kjeld Schmiegelow, Allen E.J. Yeoh, William E Evans, Jun J. Yang
Nature Genetics, 48, 4, 367, 373, Nature Publishing Group, 2016年03月29日, ［査読有り］
英語, 研究論文（学術雑誌）, Widely used as anticancer and immunosuppressive agents, thiopurines have narrow therapeutic indices owing to frequent toxicities, partly explained by TPMT genetic polymorphisms. Recent studies identified germline NUDT15 variation as another critical determinant of thiopurine intolerance, but the underlying molecular mechanisms and the clinical implications of this pharmacogenetic association remain unknown. In 270 children enrolled in clinical trials for acute lymphoblastic leukemia in Guatemala, Singapore and Japan, we identified four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile and p.Val18-Val19insGlyVal) that resulted in 74.4-100% loss of nucleotide diphosphatase activity. Loss-of-function NUDT15 diplotypes were consistently associated with thiopurine intolerance across the three cohorts (P = 0.021, 2.1 × 10 -5 and 0.0054, respectively
meta-analysis P = 4.45 × 10 -8, allelic effect size = -11.5). Mechanistically, NUDT15 inactivated thiopurine metabolites and decreased thiopurine cytotoxicity in vitro, and patients with defective NUDT15 alleles showed excessive levels of thiopurine active metabolites and toxicity. Taken together, these results indicate that a comprehensive pharmacogenetic model integrating NUDT15 variants may inform personalized thiopurine therapy.

小児T細胞性ALLにおける既知遺伝子異常の解析 TCCSG-ALL研究　　　　　　　　　　　　　　　
大木 健太郎, 清河 信敬, 朴 明子, 小林 健一郎, 福島 敬, 康 勝好, 花田 良二, 林 泰秀, 真部 淳, 小原 明, 東京小児がん研究グループ
日本小児科学会雑誌, 120, 2, 259, 259, (公社)日本小児科学会, 2016年02月
日本語

小児急性リンパ性白血病の維持療法期間におけるメルカプトプリン及びメトトレキサート投与量の推移 単施設における検討
歌野 智之, 田中 庸一, 木津 純子, 神谷 尚宏, 小川 千登世, 石田 也寸志, 細谷 亮太, 真部 淳
日本小児血液・がん学会雑誌, 52, 5, 399, 404, (NPO)日本小児血液・がん学会, 2016年02月
日本語, 【背景】メルカプトプリン(6-MP)及びメトトレキサート(MTX)の臨床効果や副作用は個体差が大きく、個々によって至適投与量は大きく異なる事が知られている。本研究は、両薬剤の投与量推移を調査し、患者背景及び再発との関連性について調査した。【方法】1995年4月〜2010年3月の期間に当施設で急性リンパ性白血病(ALL)と診断され、維持療法が終了した患児を対象とした。両薬剤の投与量推移を調査し、投与量推移別に患者背景(性別、診断時:白血球数、年齢、immunophenotype、維持療法開始時:体表面積、Prednisolone反応性、リスク分類、肥満度)を比較した。また、再発患者と非再発患者の6-MP及びMTXの投与量推移を比較した。【結果】維持療法開始1年以内に6-MP投与量の変更を要した患児は50名中34名(増量20名、減量14名)、MTX投与量の変更を要した患児は50名中18名(増量

自閉症スペクトラム障害のフォロー中に発作時脳波での鑑別を要した前頭葉てんかん
角谷 和歌子, 代田 惇朗, 松井 俊大, 田中 育子, 横山 美奈, 長谷川 大輔, 小澤 美和, 荻原 正明, 草川 功, 真部 淳
日本小児科学会雑誌, 120, 2, 516, (公社)日本小児科学会, 2016年02月

水痘感染の既往のない非血縁者間臍帯血移植後男児に生じた帯状疱疹
木村 俊介, 長谷川 大輔, 代田 惇朗, 松井 俊大, 吉本 優里, 平林 真介, 細谷 要介, 熊本 忠志, 真部 淳
日本小児科学会雑誌, 120, 2, 501, (公社)日本小児科学会, 2016年02月

症例報告の書き方、査読の仕方 論文査読のしかた
真部 淳
日本小児科学会雑誌, 120, 2, 210, (公社)日本小児科学会, 2016年02月

From a paper-based to a web-based Journal
Atsushi Manabe
PEDIATRICS INTERNATIONAL, 58, 1, 3, 3, WILEY-BLACKWELL, 2016年01月, ［査読有り］
英語

ZNF384-related fusion genes consist of a subgroup with a characteristic immunophenotype in childhood B-cell precursor acute lymphoblastic leukemia.
Hirabayashi Shinsuke, Ohki Kentaro, Nakabayashi Kazuhiko, Ichikawa Hitoshi, Momozawa Yukihide, Okamura Kohji, Yaguchi Akinori, Terada Kazuki, Saito Yuya, Yoshimi Ai, Ogata-Kawata Hiroko, Sakamoto Hiromi, Kato Motohiro, Fujimura Junya, Hino Moeko, Kinoshita Akitoshi, Kakuda Hiromi, Kurosawa Hidemitsu, Kato Keisuke, Kajiwara Ryosuke, Moriwaki Koichi, Morimoto Tsuyoshi, Nakamura Kozue, Noguchi Yasushi, Osumi Tomoo, Sakashita Kazuo, Takita Junko, Yuza Yuki, Matsuda Koich, Yoshida Teruhiko, Matsumoto Kenji, Hata Kenichiro, Kubo Michiaki, Matsubara Yoichi, Fukushima Takashi, Koh Katsuyoshi, Manabe Atsushi, Ohara Akira, Kiyokawa Nobutaka
ZNF384-related fusion genes consist of a subgroup with a characteristic immunophenotype in childhood B-cell precursor acute lymphoblastic leukemia., 2016年
:Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 6 fusion partners have reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or PCR. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including EP300-ZNF384 that we reported recently, the to

メチルプレドニゾロン・パルス療法とタクロリムスによる治療が奏効した抗MDA5抗体陽性の若年性皮膚筋炎の女児例
山口 賢一, 横田 俊平, 代田 惇朗, 小澤 美和, 真部 淳, 草川 功
日本小児科学会雑誌, 120, 1, 96, (公社)日本小児科学会, 2016年01月

小児最重症再生不良性貧血に対する非血縁者間臍帯血移植
木村 俊介, 長谷川 大輔, 松井 俊大, 代田 惇朗, 石田 悠志, 吉本 優里, 平林 真介, 細谷 要介, 吉原 宏樹, 熊本 忠史, 森 愼一郎, 真部 淳
日本小児血液・がん学会雑誌, 53, 1, 21, 25, 日本小児血液・がん学会, 2016年
日本語, 最重症再生不良性貧血の治療として，重症感染症などにより早期の移植が必要にも関わらずHLA適合ドナーが得られない場合，非血縁者間臍帯血移植やHLA不適合血縁者間移植が選択肢となる．しかし，このような代替ドナーからの移植では，移植片対宿主病や生着不全の危険が高いことが問題である．我々は，感染を反復する最重症再生不良性貧血の2歳男児に対して，HLA 5/6抗原一致非血縁者間臍帯血移植を行った．総有核細胞数とCD34陽性細胞数の豊富な臍帯血を用いるとともに，前処置に低線量放射線照射を併用した．また，移植前に鉄キレート療法を行った．移植後day 20に生着が得られ，重篤な急性移植片対宿主病は認めなかった．前処置に用いた抗胸腺グロブリンの影響も疑われるサイトメガロウイルス抗原血症が5か月遷延したが，非血縁者間臍帯血移植は最重症再生不良性貧血の治療選択肢のひとつとなりうると考えられた．

A novel recurrent EP300-ZNF384 gene fusion in B-cell precursor acute lymphoblastic leukemia
Y. Gocho, N. Kiyokawa, H. Ichikawa, K. Nakabayashi, T. Osumi, T. Ishibashi, H. Ueno, K. Terada, K. Oboki, H. Sakamoto, Y. Shioda, M. Imai, Y. Noguchi, Y. Arakawa, Y. Kojima, D. Toyama, K. Hata, T. Yoshida, K. Matsumoto, M. Kato, T. Fukushima, K. Koh, A. Manabe, A. Ohara
Leukemia, 29, 12, 2445, 2448, Nature Publishing Group, 2015年12月01日
英語

英語論文の書き方
真部 淳
日本小児科学会雑誌, 119, 12, 1728, (公社)日本小児科学会, 2015年12月

【小児血液・腫瘍性疾患の診断と治療のトピックス】 診断のトピックス 白血病とGWAS(genome-wide association study)
真部 淳
小児科診療, 78, 12, 1753, (株)診断と治療社, 2015年12月
様々な疾患において宿主(患者)の生殖細胞系列の遺伝子変異を網羅的に検索するgenome-wide association study(GWAS:ゲノムワイド関連解析)が行われている。小児の急性リンパ性白血病(acute lymphoblastic leukemia:ALL)ではGWASにより、ALLのなりやすさと関連するARID5Bなどの遺伝子多型ならびに薬物の毒性と関連するNUDT15などの遺伝子多型がわかってきた。近い将来の臨床応用が期待される。(著者抄録)

Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.
Tomizawa D, Kato M, Takahashi H, Fujimura J, Inukai T, Fukushima T, Kiyokawa N, Koh K, Manabe A, Ohara A
International journal of hematology, 102, 5, 602, 610, 2015年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

融合遺伝子TCF3-ZNF384陽性B前駆細胞性急性リンパ芽球性白血病5例の臨床的特徴(Clinical characteristics of five cases of B-cell precursor acute lymphoblastic leukemia with TCF3-ZNF384 fusion gene)
平林 真介, 大木 健太郎, 清河 信敬, 谷口 明徳, 寺田 和樹, 市川 仁, 中林 一彦, 秦 健一郎, 松田 浩一, 桃沢 幸秀, 久保 充明, 松原 洋一, 福島 敬, 康 勝好, 真部 淳, 小原 明
日本小児血液・がん学会雑誌, 52, 4, 260, 260, (一社)日本小児血液・がん学会, 2015年10月
英語

小児T-ALLにおける6qLOHの頻度と予後解析 TCCSG ALL L0416/L0616(Frequency and prognostic impact of loss of heterozygosity at chromosome 6q in pediatric acute T-cell lymphoblastic leukemia: TCCSG ALL-L0416/L0616 Trial)
大木 健太郎, 清河 信敬, 朴 明子, 小林 健一郎, 福島 敬, 康 勝好, 土田 昌宏, 林 泰秀, 真部 淳, 小原 明
日本小児血液・がん学会雑誌, 52, 4, 267, 267, (一社)日本小児血液・がん学会, 2015年10月
英語

小児B前駆細胞性急性リンパ芽球性白血病における、PAX5の新規融合遺伝子CBFA2T2の同定(Identification of CBFA2T2 as a novel PAX5 fusion partner gene in pediatric B-precursor acute lymphoblastic leukemia)
寺田 和樹, 清河 信敬, 大木 健太郎, 木川 崇, 櫻井 彩子, 五十嵐 俊二, 谷口 明徳, 石橋 武士, 中林 一彦, 市川 仁, 松本 健治, 福島 敬, 康 勝好, 真部 淳, 小原 明, 角南 勝介
日本小児血液・がん学会雑誌, 52, 4, 349, 349, (一社)日本小児血液・がん学会, 2015年10月
英語

TCCSG施設ならびにTCCSG医師における小児がん晩期合併症の経験に関する調査
清谷 知賀子, 前田 美穂, 青木 由貴, 加藤 陽子, 後藤 晶子, 坂口 佐知, 徳山 美香, 石井 栄三郎, 石田 也寸志, 中舘 尚也, 真部 淳, 小原 明, 東京小児がん研究グループ(TCCSG)QOL委員会
日本小児血液・がん学会雑誌, 52, 4, 345, 345, (一社)日本小児血液・がん学会, 2015年10月
日本語

Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia
Yoichi Tanaka, Motohiro Kato, Daisuke Hasegawa, Kevin Y. Urayama, Hisaya Nakadate, Kensuke Kondoh, Kozue Nakamura, Katsuyoshi Koh, Takako Komiyama, Atsushi Manabe
BRITISH JOURNAL OF HAEMATOLOGY, 171, 1, 109, 115, WILEY-BLACKWELL, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Genotyping of TPMT prior to 6-mercaptopurine (6-MP) administration in acute lymphoblastic leukaemia (ALL) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6-MP myelotoxicity, but rarity of TPMT variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric ALL patients for NUDT15 rs116855232, a 6-MP toxicity-related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6-MP dose reduction, therapy interruption and event-free survival. The allele frequency of rs116855232 was 0.16, and leucopenia was more common in carriers of the T allele (odds ratio, 7.20; 95% confidence interval, 2.49-20.80; P = 2.7 x 10(-4)). As leucopenia results in 6-MP dose reduction, we observed average doses during maintenance therapy of 40.7, 29.3 and 8.8 mg/m(2) for patients with CC, CT and TT genotypes, respectively (P < 0.001). Hepatotoxicity was observed only in CC genotype patients. Event-free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6-MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity-related locus in Asians to date. Considerations for clinical application may be warranted.

Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia
Yoichi Tanaka, Motohiro Kato, Daisuke Hasegawa, Kevin Y. Urayama, Hisaya Nakadate, Kensuke Kondoh, Kozue Nakamura, Katsuyoshi Koh, Takako Komiyama, Atsushi Manabe
British Journal of Haematology, 171, 1, 109, 115, Blackwell Publishing Ltd, 2015年10月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Genotyping of TPMT prior to 6-mercaptopurine (6-MP) administration in acute lymphoblastic leukaemia (ALL) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6-MP myelotoxicity, but rarity of TPMT variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric ALL patients for NUDT15 rs116855232, a 6-MP toxicity-related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6-MP dose reduction, therapy interruption and event-free survival. The allele frequency of rs116855232 was 0·16, and leucopenia was more common in carriers of the T allele (odds ratio, 7·20
95% confidence interval, 2·49-20·80
P = 2·7 × 10-4). As leucopenia results in 6-MP dose reduction, we observed average doses during maintenance therapy of 40·7, 29·3 and 8·8 mg/m2 for patients with CC, CT and TT genotypes, respectively (P <
0·001). Hepatotoxicity was observed only in CC genotype patients. Event-free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6-MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity-related locus in Asians to date. Considerations for clinical application may be warranted.

ダサチニブ投与中に両側肺下胸水を認めたフィラデルフィア染色体陽性急性リンパ性白血病の男児
吉本 優里, 熊本 忠史, 木村 俊介, 平林 真介, 細谷 要介, 長谷川 大輔, 真部 淳
日本小児血液・がん学会雑誌, 52, 4, 309, (NPO)日本小児血液・がん学会, 2015年10月

VincristineとActinomycin Dによる化学療法が奏効し下肢切断を免れているinfantile fibrosarcomaの一例
細谷 要介, 吉本 優里, 吉原 宏樹, 長谷川 大輔, 熊本 忠史, 川野 孝文, 迫田 晃子, 松藤 凡, 真部 淳
日本小児血液・がん学会雑誌, 52, 4, 304, (NPO)日本小児血液・がん学会, 2015年10月

体細胞ヘテロ接合性CBL変異が長期に残存したJMML(Long-term persistence of somatic heterozygous CBL mutation in JMML)
平林 真介, 長谷川 大輔, 周尾 卓也, 村松 秀城, 坂下 一夫, 小島 勢二, 小池 健一, 真部 淳
日本小児血液・がん学会雑誌, 52, 4, 277, (NPO)日本小児血液・がん学会, 2015年10月

小児悪性腫瘍患者におけるClostridium Difficile腸炎のリスク(Risk factors for Clostridium difficile associated diarrhea among pediatric cancer patients)
代田 惇朗, 吉原 宏樹, 稲井 郁子, 吉本 優里, 平林 真介, 細谷 要介, 長谷川 大輔, 石田 也寸志, 浦山 ケビン, 真部 淳
日本小児血液・がん学会雑誌, 52, 4, 243, (NPO)日本小児血液・がん学会, 2015年10月

再生不良性貧血・骨髄増殖性疾患 治療関連骨髄異形成症候群44例の臨床像(Aplastic anemia and myeloproliferative disorder Clinical characteristics of 44 cases with therapy-related myelodysplastic syndrome in childhood)
長谷川 大輔, 濱 麻人, 野沢 和江, 平林 真介, 渡邉 健一郎, 土田 昌宏, 伊藤 雅文, 小島 勢二, 中畑 龍俊, 真部 淳
日本小児血液・がん学会雑誌, 52, 4, 208, (NPO)日本小児血液・がん学会, 2015年10月

わが国の小児がん医療提供体制について考える 小児がんに対するトータルケアと医療提供体制
長谷川 大輔, 小澤 美和, 真部 淳, 細谷 亮太
日本小児血液・がん学会雑誌, 52, 4, 189, (NPO)日本小児血液・がん学会, 2015年10月

Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children’s Cancer Study Group
Daisuke Tomizawa, Motohiro Kato, Hiroyuki Takahashi, Junya Fujimura, Takeshi Inukai, Takashi Fukushima, Nobutaka Kiyokawa, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara
International Journal of Hematology, 102, 5, 602, 610, Springer-Verlag Tokyo, 2015年09月26日, ［査読有り］
英語, 研究論文（学術雑誌）, Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children’s Cancer Study Group ALL studies L95–14, L99–15, L99–1502, L04–16, and L07–1602 (1995–2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1–15 years) and 27,690/μL (range 1800–1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols
Daisuke Tomizawa, Tomoyuki Watanabe, Ryoji Hanada, Keizo Horibe, Yasuo Horikoshi, Shotaro Iwamoto, Akitoshi Kinoshita, Hiroshi Moritake, Hideki Nakayama, Akira Shimada, Takashi Taga, Hiroyuki Takahashi, Akio Tawa, Kiminori Terui, Hiroki Hori, Yoshifumi Kawano, Atsushi Kikuta, Atsushi Manabe, Souichi Adachi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 102, 3, 318, 326, SPRINGER JAPAN KK, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）, As past studies of adolescent and young adults (AYA) with acute myeloid leukemia (AML) reported conflicting results, we conducted a retrospective analysis using data from three Japanese pediatric AML studies. Among the 782 patients with de novo AML, 44 were classified as AYA (age a parts per thousand yen15 years at diagnosis), 164 as infants (0-1 year), 413 as younger children (2-11 years), and 161 as older children (12-14 years). While the 5-year event-free survival rate of AYA was not different among the groups, the five-year survival rate (54.7 %) was significantly lower than that of the other three groups (P = 0.019): 68.7 % for infants, 73.2 % for younger children, and 75.5 % for older children. No difference in the 5-year cumulative incidence of relapse was observed, but treatment-related death (TRD) of AYA was significantly higher (29.4 %) than that in infants (14.8 %), younger children (10.2 %), and older children (13.8 %). Multivariate analysis showed age a parts per thousand yen15 years old at diagnosis was associated with both poor survival rate and high TRD. Adolescents with AML had inferior survival due to a higher incidence of TRD, especially after failure of initial frontline treatment.

肋骨の多発溶骨性変化をきたしているGorham病の発症10年後の呼吸機能
梅原 直, 熊本 忠史, 真部 淳
日本小児呼吸器学会雑誌, 26, Suppl., 147, 日本小児呼吸器学会, 2015年09月

【内科が使う自己注射薬】 血液に作用する自己注射薬 G-CSF製剤の在宅自己注射
平林 真介, 真部 淳
診断と治療, 103, 9, 1223, (株)診断と治療社, 2015年09月
1 G-CSF製剤は骨髄前駆細胞から顆粒球への増殖分化を促すと同時に顆粒球の機能を高めるバイオ医薬品であり、幅広く臨床応用されている。2 再生不良性貧血と先天性好中球減少症においてG-CSF製剤は有意に感染が減少し、在宅自己注射の適応が承認された。3 G-CSF製剤の長期投与に伴いMDS/AMLへの移行が報告されており、漫然とした使用は避ける必要がある。(著者抄録)

Multidrug resistance protein 4 (MRP4) polymorphisms impact the 6-mercaptopurine dose tolerance during maintenance therapy in Japanese childhood acute lymphoblastic leukemia
Y. Tanaka, A. Manabe, H. Fukushima, R. Suzuki, H. Nakadate, K. Kondoh, K. Nakamura, K. Koh, T. Fukushima, M. Tsuchida, K. Koike, N. Kiyokawa, E. Noguchi, R. Sumazaki, T. Komiyama
Pharmacogenomics Journal, 15, 4, 380, 384, Nature Publishing Group, 2015年08月25日
英語, 研究論文（学術雑誌）, Multidrug resistance protein 4 (MRP4) is involved in the efflux of nucleoside derivatives and has a role in the determination of drug sensitivity. We investigated the relationship between MRP4 genetic polymorphisms and doses of the 6-mercaptopurine (6-MP) and methotrexate. Further, we evaluated the frequency of therapeutic interruption during maintenance therapy in Japanese children with acute lymphoblastic leukemia (ALL). Ninety-four patients received an initial 6-MP dose in the range of 30-50 mg m-2 in this analysis. Patients with homozygous variant allele in any of MRP4 G2269A, C912A and G559T required high frequency of 6-MP dose reduction compared with non-homozygous individuals. Average 6-MP dose for patients with homozygous variant allele on either MRP4 or inosine triphosphate pyrophosphatase was significantly lower than that for patients with non-homozygous variant allele during maintenance therapy (30.5 versus 40.0 mg m-2, P=0.024). Therefore, MRP4 genotyping may be useful for personalizing the therapeutic dose of 6-MP during the ALL maintenance therapy in Japanese.

Review article series on the state of recent evidence in childhood cancer
Atsushi Manabe
PEDIATRICS INTERNATIONAL, 57, 4, 515, 515, WILEY-BLACKWELL, 2015年08月, ［査読有り］
英語

Cytogenetics and clinical features of pediatric myelodysplastic syndrome in Japan (vol 100, pg 478, 2014)
Koichi Moriwaki, Atsushi Manabe, Takeshi Taketani, Akira Kikuchi, Tatsutoshi Nakahata, Yasuhide Hayashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 102, 2, 249, 249, SPRINGER JAPAN KK, 2015年08月, ［査読有り］
英語

Multidrug resistance protein 4 (MRP4) polymorphisms impact the 6-mercaptopurine dose tolerance during maintenance therapy in Japanese childhood acute lymphoblastic leukemia
Y. Tanaka, A. Manabe, H. Fukushima, R. Suzuki, H. Nakadate, K. Kondoh, K. Nakamura, K. Koh, T. Fukushima, M. Tsuchida, K. Koike, N. Kiyokawa, E. Noguchi, R. Sumazaki, T. Komiyama
PHARMACOGENOMICS JOURNAL, 15, 4, 380, 384, NATURE PUBLISHING GROUP, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Multidrug resistance protein 4 (MRP4) is involved in the efflux of nucleoside derivatives and has a role in the determination of drug sensitivity. We investigated the relationship between MRP4 genetic polymorphisms and doses of the 6-mercaptopurine (6-MP) and methotrexate. Further, we evaluated the frequency of therapeutic interruption during maintenance therapy in Japanese children with acute lymphoblastic leukemia (ALL). Ninety-four patients received an initial 6-MP dose in the range of 30-50 mg m(-2) in this analysis. Patients with homozygous variant allele in any of MRP4 G2269A, C912A and G559T required high frequency of 6-MP dose reduction compared with non-homozygous individuals. Average 6-MP dose for patients with homozygous variant allele on either MRP4 or inosine triphosphate pyrophosphatase was significantly lower than that for patients with non-homozygous variant allele during maintenance therapy (30.5 versus 40.0 mg m(-2), P = 0.024). Therefore, MRP4 genotyping may be useful for personalizing the therapeutic dose of 6-MP during the ALL maintenance therapy in Japanese.

CD10陰性B前駆細胞性急性リンパ芽球性白血病の新たな亜群EP300-ZNF384　　　　　　　　　　　　　　　
寺田 和樹, 清河 信敬, 牛腸 義宏, 谷口 明徳, 石橋 武士, 橋本 亙, 大隅 朋生, 大木 健太郎, 福島 敬, 康 勝好, 真部 淳, 小原 明
Cytometry Research, 25, Suppl., 56, 56, (一社)日本サイトメトリー学会, 2015年07月
日本語

消化管出血を呈した青色ゴムまり様母斑症候群の1例
栗山 絢子, 石田 悠志, 吉本 優里, 平林 真介, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 真部 淳
日本小児科学会雑誌, 119, 6, 1029, (公社)日本小児科学会, 2015年06月

Long-term outcome of six months maintenance chemotherapy for ALL in children: TCCSG L92-13E study.
Motohiro Kato, Atsushi Manabe, Sae Ishimaru, Masafumi Seki, Kenichi Yoshida, Daisuke Tomizawa, Daisuke Hasegawa, Takeshi Inukai, Yuki Arakawa, Takahiro Aoki, Mayuko Okuya, Kiyohiko Kaizu, Keisuke Kato, Yuichi Taneyama, Seishi Ogawa, Katsuyoshi Koh, Masahiro Tsuchida, Akira Ohara
JOURNAL OF CLINICAL ONCOLOGY, 33, 15, AMER SOC CLINICAL ONCOLOGY, 2015年05月, ［査読有り］
英語

Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph(+)ALL04
Atsushi Manabe, Hirohide Kawasaki, Hiroyuki Shimada, Itaru Kato, Yuichi Kodama, Atsushi Sato, Kimikazu Matsumoto, Keisuke Kato, Hiromasa Yabe, Kazuko Kudo, Motohiro Kato, Tomohiro Saito, Akiko M. Saito, Masahito Tsurusawa, Keizo Horibe
CANCER MEDICINE, 4, 5, 682, 689, WILEY-BLACKWELL, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Incorporation of imatinib into chemotherapeutic regimens has improved the prognosis of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). We investigated a role of imatinib immediately before hematopoietic stem cell transplantation (HSCT). Children with Ph(+)ALL were enrolled on JPLSG Ph(+)ALL 04 Study within 1week of initiation of treatment for ALL. Treatment regimen consisted of Induction phase, Consolidation phase, Reinduction phase, 2weeks of imatinib monotherapy phase, and HSCT phase (Etoposide+CY+TBI conditioning). Minimal residual disease (MRD), the amount of BCR-ABL transcripts, was measured with the real-time PCR method. The study was registered in UMIN-CTR: UMIN ID C000000290. Forty-two patients were registered and 36 patients (86%) achieved complete remission (CR). Eight of 17 patients (47%) who had detectable MRD at the beginning of imatinib monotherapy phase showed disappearance or decrease in MRD after imatinib treatment. Consequently, 26 patients received HSCT in the first CR and all the patients had engraftment and no patients died because of complications of HSCT. The 4-year event-free survival rates and overall survival rates among all the 42 patients were 54.1 +/- 7.8% and 78.1 +/- 6.5%, respectively. Four of six patients who did achieve CR and three of six who relapsed before HSCT were salvaged with imatinib-containing chemotherapy and subsequently treated with HSCT. The survival rate was excellent in this study although all patients received HSCT. A longer use of imatinib concurrently with chemotherapy should eliminate HSCT in a subset of patients with a rapid clearance of the disease.

周期性好中球減少症合併患者に婦人科手術を施行した一例
大垣 洋子, 塩田 恭子, 山田 梨紗子, 和泉 紀子, 岩瀬 純, 水野 吉章, 秋谷 文, 平林 真介, 真部 淳
日本産婦人科・新生児血液学会誌, 25, 1, 32, 日本産婦人科・新生児血液学会, 2015年05月
42歳(0回経妊婦)。周期性好中球減少症の既往があり、今回、卵巣嚢腫摘出術および子宮筋腫核出術目的に当科入院となった。約2ヵ月にわたり好中球の変動を確認し、最低値の時期を過ぎる頃に手術日を設定したが、予定日の3日前よりG-CSF製剤を投与するも好中球数は改善せず、手術は延期となった。遺伝子検査でELA2変異を認め、G-CSF製剤が有効な型であったため、再度手術日を設定し8日前よりG-CSF製剤の投与を行った。周術期の予防的抗生剤はVCM、CFPM、MNZの点滴とし、右卵巣嚢腫摘出と子宮筋腫核出術を施行し得た。術後の経過は良好で、術後5日目に軽快退院した。

Psychosocial difficulties in adolescent and young adult survivors of childhood cancer
Yuko Takei, Akiko Ogata, Miwa Ozawa, Hiroshi Moritake, Kei Hirai, Atsushi Manabe, Shin-ichi Suzuki
PEDIATRICS INTERNATIONAL, 57, 2, 239, 246, WILEY-BLACKWELL, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）, BackgroundWith a large number of children surviving cancer worldwide, numerous investigations have assessed psychological and social adjustment among childhood cancer survivors. According to these studies, it is unclear whether childhood cancer survivors successfully adjust to daily life after being discharged from hospital, especially for adolescent and young adult survivors who have unique needs and concerns. The primary aim of this study was to identify the factors underlying psychosocial difficulties faced by adolescent and young adult survivors in their day-to-day lives after being discharged from hospital.
MethodsSemi-structured interviews were conducted. Twenty-five childhood cancer survivors were recruited from two regional cancer institutions in Japan. Content analysis was applied to the responses.
ResultsNineteen attributes were extracted and classified into four categories as follows: physical difficulties, interpersonal difficulties, behavioral difficulties, and uncertainty about the future. The attributes indicated by >50% of the participants were I am worried about not feeling well, I have difficulty continuing treatment in daily life, I have difficulty moving my body, I have to be absent from school or work because of illness, and I am left behind academically.
ConclusionsThis study identified important factors of psychosocial day-to-day difficulties. Clinically, these results suggest that it is important to watch for these signs and to provide early support to survivors so that their daily life and development are not hindered by the treatment and its side-effects, and to offer long-term support focusing on individual patient characteristics such as sex, age, and cancer history.

Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children
Rintaro Ono, Daisuke Hasegawa, Shinsuke Hirabayashi, Takahiro Kamiya, Kenichi Yoshida, Satoko Yonekawa, Chitose Ogawa, Ryota Hosoya, Tsutomu Toki, Kiminori Terui, Etsuro Ito, Atsushi Manabe
EUROPEAN JOURNAL OF PEDIATRICS, 174, 4, 525, 531, SPRINGER, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）, GATA1 mutations are found almost exclusively in children with myeloid proliferations related to Down syndrome (DS). Here, we report two phenotypically and cytogenetically normal children with acute megakaryoblastic leukemia (AMKL) whose blasts had both acquired trisomy 21 and GATA1 mutation. Patient 1 was diagnosed with transient abnormal myelopoiesis in the neonatal period. Following spontaneous improvement of the disease, leukemic blasts increased 7 months later. He received less intensive chemotherapy, and he is now 6 years old in complete remission. Patient 2 was diagnosed with AMKL at the age of 18 months. Although he received intensive chemotherapy and a cord blood transplantation, he died without gaining remission. In both cases, trisomy 21 and GATA1 mutation were detected only in leukemic blasts, but not in germline samples. Based on a literature review, we identified reports describing 14 non-DS AMKL with GATA1 mutation and acquired trisomy 21. Of those, 12 cases were diagnosed during the neonatal period, whereas the remaining 2 cases were diagnosed at the age of 22 and 31 months, respectively.
Conclusion: These cases suggest that GATA1 mutation may cooperate with the additional chromosome 21 in developing myeloid proliferations even in non-DS patients.

Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children.
Rintaro Ono, Daisuke Hasegawa, Shinsuke Hirabayashi, Takahiro Kamiya, Kenichi Yoshida, Satoko Yonekawa, Chitose Ogawa, Ryota Hosoya, Tsutomu Toki, Kiminori Terui, Etsuro Ito, Atsushi Manabe
European journal of pediatrics, 174, 4, 525, 31, 2015年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, UNLABELLED: GATA1 mutations are found almost exclusively in children with myeloid proliferations related to Down syndrome (DS). Here, we report two phenotypically and cytogenetically normal children with acute megakaryoblastic leukemia (AMKL) whose blasts had both acquired trisomy 21 and GATA1 mutation. Patient 1 was diagnosed with transient abnormal myelopoiesis in the neonatal period. Following spontaneous improvement of the disease, leukemic blasts increased 7 months later. He received less intensive chemotherapy, and he is now 6 years old in complete remission. Patient 2 was diagnosed with AMKL at the age of 18 months. Although he received intensive chemotherapy and a cord blood transplantation, he died without gaining remission. In both cases, trisomy 21 and GATA1 mutation were detected only in leukemic blasts, but not in germline samples. Based on a literature review, we identified reports describing 14 non-DS AMKL with GATA1 mutation and acquired trisomy 21. Of those, 12 cases were diagnosed during the neonatal period, whereas the remaining 2 cases were diagnosed at the age of 22 and 31 months, respectively. CONCLUSION: These cases suggest that GATA1 mutation may cooperate with the additional chromosome 21 in developing myeloid proliferations even in non-DS patients.

小児がん治療の最前線 Pharmacogenomics and Translational Medicine
真部 淳
日本薬学会年会要旨集, 135年会, 1, 348, (公社)日本薬学会, 2015年03月

小児がん治療30年間の進歩 予後の改善と患者・家族への支援
真部 淳
聖路加国際大学紀要, 1, 29, 聖路加国際大学, 2015年03月

小児科領域の国際専門誌に論文を掲載するコツ
真部 淳
小児科, 56, 3, 311, 金原出版(株), 2015年03月

Transplantation for juvenile myelomonocytic leukemia: a retrospective study of 30 children treated with a regimen of busulfan, fludarabine, and melphalan
Miharu Yabe, Yoshitoshi Ohtsuka, Kenichiro Watanabe, Jiro Inagaki, Nao Yoshida, Kazuo Sakashita, Harumi Kakuda, Hiromasa Yabe, Hidemitsu Kurosawa, Kazuko Kudo, Atsushi Manabe
INTERNATIONAL JOURNAL OF HEMATOLOGY, 101, 2, 184, 190, SPRINGER JAPAN KK, 2015年02月, ［査読有り］
英語, 研究論文（学術雑誌）, We report the outcomes of 30 patients with juvenile myelomonocytic leukemia (JMML) who received unmanipulated hematopoietic stem cell transplantation (HSCT) with oral or intravenous busulfan, fludarabine, and melphalan between 2001 and 2011. Mutations in PTPN11 were detected in 15 patients. Six patients received human leukocyte antigen (HLA)-matched HSCT from related donors, and 24 patients received HSCT from alternative donors, including 13 HLA-mismatched donors. Primary engraftment failed in five patients, all of whom had received allografts from HLA-mismatched donors. HLA-mismatched HSCT resulted in poorer event-free survival than HLA-matched HSCT (28.8 vs. 70.6 %). Three patients died of transplantation-related causes, and eight patients experienced hematological relapse (including five patients who died due to disease progression). Eight patients received a second HSCT, and four of these patients have survived. The 5-year estimated overall survival for all patients was 72.4: 88.9 % for the patients without a mutation in PTPN11 (n = 10) and 58.3 % for the patients with a mutation in PTPN11 (n = 15) (P = 0.092). The conditioning regimen reported in the present study achieved hematological and clinical remission in > 50 % of patients with JMML who received HSCT from alternative donors, and may also be effective for JMML patients with PTPN11 mutation.

無呼吸、重症下気道感染を来したHuman Rhinovirusの乳児3例
代田 惇朗, 辻本 信一, 稲井 郁子, 吉本 優里, 石田 悠志, 野村 耕太郎, 梅原 直, 小澤 美和, 真部 淳, 草川 功
日本小児科学会雑誌, 119, 2, 511, 511, (公社)日本小児科学会, 2015年02月
日本語

消化管出血を呈したBlue rubber bleb nevus syndromeの一例
栗山 絢子, 吉本 優里, 平林 真介, 長谷川 大輔, 小澤 美和, 草川 功, 真部 淳, 嶋田 明, 末延 聡一
日本小児科学会雑誌, 119, 2, 419, 419, (公社)日本小児科学会, 2015年02月
日本語

頸部リンパ節炎の治療に難渋した自己免疫性好中球減少症の2例
吉本 優里, 代田 惇朗, 平林 真介, 長沖 優子, 細谷 要介, 長谷川 大輔, 稲井 郁子, 小澤 美和, 草川 功, 真部 淳
日本小児科学会雑誌, 119, 2, 414, (公社)日本小児科学会, 2015年02月

英語論文の書き方
真部 淳
日本小児科学会雑誌, 119, 2, 167, (公社)日本小児科学会, 2015年02月

Outcome of pediatric acute lymphoblastic leukemia with very late relapse: a retrospective analysis by the Tokyo Children's Cancer Study Group (TCCSG)
Motohiro Kato, Atsushi Manabe, Akiko M. Saito, Katsuyoshi Koh, Takeshi Inukai, Chitose Ogawa, Hiroyuki Goto, Masahiro Tsuchida, Akira Ohara
INTERNATIONAL JOURNAL OF HEMATOLOGY, 101, 1, 52, 57, SPRINGER JAPAN KK, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Relapse period is strongly associated with second relapse risk in relapsed acute lymphoblastic leukemia (ALL) in children. In this context, the treatment outcome of very late relapse should be better; however, data regarding very late relapse is limited. We retrospectively analyzed the outcomes of two consecutive Tokyo Children's Cancer Study Group (TCCSG) ALL trials (1995-2004) with a focus on late relapse, which was divided into two categories: late relapse (6-24 months from the end of therapy, n = 48) and very late relapse (> 24 months from the end of therapy, n = 57). Forty-three patients (29 late relapse and 14 very late relapse) received allogeneic hematopoietic stem cell transplantation (HSCT) at second remission. The event-free survival (EFS) probabilities of late relapse and very late relapse were 54.5 +/- A 7.3 and 64.8 +/- A 6.8 % at 7 years, respectively (P = 0.36), and were not significantly different. However, the second relapse incidence of late relapse (34.7 +/- A 7.1 %) was higher than that of very late relapse (15.5 +/- A 5.1 %, P = 0.03). The second relapse risk was low for very late relapse ALL, which suggests that these patients should be treated without allogeneic HSCT.

Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia
Charlotte M. Niemeyer, Mignon L. Loh, Annamaria Cseh, Todd Cooper, Christopher C. Dvorak, Rebecca Chan, Blanca Xicoy, Ulrich Germing, Seiji Kojima, Atsushi Manabe, Michael Dworzak, Barbara De Moerloose, Jan Stary, Owen P. Smith, Riccardo Masetti, Albert Catala, Eva Bergstraesser, Marek Ussowicz, Oskana Fabri, Andre Baruchel, Helene Cave, Michel Zwaan, Franco Locatelli, Henrik Hasle, Marry M. van den Heuvel-Eibrink, Christian Flotho, Ayami Yoshimi
HAEMATOLOGICA, 100, 1, 17, 22, FERRATA STORTI FOUNDATION, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I-II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia.

Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia
Charlotte M. Niemeyer, Mignon L. Loh, Annamaria Cseh, Todd Cooper, Christopher C. Dvorak, Rebecca Chan, Blanca Xicoy, Ulrich Germing, Seiji Kojima, Atsushi Manabe, Michael Dworzak, Barbara De Moerloose, Jan Starý, Owen P. Smith, Riccardo Masetti, Albert Catala, Eva Bergstraesser, Marek Ussowicz, Oskana Fabri, André Baruchel, Hélène Cavé, Michel Zwaan, Franco Locatelli, Henrik Hasle, Marry M. Van Den Heuvel-Eibrink, Christian Flotho, Ayami Yoshimi
Haematologica, 100, 1, 17, 22, Ferrata Storti Foundation, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I-II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia.

小児急性リンパ性白血病の維持療法期間におけるメルカプトプリン及びメトトレキサート投与量の推移:～単施設における検討～
歌野 智之, 田中 庸一, 木津 純子, 神谷 尚宏, 小川 千登世, 石田 也寸志, 細谷 亮太, 真部 淳
日本小児血液・がん学会雑誌, 52, 5, 399, 404, 日本小児血液・がん学会, 2015年
日本語, 【背景】メルカプトプリン（6-MP）及びメトトレキサート（MTX）の臨床効果や副作用は個体差が大きく，個々によって至適投与量は大きく異なる事が知られている．本研究は，両薬剤の投与量推移を調査し，患者背景及び再発との関連性について調査した．【方法】1995年4月～2010年3月の期間に当施設で急性リンパ性白血病（ALL）と診断され，維持療法が終了した患児を対象とした．両薬剤の投与量推移を調査し，投与量推移別に患者背景（性別，診断時：白血球数，年齢，immunophenotype，維持療法開始時：体表面積，Prednisolone反応性，リスク分類，肥満度）を比較した．また，再発患者と非再発患者の6-MP及びMTXの投与量推移を比較した．【結果】維持療法開始1年以内に6-MP投与量の変更を要した患児は50名中34名（増量20名，減量14名），MTX投与量の変更を要した患児は50名中18名（増量

Long-Term Outcome of Six Months Maintenance Chemotherapy for ALL in Children: An Extended Follow up Study of TCCSG L92-13
Motohiro Kato, Atsushi Manabe, Sae Ishimaru, Daisuke Tomizawa, Daisuke Hasegawa, Takeshi Inukai, Yuki Arakawa, Takahiro Aoki, Mayuko Okuya, Kiyohiko Kaizu, Keisuke Kato, Yuichi Taneyama, Katsuyoshi Koh, Masahiro Tsuchida, Akira Ohara
BLOOD, 124, 21, AMER SOC HEMATOLOGY, 2014年12月, ［査読有り］
英語

Hematopoietic Stem Cell Transplantation for Patients with Refractory Cytopenia of Childhood
Daisuke Hasegawa, Shinsuke Hirabayashi, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Atsuko Masunaga, Ayami Yoshimi, Asahito Hama, Seiji Kojima, Masafumi Ito, Tatsutoshi Nakahata, Atsushi Manabe
BLOOD, 124, 21, AMER SOC HEMATOLOGY, 2014年12月, ［査読有り］
英語

集学的治療を行った仙尾部原発卵黄嚢腫瘍の1例
上野 浩生, 長谷川 大輔, 辻本 信一, 小野 林太郎, 吉本 優里, 細谷 要介, 吉原 宏樹, 熊本 忠史, 川野 孝文, 迫田 晃子, 野崎 太希, 関口 建次, 中面 哲也, 真部 淳
日本小児血液・がん学会雑誌, 51, 5, 569, (NPO)日本小児血液・がん学会, 2014年12月

Cytogenetics and clinical features of pediatric myelodysplastic syndrome in Japan
Koichi Moriwaki, Atsushi Manabe, Takeshi Taketani, Akira Kikuchi, Tatsutoshi Nakahata, Yasuhide Hayashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 100, 5, 478, 484, SPRINGER JAPAN KK, 2014年11月, ［査読有り］
英語, 研究論文（学術雑誌）, We analyzed the cytogenetics and clinical features of pediatric myelodysplastic syndrome (MDS) in Japan. Data on patients (<16 years) diagnosed with MDS from 1990 to 2000 were retrospectively collected from pediatric hematologists in 234 institutions. Chromosome analysis was successfully performed in 255 of 277 MDS patients. The numbers of patients with refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB), refractory anemia with excess of blasts in transformation (RAEBt), chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia were 67 (24 %), 51 (18 %), 51 (18 %), 20 (7 %), and 65 (23 %), respectively. The other 23 patients (8 %) could not be classified specifically. The distribution of childhood MDS in Japan according to the French-American-British subclassification was similar to that in other countries. However, we identified a higher incidence of therapy-related cases. As for relationship between cytogenetics and prognoses, abnormal karyotypes were related to poorer prognoses than normal karyotype (P < 0.01). However, patients with trisomy 8 had prognoses comparable to those with normal karyotypes. Complex karyotypes were associated with poorer prognoses among RAEB and RAEBt patients. In conclusion, prognosis of pediatric MDS is related to cytogenetics. A more precise diagnosis and classification system is needed for childhood MDS.

【難治性貧血-診断と病態・治療の進歩-】 小児科領域貧血の診断と病態・治療の進歩 先天性疾患
真部 淳
最新医学, 69, 11, 2159, (株)最新医学社, 2014年11月
小児の先天性骨髄不全は,頻度はまれながら多くの疾患がある.先天性骨髄不全症候群は臨床症状や通常の臨床検査では診断が困難であり,遺伝子の検索が重要であるが,近年多くの疾患で責任遺伝子が同定されてきた.小児の先天性骨髄不全症候群は再生不良性貧血あるいは骨髄異形成症候群とのオーバーラップも多く,中央診断を通じた丁寧な診断と多施設共同治療研究が必須である.(著者抄録)

無症候の母から出生した新生児ループスの1例
岡崎 幹子, 吉本 優里, 代田 惇朗, 石田 悠志, 島袋 林秀, 稲井 郁子, 小澤 美和, 草川 功, 真部 淳
日本小児科学会雑誌, 118, 11, 1667, (公社)日本小児科学会, 2014年11月

【急性リンパ性白血病をめぐる最近の進歩】 小児急性リンパ性白血病の治療戦略
石田 悠志, 真部 淳
血液内科, 69, 5, 637, (有)科学評論社, 2014年11月

小児がん診断後の二次がん発症に関する疫学研究 15病院における後ろ向きコホート(Secondary cancers after cancer diagnosis in childhood: A hospital-based retrospective cohort study in Japan)
石田 也寸志, 邱 冬梅, 前田 美穂, 藤本 純一郎, 気賀沢 寿人, 小林 良二, 佐藤 真穂, 岡村 純, 吉永 信治, 力石 健, 七野 浩之, 清谷 知賀子, 工藤 寿子, 浅見 恵子, 堀 浩樹, 川口 浩史, 稲田 浩子, 足立 壮一, 真部 淳, 黒田 達夫
日本小児血液・がん学会雑誌, 51, 4, 261, 261, (一社)日本小児血液・がん学会, 2014年10月
英語

小児がん患児のきょうだいと母親のサポート知覚の特徴
長尾 愛美, 小澤 美和, 小川 祐子, 武井 優子, 竹内 恵美, 長谷川 由美, 真部 淳, 鈴木 伸一
日本小児血液・がん学会雑誌, 51, 4, 375, 375, (一社)日本小児血液・がん学会, 2014年10月
日本語

長期入院中の兄弟に対する集学的サポート(part 1) PedsQL 4.0総合コア尺度を用いた兄弟のQOL評価(Multidisciplinary support for siblings of long-term inpatients(part 1): Evaluation of siblings' quality of life using the PedsQL 4.0 Generic Core Scales)
野村 耕太郎, 若林 優, 植松 温子, 春山 智恵子, 三浦 絵莉子, 石田 智美, 後藤 真弥, 北川 千恵, 山本 光映, 小澤 美和, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 375, 375, (NPO)日本小児血液・がん学会, 2014年10月
英語

高機能自閉症スペクトラム障害を抱える3歳男児の、入院中の心理的支援 骨髄移植をチームで支える
阿佐美 百合子, 春山 智恵子, 後藤 真弥, 北川 知恵, 熊谷 祐美, 平田 美佳, 山本 光映, 小澤 美和, 長谷川 大輔, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 374, (NPO)日本小児血液・がん学会, 2014年10月

神経下垂体部胚細胞腫瘍の化学療法中に点鼻あるいは経口デスモプレシン製剤を用いて尿崩症管理を行った5例
木村 俊介, 細谷 要介, 石田 悠志, 野村 耕太郎, 吉本 優里, 吉原 宏樹, 長谷川 大輔, 伊藤 純子, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 335, (NPO)日本小児血液・がん学会, 2014年10月

小児がん患者における長期留置型中心静脈カテーテル合併症のリスクファクターについて(Risk factors of long-term central venous catheters (CVCS) complication in children with hemato-oncological disorders)
迫田 晃子, 川野 孝文, 細谷 要介, 吉原 宏樹, 平林 真介, 長谷川 大輔, 小澤 美和, 真部 淳, 松藤 凡
日本小児血液・がん学会雑誌, 51, 4, 334, 334, (NPO)日本小児血液・がん学会, 2014年10月
英語

当院で経験した神経芽腫Stage 4Sの2例
吉本 優里, 野村 耕太郎, 石田 悠志, 平林 真介, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 細谷 亮太, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 287, (NPO)日本小児血液・がん学会, 2014年10月

急性前骨髄球性白血病M3 variantの2例
石田 悠志, 松井 俊大, 木村 俊介, 野村 耕太郎, 吉本 優里, 平林 真介, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 熊本 忠史, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 269, (NPO)日本小児血液・がん学会, 2014年10月

多職種による長期入院児のきょうだい支援(part 2) きょうだいと医療者、きょうだい同士をつなげる取り組み(Multidisciplinary team approach to sibling support: The bridge-building of siblings, and of siblings and medical staff)
若林 優, 植松 温子, 春山 智恵子, 三浦 絵莉子, 石田 智美, 後藤 真弥, 北川 千恵, 野村 耕太郎, 山本 光映, 真部 淳, 小澤 美和
日本小児血液・がん学会雑誌, 51, 4, 259, 259, (NPO)日本小児血液・がん学会, 2014年10月
英語

小児がん患者における精神身体症状発現のリスク因子の検討(Risk factors for psychosomatic symptoms among pediatric cancer patients)
前田 謙一, 辻本 信一, 長谷川 大輔, 浦山 ケビン, 阿佐美 百合子, 小澤 美和, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 258, 258, (NPO)日本小児血液・がん学会, 2014年10月
英語

消化管出血を伴う青色ゴムまり様母斑症候群の乳児例(An infant of blue rubber bleb nevus syndrome with gastrointestinal bleeding)
平林 真介, 栗山 絢子, 石田 悠志, 吉本 優里, 細谷 要介, 吉原 宏樹, 川野 孝文, 迫田 晃子, 森田 有香, 中村 仁美, 衛藤 光, 鈴木 高祐, 末延 聡一, 長谷川 大輔, 真部 淳
日本小児血液・がん学会雑誌, 51, 4, 242, (NPO)日本小児血液・がん学会, 2014年10月

【小児血液疾患-よくわかる最新知見-】 造血器悪性疾患 若年性骨髄単球性白血病
平林 真介, 真部 淳
小児科, 55, 11, 1745, 金原出版(株), 2014年10月

Genomic evaluations of childhood acute lymphoblastic leukemia susceptibility across race/ethnicities (第76回日本血液学会学術集会 教育講演特集号) -- (小児疾患)
URAYAMA Kevin Y, MANABE Atsushi
臨床血液, 55, 10, 2242, 2248, The Japanese Society of Hematology, 2014年10月, ［査読有り］

Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification
Daisuke Hasegawa, Xiaojuan Chen, Shinsuke Hirabayashi, Yasushi Ishida, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Atsuko Masunaga, Ayami Yoshimi, Asahito Hama, Seiji Kojima, Masafumi Ito, Tatsutoshi Nakahata, Atsushi Manabe
BRITISH JOURNAL OF HAEMATOLOGY, 166, 5, 758, 766, WILEY-BLACKWELL, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, This study analysed 65 children who were prospectively registered between 1999 and 2008 and fulfilled the World Health Organization 2008 criteria of refractory cytopenia of childhood (RCC). First-line therapy was determined by the treating physicians: 25 patients received immunosuppressive therapy (IST), 12 patients received haematopoietic stem cell transplantation (HSCT) and one patient received intensive chemotherapy. The remaining 27 patients were followed without treatment for more than 2 years (watch and wait; WW). In the WW group, 18 patients had stable disease without further intervention. Thirteen of 29 patients (45%) who ended up receiving IST showed response. The combination of ciclosporin and antithymocyte globulin was not shown to be superior to ciclosporin alone with regard to response rate or survival. Of 28 patients who ended up undergoing HSCT, 17 patients are alive in complete remission, whereas nine patients died mostly due to transplantation-related mortality. The 5-year overall survival for all patients was 82 +/- 5%. Eight patients suffered from disease progression. Patients with monosomy 7 or multilineage-dysplasia had a significantly higher incidence of disease progression. This analysis revealed heterogeneity in the clinical course of RCC, varying from those who remained stable for long periods to those who progressed to advanced disease.

Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification.
Daisuke Hasegawa, Xiaojuan Chen, Shinsuke Hirabayashi, Yasushi Ishida, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Atsuko Masunaga, Ayami Yoshimi, Asahito Hama, Seiji Kojima, Masafumi Ito, Tatsutoshi Nakahata, Atsushi Manabe
British journal of haematology, 166, 5, 758, 66, 2014年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, This study analysed 65 children who were prospectively registered between 1999 and 2008 and fulfilled the World Health Organization 2008 criteria of refractory cytopenia of childhood (RCC). First-line therapy was determined by the treating physicians: 25 patients received immunosuppressive therapy (IST), 12 patients received haematopoietic stem cell transplantation (HSCT) and one patient received intensive chemotherapy. The remaining 27 patients were followed without treatment for more than 2 years (watch and wait; WW). In the WW group, 18 patients had stable disease without further intervention. Thirteen of 29 patients (45%) who ended up receiving IST showed response. The combination of ciclosporin and antithymocyte globulin was not shown to be superior to ciclosporin alone with regard to response rate or survival. Of 28 patients who ended up undergoing HSCT, 17 patients are alive in complete remission, whereas nine patients died mostly due to transplantation-related mortality. The 5-year overall survival for all patients was 82 ± 5%. Eight patients suffered from disease progression. Patients with monosomy 7 or multilineage-dysplasia had a significantly higher incidence of disease progression. This analysis revealed heterogeneity in the clinical course of RCC, varying from those who remained stable for long periods to those who progressed to advanced disease.

Treatment outcomes of adolescent acute lymphoblastic leukemia treated on Tokyo Children's Cancer Study Group (TCCSG) clinical trials
Motohiro Kato, Atsushi Manabe, Katsuyoshi Koh, Takeshi Inukai, Nobutaka Kiyokawa, Takashi Fukushima, Hiroaki Goto, Daisuke Hasegawa, Chitose Ogawa, Kazutoshi Koike, Setsuo Ota, Yasushi Noguchi, Akira Kikuchi, Masahiro Tsuchida, Akira Ohara
INTERNATIONAL JOURNAL OF HEMATOLOGY, 100, 2, 180, 187, SPRINGER JAPAN KK, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）, There is no standard treatment for adolescents aged 15 years or older with acute lymphoblastic leukemia (ALL), although this age group has been reported as having a poorer prognosis compared to younger patients. We retrospectively analyzed the outcomes of three consecutive Tokyo Children's Cancer Study Group ALL trials (1995-2006) of 373 patients aged 10 years or older, with particular focus on adolescents aged 15-18 years (older-adolescents n = 41), compared to those aged 10-14 years (younger-adolescents n = 332). The probability of event-free survival at 8 years was 67.5 +/- A 7.4 % for the older-adolescents and 66.5 +/- A 2.6 % for the younger-adolescents (p = 0.95). Overall survival was 70.7 +/- A 7.1 % for the older-adolescents and 74.3 +/- A 2.4 % for the younger-adolescents (p = 0.48). The differences between groups in relapse incidence, non-relapse mortality, and death rate during induction were not statistically significant, although the older-adolescents trended towards a higher frequency of having stem-cell transplantation during the first remission. In conclusion, our treatment strategy, which consists of intensive induction and block-type consolidation, provided improved outcomes for patients aged 15-18 years, comparable to those for patients aged 10-14 years.

Prognostic impact of gained chromosomes in high-hyperdiploid childhood acute lymphoblastic leukaemia: a collaborative retrospective study of the Tokyo Children's Cancer Study Group and Japan Association of Childhood Leukaemia Study
Motohiro Kato, Toshihiko Imamura, Atsushi Manabe, Yoshiko Hashii, Katsuyoshi Koh, Atsushi Sato, Hiroyuki Takahashi, Hiroki Hori, Tomohiko Taki, Masami Inoue, Yasuhide Hayashi, Keizo Horibe, Masahiro Tsuchida, Seiji Kojima, Megumi Oda, Akira Ohara
BRITISH JOURNAL OF HAEMATOLOGY, 166, 2, 295, 298, WILEY-BLACKWELL, 2014年07月, ［査読有り］
英語

Clinicians' perspectives on support for children with a parent who is diagnosed with breast cancer
Yuko Takei, Miwa Ozawa, Yasushi Ishida, Shin-ichi Suzuki, Shinji Ohno, Atsushi Manabe
BREAST CANCER, 21, 4, 463, 471, SPRINGER JAPAN KK, 2014年07月, ［査読有り］
英語, 研究論文（学術雑誌）, There are few data on clinicians' perspectives regarding support for children who have a parent who has been diagnosed with breast cancer. The purpose of this study was to survey the attitudes of physicians and nurses regarding the care of children who had a parent diagnosed with breast cancer.
A survey was mailed to 898 physicians and 135 nurses who were members of the Japanese Breast Cancer Society in 2009. They were asked to answer questions about their attitudes toward and current practice regarding care for children who had a parent with breast cancer.
A total of 340 surveys (284 physicians and 56 nurses) were used in this analysis. The mean age of the respondents was 47.2 years, and their mean number of years of practice was 21.7 years. While 69.1 % of them reported that they felt it important for people in their roles to provide support for children, 84.4 % felt they could not provide sufficient support. The results also suggested that female gender in practitioners and nurses as opposed to doctor status seemed to be associated with preference for intervention, current practice of intervention, and recognition of difficulty to support.
Physicians and nurses express a variety of opinions with regard to support for children with a parent who has breast cancer. It is important to cooperate with other specialists including physicians, nurses, and psychologists and allocate roles appropriately among them to improve outcomes for these children.

Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia who developed blast crisis: MDS Committee of Japanese Society of Paediatric Haematology/Oncology
Yuko Honda, Masahiro Tsuchida, Yuji Zaike, Atsuko Masunaga, Ayami Yoshimi, Seiji Kojima, Masafumi Ito, Akira Kikuchi, Tatsutoshi Nakahata, Atsushi Manabe
BRITISH JOURNAL OF HAEMATOLOGY, 165, 5, 682, 687, WILEY-BLACKWELL, 2014年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukaemia (JMML) is a rare haematopoietic stem cell disease of early childhood, which can progress to blast crisis in some children. A total of 153 children diagnosed with JMML were reported to the Myelodysplastic Syndrome Committee in Japan between 1989 and 2007; 15 of them (9<bold>8</bold>%) had 20% or more blasts in the bone marrow (blast crisis) during the disease course. Blast crisis occurred during observation without therapy (n=3) or with oral 6-mercaptopurine treatment (n=9) and in relapse after haematopoietic stem cell transplantation (HSCT; n=3). Six patients had a complex karyotype (5 including monosomy 7) and an additional three patients had isolated monosomy 7 at blast crisis. Seven patients received HSCT after blast crisis and four of them achieved remission. Eleven out of the 15 patients died; the cause of death was disease progression in 10 patients and transplant-related complication in one patient. In summary, patients with blast crisis have poor prognosis and can be cured only by HSCT. The emergence of monosomy 7 and complex karyotype may be characteristic of blast crisis in a substantial subset of children.

Methylenetetrahydrofolate reductase gene haplotypes affect toxicity during maintenance therapy for childhood acute lymphoblastic leukemia in Japanese patients
Yoichi Tanaka, Atsushi Manabe, Hisaya Nakadate, Kensuke Kondoh, Kozue Nakamura, Katsuyoshi Koh, Akira Kikuchi, Takako Komiyama
LEUKEMIA & LYMPHOMA, 55, 5, 1126, 1131, INFORMA HEALTHCARE, 2014年05月, ［査読有り］
英語, 研究論文（学術雑誌）, The aim of this study was to investigate the influence of daily 6-mercaptopurine (6-MP) and low-dose weekly methotrexate (MTX) combination treatment and methylenetetrahydrofolate reductase (MTHFR) haplotypes on toxicity during maintenance therapy in Japanese childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed the MTHFR C677T and A1298C polymorphisms and influence of haplotypes on toxicity in 73 patients. Patients with the MTHFR 677TT and 677CT + 1298AC were associated with severe liver toxicity (p = 0.014, odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.27-11.46) and more rapid onset of liver toxicity (p = 0.010). Patients with MTHFR 677TT and 677CT + 1298AC were associated with lower frequency of 6-MP and MTX dose reduction due to leukopenia (p < 0.05). No difference was observed in average drug doses in the MTHFR genotypes. In conclusion, the MTHFR C677T and A1298C haplotypes might be useful for monitoring adverse effects in childhood ALL maintenance therapy in Japanese patients.

【血管腫・血管奇形2014:診断からIVR・治療まで】画像診断
野崎 太希, 松迫 正樹, 衛藤 光, 松井 瑞子, 新見 康成, 真部 淳, 草川 功, 鈴木 高祐, 栗原 泰之
臨床画像, 30, 5, 492, 504, (株)メジカルビュー社, 2014年05月
日本語

Parents’ perception of pediatric cancer centers in Japan.
Sakaguchi S, Oda M, Shinkoda Y, Manabe A
Pediatrics international : official journal of the Japan Pediatric Society, 56, 2, 196, 199, WILEY-BLACKWELL, 2014年04月, ［査読有り］
英語, 研究論文（学術雑誌）, BackgroundIn Japan, more than 160 hospitals provide care for approximately 2500 pediatric patients diagnosed with cancer each year. Not all hospitals, however, are fully capable of providing state-of-the-art care due to a lack of experienced personnel or up-to-date facilities. The aim of this study was to solicit parents' experiences during their children's cancer treatment and opinions about the centralization of medical resources to core pediatric cancer centers.
MethodsA structured questionnaire was sent to parents of children who had received cancer treatment.
ResultsEighty-two questionnaires were completed and analyzed. Parents reported a need for improved psychological support for their children and family members as well as accommodation for families during cancer therapy. Most parents had positive opinions about the centralization of medical resources to core centers but were concerned about the accessibility of the centers and increasing burdens placed on families living in remote areas.
ConclusionThe demand for psychological care for families during children's cancer treatment is highlighted. Improved accommodation and greater financial and social support for families living in remote areas should be preconditions for the future centralization of core pediatric cancer centers.

Allogeneic stem cell transplantation for patients with acute myeloid leukaemia developing from severe congenital neutropenia
Yasuhiro Ebihara, Kumiko Ishikawa, Shinji Mochizuki, Ryuhei Tanaka, Atsushi Manabe, Tohru Iseki, Taira Maekawa, Kohichiro Tsuji
BRITISH JOURNAL OF HAEMATOLOGY, 164, 3, 459, 461, WILEY-BLACKWELL, 2014年02月, ［査読有り］
英語

No impact of high-dose cytarabine and asparaginase as early intensification with intermediate-risk paediatric acute lymphoblastic leukaemia: results of randomized trial TCCSG study L99-15
Motohiro Kato, Katsuyoshi Koh, Atsushi Manabe, Tomohiro Saito, Daisuke Hasegawa, Keiichi Isoyama, Akitoshi Kinoshita, Miho Maeda, Yuri Okimoto, Michiko Kajiwara, Takashi Kaneko, Kanji Sugita, Akira Kikuchi, Masahiro Tsuchida, Akira Ohara
BRITISH JOURNAL OF HAEMATOLOGY, 164, 3, 376, 383, WILEY-BLACKWELL, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）, The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n=156) or standard early intensification including standard-dose cytarabine arm (n=154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8years in the experimental and standard arms were 723 +/- 37% and 775 +/- 35%, respectively (P=032). The 8-year overall survival rates for these two arms were 850 +/- 30% and 869 +/- 28%, respectively (P=072). The frequency of infectious events was significantly higher in the experimental arm (664%) than in the standard arm (246%) (P<0001). In conclusion, experimental early intensification including high-dose cytarabine followed by L-asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.

蛋白漏出性胃腸症で発症したHenoch-Schoenlein紫斑病の一例　　　　　　　　　　　　　　　
孫 楽, 吉本 優里, 小野 林太郎, 長谷川 大輔, 小澤 美和, 真部 淳, 草川 功
日本小児科学会雑誌, 118, 2, 398, 398, (公社)日本小児科学会, 2014年02月
日本語

熱性痙攣に対する抗ヒスタミン薬の影響についての検討　　　　　　　　　　　　　　　
辻本 信一, 吉本 優里, 小野 林太郎, 小澤 美和, 真部 淳, 草川 功, 石田 也寸志, 荻原 正明
日本小児科学会雑誌, 118, 2, 230, 230, (公社)日本小児科学会, 2014年02月
日本語

Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group
Trudy D. Buitenkamp, Shai Izraeli, Martin Zimmermann, Erik Forestier, Nyla A. Heerema, Marry M. van den Heuvel-Eibrink, Rob Pieters, Carin M. Korbijn, Lewis B. Silverman, Kjeld Schmiegelow, Der-Cheng Liang, Keizo Horibe, Maurizio Arico, Andrea Biondi, Giuseppe Basso, Karin R. Rabin, Martin Schrappe, Gunnar Cario, Georg Mann, Maria Morak, Renate Panzer-Grumayer, Veerle Mondelaers, Tim Lammens, Helene Cave, Batia Stark, Ithamar Ganmore, Anthony V. Moorman, Ajay Vora, Stephen P. Hunger, Ching-Hon Pui, Charles G. Mullighan, Atsushi Manabe, Gabriele Escherich, Jerzy R. Kowalczyk, James A. Whitlock, C. Michel Zwaan
BLOOD, 123, 1, 70, 77, AMER SOC HEMATOLOGY, 2014年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- < 1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 x 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups.

血液検査所見が正常で骨病変にて発見されたB前駆細胞性急性リンパ性白血病(ALL)の1例　　　　　　　　　　　　　　　
原 朋子, 長谷川 大輔, 小野 林太郎, 居石 崇志, 吉本 優里, 上野 浩生, 細谷 要介, 吉原 宏樹, 真部 淳
日本小児科学会雑誌, 118, 1, 77, 77, (公社)日本小児科学会, 2014年01月
日本語

Significance of CD66c expression in childhood acute lymphoblastic leukemia
Nobutaka Kiyokawa, Kazutoshi Iijima, Osamu Tomita, Masashi Miharu, Daisuke Hasegawa, Kenichiro Kobayashi, Hajime Okita, Michiko Kajiwara, Hiroyuki Shimada, Takeshi Inukai, Atsushi Makimoto, Toru Nanmoku, Katsuyoshi Koh, Atsushi Manabe, Akira Kikuchi, Junichiro Fujimoto, Yasuhicie Hayashi, Akira Ohara
LEUKEMIA RESEARCH, 38, 1, 42, 48, PERGAMON-ELSEVIER SCIENCE LTD, 2014年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Upon analyze in 695 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases, we identified the characteristics of CD36c expression. In addition to the confirmation of wrong correlation with BCR-ABL positivity and hyperdiploid, we further observed that CD66c is frequently expressed in CRLF2-positive (11/15, p < 0.01 against chiineric gene-negative foss ell as hypediploid cases (314 whereas Sic never expressed in ETVA-RUNX1 MLL-AF4, MLL-AF9, MLL-ENL, and E2A-PBX1-positive cases, Although the expression CD66c itself is not directly linked to the prognosis, the accompanying genetic abnormalities are important prognostic factors for BC P-ALL indicating the importance of CD66c expression in the initial diagnosis of BCP-ALL. (C) 2013 Elsevier Ltd. All rights reserved.

Significance of CD66c expression in childhood acute lymphoblastic leukemia
Nobutaka Kiyokawa, Kazutoshi Iijima, Osamu Tomita, Masashi Miharu, Daisuke Hasegawa, Kenichiro Kobayashi, Hajime Okita, Michiko Kajiwara, Hiroyuki Shimada, Takeshi Inukai, Atsushi Makimoto, Takashi Fukushima, Toru Nanmoku, Katsuyoshi Koh, Atsushi Manabe, Akira Kikuchi, Kanji Sugita, Junichiro Fujimoto, Yasuhide Hayashi, Akira Ohara
Leukemia Research, 38, 1, 42, 48, 2014年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Upon analyzing 696 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases, we identified the characteristics of CD66c expression. In addition to the confirmation of strong correlation with BCR-ABL positivity and hyperdiploid, we further observed that CD66c is frequently expressed in CRLF2-positive (11/15, p <
0.01 against chimeric gene-negative) as well as hypodiploid cases (3/4), whereas it is never expressed in ETV6-RUNX1, MLL-AF4, MLL-AF9, MLL-ENL, and E2A-PBX1-positive cases. Although the expression of CD66c itself is not directly linked to the prognosis, the accompanying genetic abnormalities are important prognostic factors for BCP-ALL, indicating the importance of CD66c expression in the initial diagnosis of BCP-ALL. © 2013 Elsevier Ltd.

Imaging of vascular tumors with an emphasis on ISSVA classification
Taiki Nozaki, Masaki Matsusako, Hidefumi Mimura, Keigo Osuga, Mizuko Matsui, Hikaru Eto, Naoyuki Ohtake, Atsushi Manabe, Isao Kusakawa, Yoshiyuki Tsutsumi, Shunsuke Nosaka, Minobu Kamo, Yukihisa Saida
JAPANESE JOURNAL OF RADIOLOGY, 31, 12, 775, 785, SPRINGER, 2013年12月, ［査読有り］
英語, 研究論文（学術雑誌）, The International Society for the Study of Vascular Anomalies (ISSVA) classification is becoming the international standard classification system for vascular tumors and vascular malformations. The ISSVA classification strictly distinguishes vascular tumors (neoplastic lesions) from vascular malformations (non-neoplastic lesions) based on whether there is a proliferation of vascular endothelial cells present, and it is an extremely useful classification system for determining therapeutic measures. For vascular tumors, it is clinically significant in terms of discriminating infantile hemangioma and rapidly involuting congenital hemangioma, which are expected to spontaneously regress, from other vascular tumors requiring treatment. Needless to say, clinical courses are important for diagnosis, and it is also important for radiologists to understand imaging findings on vascular tumors because such tumors have unique findings on diagnostic images. In this paper, vascular tumors are classified based on the ISSVA classification, and clinical and imaging findings are reviewed.

【小児の痛みについて考える】小児の疼痛の緩和 小児がん性疼痛治療
小澤 美和, 真部 淳
小児科臨床, 66, 12, 2541, 2547, (株)日本小児医事出版社, 2013年12月
日本語

Significance Of Minimal Residual Disease Detected By Multi-Color Flow Cytometry In Childhood Acute Myeloid Leukemia With The Intermideate-Risk Cytogenetics and Negative FMS-Like Tyrosine Kinase 3 Internal Tandem Duplication: A Report Of The Tokyo Children's Cancer Study Group
Dai Keino, Akitoshi Kinoshita, Daisuke Tomizawa, Hiroyuki Takahashi, Kohmei Ida, Hidemitsu Kurosawa, Kazutoshi Koike, Setsuo Ota, Noriyuki Iwasaki, Junya Fujimura, Yuki Yuza, Chikako Kiyotani, Shohei Yamamoto, Tomoo Osumi, Takahiro Ueda, Shinji Mochizuki, Keiichi Isoyama, Ryoji Hanada, Akio Tawa, Akira Kikuchi, Atsushi Manabe, Akira Ohara
Blood, 122, 21, 1416, 1416, American Society of Hematology, 2013年11月15日
研究論文（学術雑誌）, Abstract

Background

Response to induction chemotherapy is one of the most important predictors of outcome in acute myeloid leukemia (AML) as well as cytogenetics and molecular genetics. Measurement of minimal residual disease (MRD) by flow cytometry is an informative method for assessment of initial treatment response, but the heterogeneity of leukemia-associated antigens and antigen shifts during treatment limit its sensitivity and specificity. We prospectively evaluated the prognostic prevalence of MRD monitoring using multi-color flow cytometry in children with AML treated on the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 trial.

Patients and methods

From January 2007 to October 2010, 34 children with newly diagnosed de novo AML were enrolled on the AML-MRD study conducted by the Tokyo Children's Cancer Study Group. The median age at the diagnosis was 8 years (1 month- 15 years), and 17 patients were boys and 17 were girls. They were all treated with the JPLSG AML-05 trial. In AML-05, enrolled patients received two induction courses and those achieving a complete remission (CR) were treated according to risk classification at which all the core binding factor-AML cases and good initial response based on morphology after induction 1 were assigned to low risk (LR) group, cases presented with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), unfavorable cytogenetics including monosomy7, 5q-,t(16;21), and with poor initial response were assigned to high risk (HR) group, the others were assigned to intermediate risk (IR) group. Allogeneic hematopoietic stem cell transplantation (HSCT) was indicated for the HR patients after the third or later treatment courses. Among the 34 patients enrolled on the AML-MRD study, 8 presented with LR, 22 with IR, and 4 with HR regarding the cytogenetics and FLT3-ITD status. MRD of 63 bone marrow samples were analyzed after induction 1 (BMA-2) and induction 2 (BMA-3) by four-color flow cytometry using 9 AML-associated antigens. A threshold level for MRD-positivity was set at the point of 0.1%.

Results

Sixty-two (98.4%) of 63 bone marrow samples were evaluable for MRD. Thirteen (39.4%) of 33 samples and 8 (27.6%) of 29 showed MRD-positivity at BMA-2 and BMA-3 respectively. Among the patients with MRD-positivity, 12 at BMA-2 and 7 at BMA-3 were diagnosed as achieving CR by morphology. MRD was associated neither specific FAB subtype nor white blood cell count at diagnosis, but all 3 patients with FLT3-ITD showed the MRD-positivity at BMA-2. Although 3-year probability of event free survival (3-yr EFS) at BMA-2 or BMA-3 was similar between patients with and without MRD; 53.8% (n= 13) vs 70.0% (n= 20) (p=0.30) and 50.0% (n= 8)vs 62.0%(n= 21) (p=0.36), respectively, 3-yr EFS of those with MRD at BMA-2 or BMA-3 was significantly worse compared to those without MRD; 33.3% (n= 9) vs 83.3% (n= 12) (p=0.02) and 20.0%(n= 5) vs 76.9% (n= 13) (p=0.04), respectively, in the group of the IR cytogenetics and negative FLT3-ITD. Multivariate analysis indicated that the MRD detected by multi-color flow cytometry was solely associated with worse outcome in this group.

Conclusion

Highly sensitive detection of MRD by multi-color flow cytometry was possible in children with AML. The present study suggests that MRD monitoring may have a prognostic relevance in childhood AML with the IR cytogenetics and negative FLT3-ITD.

Disclosures:

No relevant conflicts of interest to declare.

骨病変が先行して発症した急性リンパ性白血病の4例　　　　　　　　　　　　　　　
原 朋子, 長谷川 大輔, 野崎 太希, 小野 林太郎, 吉本 優里, 上野 浩生, 細谷 要介, 吉原 宏樹, 熊本 忠志, 細谷 亮太, 真部 淳
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 284, 284, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

MDSに血球貪食症候群を合併し、移植後自己造血回復状態となるも異常クローンを認めず経過観察している1例　　　　　　　　　　　　　　　
上野 浩生, 石田 悠志, 小野 林太郎, 吉本 優里, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 大島 久美, 熊本 忠史, 森 慎一郎, 細谷 亮太, 真部 淳
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 328, 328, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

初期治療反応性が不良で早期再発を来したDown症候群合併急性巨核芽球性白血病(DS-AMKL)例　　　　　　　　　　　　　　　
吉本 優里, 小野 林太郎, 上野 浩生, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 小澤 美和, 熊本 忠史, 森 愼一郎, 澤田 明久, 井上 雅美, 細谷 亮太, 真部 淳
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 249, 249, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

Ultra low-dose cytarabine(Ara-C)療法で寛解を維持しているDown症合併急性巨核芽球性白血病(DS-AMKL)の一例　　　　　　　　　　　　　　　
吉本 優里, 吉原 宏樹, 小野 林太郎, 上野 浩生, 細谷 要介, 長谷川 大輔, 熊本 忠史, 小澤 美和, 岩本 彰太郎, 盛武 浩, 細谷 亮太, 真部 淳
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 249, 249, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

寛解状態にある小児がん患者の退院後の生活を支えるソーシャルサポートの特徴　　　　　　　　　　　　　　　
武井 優子, 小澤 美和, 盛武 浩, 真部 淳, 鈴木 伸一
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 310, 310, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

終末期の子どもをケアする医療者へのグリーフケアの検討　　　　　　　　　　　　　　　
鳥山 祐子, 齊藤 由華, 小川 恵里子, 植松 温子, 清藤 育子, 高嶋 希世子, 西野 理英, 関冨 晶子, 吉原 宏樹, 小澤 美和, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 374, 374, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

ダウン症児の受容過程について理解し合えなかった両親が、白血病で子どもを亡くした後にむかえた夫婦の危機　　　　　　　　　　　　　　　
清藤 育子, 植松 温子, 小川 恵理子, 鳥山 裕子, 上野 浩生, 長谷川 大輔, 細谷 要介, 小澤 美和, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 383, 383, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2013年11月
日本語

A review series begins: How much do we know about intractable disease?
Atsushi Manabe
PEDIATRICS INTERNATIONAL, 55, 5, 541, 541, WILEY-BLACKWELL, 2013年10月, ［査読有り］
英語

[Molecular biology in childhood acute lymphoblastic leukemia (ALL)].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 54, 10, 1999, 2005, The Japanese Society of Hematology, 2013年10月, ［査読有り］
日本語

小児白血病MRD検出における10カラーフローサイトメトリーの有用性
三春 晶嗣, 清河 信敬, 小林 健一郎, 大喜多 肇, 飯島 一智, 森 鉄也, 斎藤 正博, 福島 敬, 康 勝好, 真部 淳, 菊地 陽, 林 泰秀, 小原 明
Cytometry research : 日本サイトメトリー学会機関誌, 23, 2, 7, 14, 日本サイトメトリー学会, 2013年09月25日
日本語,

In childhood acute lymphoblastic leukemia (ALL), the clinical significance of minimal residual disease (MRD) has been demonstrated. Polymerase chain reaction assays based on the detection of clonal rearrangement of immunoglobulin and T-cell receptor genes are most established method for MRD analysis. However, the flow cytometric detection of MRD also has advantages in simplicity of the method as well as a low-cost, high-performance. Conventionally, 3 or 4 color analysis employing multiple test tubes of the panel of antibodies is used for the detection of leukemia-associated immunophenotypes, whereas we developed 10 color methods of MRD detection for both BCP-ALL and T-ALL. Our methods are able to take effect easily and exhibit high performance. To put it to practical use, further investigations are now underway.

オーバービュー
真部 淳
臨床血液, 54, 8, 719, 720, The Japanese Society of Hematology, 2013年08月30日
日本語

[What we can learn from childhood leukemology: focusing on ALL].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 54, 8, 744, 748, The Japanese Society of Hematology, 2013年08月, ［査読有り］
日本語

[Retrospective analysis of treatment strategy and prognosis in childhood myelodysplastic syndromes from China and Japan].
Chen XJ, Manabe A, Yang WY, Zhang PH, Wang SC, Guo Y, Liu F, Chang LX, Wei W, Wan Y, Zhu XF
Zhongguo shi yan xue ye xue za zhi, 21, 4, 940, 947, 2013年08月, ［査読有り］

[Information on pediatric hematology necessary for hematology internists. Overview].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 54, 8, 719, 720, 2013年08月, ［査読有り］

Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology
Keizo Horibe, Akiko M. Saito, Tetsuya Takimoto, Masahiro Tsuchida, Atsushi Manabe, Midori Shima, Akira Ohara, Shuki Mizutani
INTERNATIONAL JOURNAL OF HEMATOLOGY, 98, 1, 74, 88, SPRINGER JAPAN KK, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Neither accurate incidence nor survival data for pediatric patients with hematological malignancies (HM) have been available in Japan to date. Incidence of patients under 20 years of age, who were diagnosed with HM from 2006 to 2010, and their two-year survival rate (2y-OS) were obtained from disease registry data maintained by the Japan Society of Pediatric Hematology (JSPH). A total of 5,287 cases of HM were identified during this period. Acute lymphoblastic leukemia (ALL, 46.6 %) showed the highest incidence, followed by acute myeloid leukemia (AML, 16.7 %), non-Hodgkin lymphoma (NHL, 11.9 %), and histiocytosis (11.8 %). ALL, AML and histiocytosis were common in younger patients aged 1-4, while NHL tended to occur more frequently in older patients aged 5-14. The 2y-OS of HM was 91.6 %, with that for the most common B-precursor ALL rising to 96.2 %. The 2y-OS for M3 AML, lymphoblastic-B-precursor or diffuse large B cell NHL, Hodgkin lymphoma, myeloproliferative disorders, and Langerhans cell histiocytosis was > 95 %. There were no gender differences in prognosis, while infants (88.0 %) and adolescents aged 15-19 (90.6 %) tended toward a poorer prognosis. This is the first report to describe incidence and survival times from the nationwide JSPH disease registry. More precise data with longer follow-up is needed.

Temporal Lobe Epilepsy With Hippocampal Sclerosis in Acute Lymphoblastic Leukemia
Emi Kasai-Yoshida, Masaaki Ogihara, Miwa Ozawa, Taiki Nozaki, Michiharu Morino, Atsushi Manabe, Ryota Hosoya
PEDIATRICS, 132, 1, E252, E256, AMER ACAD PEDIATRICS, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

Li Fraumeni症候群に発症したGlioblastomaの1男児例
上野 浩生, 小野 林太郎, 吉本 優里, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 熊本 忠史, 真部 淳, 細谷 亮太, 野崎 太希, 萩原 英樹, 師田 信人
日本小児血液・がん学会雑誌, 50, 2, 284, 284, (一社)日本小児血液・がん学会, 2013年07月
日本語

Aggressive Transformation of Juvenile Myelomonocytic Leukemia Associated with Duplication of Oncogenic KRAS due to Acquired Uniparental Disomy
Motohiro Kato, Naoko Yasui, Masafumi Seki, Hiroshi Kishimoto, Aiko Sato-Otsubo, Daisuke Hasegawa, Nobutaka Kiyokawa, Ryoji Hanada, Seishi Ogawa, Atsushi Manabe, Junko Takita, Katsuyoshi Koh
JOURNAL OF PEDIATRICS, 162, 6, 1285, +, MOSBY-ELSEVIER, 2013年06月, ［査読有り］
英語, 研究論文（学術雑誌）, A small fraction of cases of juvenile myelomonocytic leukemia (JMML) develop massive disease activation. Through genomic analysis of JMML, which developed in an individual with mosaicism for oncogenic KRAS mutation with rapid progression, we identified acquired uniparental disomy at 12p. We demonstrated that duplication of oncogenic KRAS is associated with rapid JMML progression.

Magnetic resonance imaging appearance of primary spinal extradural Ewing's sarcoma: Case report and literature review
S. Tsutsumi, Y. Yasumoto, A. Manabe, I. Ogino, H. Arai, M. Ito
Clinical Neuroradiology, 23, 2, 81, 85, 2013年06月, ［査読有り］
英語, 研究論文（国際会議プロシーディングス）, Purpose: Primary spinal extradural Ewing's sarcoma (PSEES) or primitive neuroectodermal tumor (PNET) is uncommon. The present study summarizes the magnetic resonance (MR) imaging appearance of PSEES. Methods: Literature search from 1994 to 2012 with our representative case presentation. Results: Twenty-one patients, 12 males and 9 females, aged 3 weeks to 44 years, were identified. The thoracic spine was most frequently affected, followed by the cervical, cervicothoracic, and thoracolumbar spine. Superior-inferior extension of lesions was three vertebral levels in 7, two in 7, five in 4, four in 1, one in 1 and unknown in 1. PSEESs appeared isointense in 9 cases, hypointense in 2, hyperintense in 1, and no description in 9 on T1-weighted imaging, while hyperintense in 6, hypointense in 3, heterogeneous in 1, and no description in 11 on T2-weighted imaging. Varying enhancement was noted in 13 cases (62 %), with no description of contrast study in the other 8 cases. Dumbbell-shaped configuration of PSEES was found in 5 cases, foraminal widening in 4, and erosions or scalloping of the adjacent vertebral bodies in 4. Conclusion: The MR imaging appearance of PSEESs is indistinguishable from other tumors. PSEES should be assumed as the differential diagnosis of spinal extradural tumors in pediatric, adolescent, and young adult patients, and prompt surgical exploration should be performed. © 2013 Springer-Verlag Berlin Heidelberg.

IDEAL‐IQで鉄含有量の半定量化を試みたヘモクロマトーシスの3例
森田有香, 野崎太希, 小野林太郎, 長谷川大輔, 吉原宏樹, 細谷要介, 真部淳, 齋田幸久
日本小児放射線学会雑誌, 29, 20, 2013年05月20日
日本語

Association between parental preference and head computed tomography in children with minor blunt head trauma.
Yasushi Ishida, Atsushi Manabe, Aya Oizumi, Norio Otani, Michio Hirata, Kevin Urayama, Yukihisa Saida, Isao Kusakawa, Tsuguya Fukui
JAMA pediatrics, 167, 5, 491, 2, 2013年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

WiskottAldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia
Ayami Yoshimi, Yoshiro Kamachi, Kosuke Imai, Nobuhiro Watanabe, Hisaya Nakadate, Takashi Kanazawa, Shuichi Ozono, Ryoji Kobayashi, Misa Yoshida, Chie Kobayashi, Asahito Hama, Hideki Muramatsu, Yoji Sasahara, Marcus Jakob, Tomohiro Morio, Stephan Ehl, Atsushi Manabe, Charlotte Niemeyer, Seiji Kojima
PEDIATRIC BLOOD & CANCER, 60, 5, 836, 841, WILEY-BLACKWELL, 2013年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Background WiskottAldrich syndrome (WAS) is a rare X-linked immunodeficiency caused by defects of the WAS protein (WASP) gene. Patients with WAS typically demonstrate micro-thrombocytopenia. Procedures The report describes seven male infants with WAS that initially presented with leukocytosis, monocytosis, and myeloid and erythroid precursors in the peripheral blood (PB) and dysplasia in the bone marrow (BM), which was initially indistinguishable from juvenile myelomonocytic leukaemia (JMML). Results The median age of affected patients was 1 month (range, 14 months). Splenomegaly was absent in four of these patients, which was unusual for JMML. A mutation analysis of genes in the RAS-signalling pathway did not support a diagnosis of JMML. Non-haematological features, such as eczema (n=7) and bloody stools (n=6), ultimately led to the diagnosis of WAS at a median age of 4 months (range, 38 months), which was confirmed by absent (n=6) or reduced (n=1) WASP expression in lymphocytes by flow cytometry (FCM) and a WASP gene mutation. Interestingly, mean platelet volume (MPV) was normal in three of five patients and six of seven patients demonstrated occasional giant platelets, which was not compatible with WAS. Conclusions These data suggest that WAS should be considered in male infants presenting with JMML-like features if no molecular markers of JMML can be detected. Pediatr Blood Cancer 2013; 60: 836841. (c) 2012 Wiley Periodicals, Inc.

Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia
Ayami Yoshimi, Yoshiro Kamachi, Kosuke Imai, Nobuhiro Watanabe, Hisaya Nakadate, Takashi Kanazawa, Shuichi Ozono, Ryoji Kobayashi, Misa Yoshida, Chie Kobayashi, Asahito Hama, Hideki Muramatsu, Yoji Sasahara, Marcus Jakob, Tomohiro Morio, Stephan Ehl, Atsushi Manabe, Charlotte Niemeyer, Seiji Kojima
Pediatric Blood and Cancer, 60, 5, 836, 841, 2013年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency caused by defects of the WAS protein (WASP) gene. Patients with WAS typically demonstrate micro-thrombocytopenia. Procedures: The report describes seven male infants with WAS that initially presented with leukocytosis, monocytosis, and myeloid and erythroid precursors in the peripheral blood (PB) and dysplasia in the bone marrow (BM), which was initially indistinguishable from juvenile myelomonocytic leukaemia (JMML). Results: The median age of affected patients was 1 month (range, 1-4 months). Splenomegaly was absent in four of these patients, which was unusual for JMML. A mutation analysis of genes in the RAS-signalling pathway did not support a diagnosis of JMML. Non-haematological features, such as eczema (n=7) and bloody stools (n=6), ultimately led to the diagnosis of WAS at a median age of 4 months (range, 3-8 months), which was confirmed by absent (n=6) or reduced (n=1) WASP expression in lymphocytes by flow cytometry (FCM) and a WASP gene mutation. Interestingly, mean platelet volume (MPV) was normal in three of five patients and six of seven patients demonstrated occasional giant platelets, which was not compatible with WAS. Conclusions: These data suggest that WAS should be considered in male infants presenting with JMML-like features if no molecular markers of JMML can be detected. © 2012 Wiley Periodicals, Inc.

[Current national and international status of supportive therapy for the coagulopathy associated with L-asparaginase containing regimen for acute lymphoblastic leukemia].
Ogawa C, Manabe A, Ohara A, Ishiguro A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 54, 3, 316, 318, The Japanese Society of Hematology, 2013年03月, ［査読有り］
日本語, We investigated supportive therapy against coagulopathy associated with L-asparaginase treatment in patients with acute lymphoblastic leukemia who were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG), Japan Adult Leukemia Study Group (JALSG), and foreign institutes. Fresh frozen plasma (FFP) was administered as a supplement in 46% patients in the JPLSG and 86% in the JALSG. The threshold level of FFP infusion was less than 100 mg/dl plasma fibrinogen in 70% of the JALSG and 20% of the JPLSG, while in another 20% of the JPLSG, FFP was administered when the fibrinogen level was less than 50 mg/dl. The preventive use of antithrombin products (AT) was prescribed in 93% of the JPLSG and 63% of the JALSG: The threshold level of AT supplementation was less than 70% of plasma antithrombin activity, which was similar in both groups. Most foreign institutes do not routinely use FFP or AT.

Resetting the course for Pediatrics International
Atsushi Manabe
PEDIATRICS INTERNATIONAL, 55, 1, 1, 1, WILEY-BLACKWELL, 2013年02月, ［査読有り］
英語

小児がん患者に併発したClostridium difficile腸炎の再発のリスク因子の検討　　　　　　　　　　　　　　　
吉原 宏樹, 代田 惇朗, 稲井 郁子, 小野 林太郎, 細谷 要介, 長谷川 大輔, 石田 也寸志, 真部 淳, 細谷 亮太
日本小児科学会雑誌, 117, 2, 345, 345, (公社)日本小児科学会, 2013年02月
日本語

小児慢性良性好中球減少症患者24名の臨床経過についての検討　　　　　　　　　　　　　　　
上野 浩生, 小野 林太郎, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 真部 淳, 細谷 亮太
日本小児科学会雑誌, 117, 2, 370, 370, (公社)日本小児科学会, 2013年02月
日本語

小児がん経験者の病気のとらえ方の特徴と退院後の生活における困難との関連
武井 優子, 尾形 明子, 小澤 美和, 盛武 浩, 平井 啓, 真部 淳, 鈴木 伸一
行動療法研究, 39, 1, 23, 33, 一般社団法人日本認知・行動療法学会, 2013年01月31日
日本語, 本研究の目的は、小児がん患者の病気に対するとらえ方の特徴と、それらが患者の心理社会的問題や適応とどのような関連があるのかを検討することであった。小児科外来通院中の21名の小児がん患者を対象に半構造化面接を実施し、病気に対するとらえ方と退院後の生活における困難について聴取した。また、健康関連QOL尺度(Peds-QL)を測定した。Fisherの直接確率検定の結果、退院後の生活で経験する困難が病気のとらえ方に影響を及ぼしている可能性が示唆された。また、重回帰分析の結果、前向きなとらえ方がQOLに正の影響を、後ろ向きなとらえ方やあきらめの姿勢が負の影響を及ぼす様相が示唆されたが、統計的には有意ではなかった。今後は、対象者数を増やし、量的検討を実施していく必要がある。

[Childhood acute lymphoblastic leukemia (ALL)].
Manabe A, Hasegawa D
[Rinsho ketsueki] The Japanese journal of clinical hematology, 54, 1, 100, 108, 2013年01月, ［査読有り］

Current evidence for an inherited genetic basis of childhood acute lymphoblastic leukemia
Kevin Y. Urayama, Anand P. Chokkalingam, Atsushi Manabe, Shuki Mizutani
INTERNATIONAL JOURNAL OF HEMATOLOGY, 97, 1, 3, 19, SPRINGER JAPAN KK, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and efforts to understand its etiology has followed a paradigm that common genetic variation in the presence of modifiable environmental factors contribute to disease risk. To date, there are numerous reports of candidate gene association studies suggesting an involvement of genetic loci in childhood ALL risk, but the general lack of consistency in results has underscored the need for careful interpretation and confirmation in additional well-designed studies. Complementary efforts using the genome-wide association study approach have shown indisputable evidence that common low penetrance genetic polymorphisms contribute to childhood ALL risk. However, current calculations show that these established disease loci only explain a portion of the total estimated contribution of common genetic variation on childhood ALL risk. Certain candidate gene loci previously examined likely contribute to this unexplained variation in risk, but the challenge moving forward will be to establish which ones based on the accumulating evidence. In this review, we describe the results of the most recent gene association studies in childhood ALL and discuss options for future efforts to advance this area of research.

Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS)
Rie Ohba, Kazumichi Furuyama, Kenichi Yoshida, Tohru Fujiwara, Noriko Fukuhara, Yasushi Onishi, Atsushi Manabe, Etsuro Ito, Keiya Ozawa, Seiji Kojima, Seishi Ogawa, Hideo Harigae
ANNALS OF HEMATOLOGY, 92, 1, 1, 9, SPRINGER, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. There are two forms of sideroblastic anemia, i.e., congenital sideroblastic anemia (CSA) and acquired sideroblastic anemia. In order to clarify the pathophysiology of sideroblastic anemia, a nationwide survey consisting of clinical and molecular genetic analysis was performed in Japan. As of January 31, 2012, data of 137 cases of sideroblastic anemia, including 72 cases of myelodysplastic syndrome (MDS)-refractory cytopenia with multilineage dysplasia (RCMD), 47 cases of MDS-refractory anemia with ring sideroblasts (RARS), and 18 cases of CSA, have been collected. Hemoglobin and MCV level in CSA are significantly lower than those of MDS, whereas serum iron level in CSA is significantly higher than those of MDS. Of 14 CSA for which DNA was available for genetic analysis, 10 cases were diagnosed as X-linked sideroblastic anemia due to ALAS2 gene mutation. The mutation of SF3B1 gene, which was frequently mutated in MDS-RS, was not detected in CSA patients. Together with the difference of clinical data, it is suggested that genetic background, which is responsible for the development of CSA, is different from that of MDS-RS.

小児急性リンパ性白血病の維持療法における副作用発現および投与量へのMRP4遺伝子多型の影響　　　　　　　　　　　　　　　
田中 庸一, 真部 淳, 中舘 尚也, 近藤 健介, 康 勝好, 中村 こずえ, 菊池 陽, 小宮山 貴子
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 287, 287, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

初発時に多発する頭蓋内出血を来したPh陽性急性リンパ性白血病の10歳女児の1例　　　　　　　　　　　　　　　
小野 林太郎, 長谷川 大輔, 石田 悠志, 細谷 要介, 吉原 宏樹, 熊本 忠史, 小川 千登世, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 320, 320, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

当院における小児がんの患児への告知に関する過去20年の検討　　　　　　　　　　　　　　　
吉本 優里, 上野 浩生, 吉原 宏樹, 細谷 要介, 長谷川 大輔, 小澤 美和, 石田 也寸志, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 267, 267, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

思春期患者のEnd-of-Lifeケアにおけるチーム医療の課題　　　　　　　　　　　　　　　
小川 恵理子, 植松 温子, 鳥山 祐子, 高嶋 希世子, 齋藤 由華, 清藤 育子, 西野 理英, 長谷川 大輔, 小澤 美和, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 307, 307, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

VDC/ICE療法及び放射線照射を行なった腎悪性ラブドイド腫瘍(MRTK)の一例　　　　　　　　　　　　　　　
辻本 信一, 上野 浩生, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 354, 354, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

高リスク神経芽腫に対するWT1ペプチドワクチン投与の経験　　　　　　　　　　　　　　　
細谷 要介, 吉原 宏樹, 長谷川 大輔, 西川 英里, 谷ヶ崎 博, 鈴木 涼子, 小林 千恵, 橋井 佳子, 杉山 治夫, 真部 淳, 細谷 亮太
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 408, 408, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

WT1ペプチドワクチンによる再発抑制効果を期待した小児悪性骨・軟部腫瘍対象多施設共同臨床試験　　　　　　　　　　　　　　　
橋井 佳子, 坪井 昭博, 尾路 祐介, 中島 博子, 岡 芳弘, 岩城 拓磨, 岩瀬 孝志, 細谷 要介, 真部 淳, 辻 尚子, 湯坐 有希, 杉山 治夫, 大薗 恵一
日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 426, 426, (NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 2012年11月
日本語

Outcome of children with refractory anaemia with excess of blast (RAEB) and RAEB in Transformation (RAEB-T) in the Japanese MDS99 study
Akira Kikuchi, Daisuke Hasegawa, Yoshitoshi Ohtsuka, Kazuko Hamamoto, Seiji Kojima, Jun Okamura, Tatsutoshi Nakahata, Atsushi Manabe
BRITISH JOURNAL OF HAEMATOLOGY, 158, 5, 657, 661, WILEY-BLACKWELL, 2012年09月, ［査読有り］
英語, 研究論文（学術雑誌）, We report the outcome of 16 children with refractory anaemia with excess of blasts (RAEB; n similar to=similar to 4) and RAEB in transformation (RAEB-T; n similar to=similar to 12) following induction therapy with etoposide, cytarabine and mitoxantrone (ECM) prior to haematopoietic stem cell transplantation (HSCT). The median observation period was 77 similar to months (range 5123). Complete remission rate was 81% following induction; no toxic deaths occurred. Eight-year event-free survival and overall survival was 50% and 56%, respectively. None of the three patients with a complex karyotype survived, suggesting karyotype is a crucial prognostic factor for survival. This study indicates the safety and high remission rate of ECM and high survival rates after HSCT for paediatric RAEB and RAEB-T.

[Molecular mechanism and treatment of juvenile myelomonocytic leukemia (JMML)].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 53, 8, 729, 733, 2012年08月, ［査読有り］

小児がん患者における病気のとらえ方の検討
武井 優子, 尾形 明子, 平井 啓, 小澤 美和, 盛武 浩, 真部 淳, 鈴木 伸一
心身医学, 52, 7, 638, 645, 日本心身医学会, 2012年07月01日
日本語, 本研究の目的は,小児がん患者の病気のとらえ方の特徴を明らかにすること,また,個人の属性によって病気のとらえ方に違いがみられるのかを検討することであった.小児科外来通院中の25名の小児がん患者を対象に半構造化面接を実施した結果,病気のとらえ方に関する11の構成要素が抽出された.また,患者の属性による違いを検討したところ,「視野,考え方が広がった」「人の痛みが分かるようになった」「貴重な体験だと思う」「病気になったのは仕方がない,諦めている」の4つの構成要素において,19歳以上の患者の方がそれ以外の年代の患者よりも回答頻度が高かった.これらの結果から,小児がん患者は,成長に伴い多角的なとらえ方をするようになることが示された.

Physician Preferences and Knowledge Regarding the Care of Childhood Cancer Survivors in Japan: A Mailed Survey of the Japanese Society of Pediatric Oncology
Yasushi Ishida, Miyako Takahashi, Mitsue Maru, Michiko Mori, Tara O. Henderson, Christopher K. Daugherty, Atsushi Manabe
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 42, 6, 513, 521, OXFORD UNIV PRESS, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Japanese physicians attitudes regarding the health-care needs of young adult childhood cancer survivors (CCSs) are not well described. Thus, we examined the self-reported preferences and knowledge of pediatric oncologists and surgeons.
A mailed survey was sent to 858 physician members of the Japanese Society of Pediatric Oncology. We compared the responses of pediatric oncologists and pediatric surgeons.
The pediatric oncologists response rate was 56 (300 out of 533) and that of pediatric surgeons 32 (105 out of 325). The median age of respondents was 46 and 48 years, respectively; 79 and 84 were men. When comfort levels in caring for CCSs were described (i.e. 1 very uncomfortable; 7 very comfortable), the mean levels were 4.4 and 3.8 with CCSs 21 years, 3.6 and 3.6 with 21 years CCSs 30 years, and 2.8 and 3.3 with CCSs 30 years, respectively. In clinical vignette questions, 62 of the pediatric oncologists and 43 of the surgeons answered three or more questions appropriately. Pediatric surgeons reported significantly lower familiarity with long-term follow-up guidelines than pediatric oncologists. Most pediatric oncologists and many surgeons conducted truth-telling of cancer diagnosis to adult CCSs now. They thought that the most important issues are an original long-term follow-up guideline suitable for the Japanese situation and collaborations with adult-based general physicians.
Many Japanese pediatric oncologists are uncomfortable with caring for survivors as they age and have suboptimal knowledge regarding late effects. The change in truth-telling situation and preference for collaboration with adult-based physicians was demonstrated also in Japan.

Long-term haematological improvement after non-intensive or no chemotherapy in juvenile myelomonocytic leukaemia and poor correlation with adult myelodysplasia spliceosome-related mutations
Kazuyuki Matsuda, Nao Yoshida, Shuhei Miura, Yozo Nakazawa, Kazuo Sakashita, Nobuyuki Hyakuna, Masahiro Saito, Fumiyo Kato, Atsushi Ogawa, Akihiro Watanabe, Manabu Sotomatsu, Chie Kobayashi, Toshiro Ito, Fumihiro Ishida, Atsushi Manabe, Seiji Kojima, Kenichi Koike
BRITISH JOURNAL OF HAEMATOLOGY, 157, 5, 647, 650, WILEY-BLACKWELL, 2012年06月, ［査読有り］
英語

The activity of the inosine triphosphate pyrophosphatase affects toxicity of 6-mercaptopurine during maintenance therapy for acute lymphoblastic leukemia in Japanese children
Yoichi Tanaka, Atsushi Manabe, Hisaya Nakadate, Kensuke Kondoh, Kozue Nakamura, Katsuyoshi Koh, Tomoyuki Utano, Akira Kikuchi, Takako Komiyama
LEUKEMIA RESEARCH, 36, 5, 560, 564, PERGAMON-ELSEVIER SCIENCE LTD, 2012年05月, ［査読有り］
英語, 研究論文（学術雑誌）, The association between inosine triphosphate pyrophosphatase (ITPA) activity and toxicity of 6-mercaptopurine (6-MP) was retrospectively evaluated in 65 Japanese children with acute lymphoblastic leukemia (ALL). Patients with an ITPA activity of less than 126 mu mol/h/gHb presented with hepatotoxicity more frequently than those with higher ITPA activity (p < 0.01). The average 6-MP dose during maintenance therapy administered to two patients with the ITPA deficiency was lower than that given to the other patients. Measuring ITPA activity is important for ensuring the safety of maintenance therapy for Asians with ALL because thiopurine S-methyl transferase mutations are rare in the Asian population. (C) 2011 Elsevier Ltd. All rights reserved.

乳癌患者の子どもへの支援に関する医師・看護師の意識調査　　　　　　　　　　　　　　　
小澤 美和, 大野 真司, 石田 也寸志, 武井 優子, 真部 淳
日本乳癌学会総会プログラム抄録集, 20回, 521, 521, (一社)日本乳癌学会, 2012年05月
日本語

[Myelodysplastic syndrome in childhood and juvenile myelomonocytic leukemia].
Hasegawa D, Manabe A
Nihon rinsho. Japanese journal of clinical medicine, 70 Suppl 2, 681, 686, 2012年04月, ［査読有り］

[Acute lymphoblastic leukemia (ALL)].
Manabe A
Nihon rinsho. Japanese journal of clinical medicine, 70 Suppl 2, 670, 675, 2012年04月, ［査読有り］

CBL mutation in chronic myelomonocytic leukemia secondary to familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML)
Norio Shiba, Daisuke Hasegawa, Myoung-ja Park, Chisato Murata, Aiko Sato-Otsubo, Chitose Ogawa, Atsushi Manabe, Hirokazu Arakawa, Seishi Ogawa, Yasuhide Hayashi
BLOOD, 119, 11, 2612, 2614, AMER SOC HEMATOLOGY, 2012年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML) is a rare autosomal dominant disease characterized by thrombocytopenia, abnormal platelet function, and a propensity to develop myelodysplastic syndrome (MDS) and AML. So far,> 20 affected families have been reported. Recently, a second RUNX1 alteration has been reported; however, no additional molecular abnormalities have been found so far. We identified an acquired CBL mutation and 11q-acquired uniparental disomy (11q-aUPD) in a patient with chronic myelomonocytic leukemia (CMML) secondary to FPD with RUNX1 mutation but not in the same patient during refractory cytopenia. This finding suggests that alterations of the CBL gene and RUNX1 gene may cooper-ate in the pathogenesis of CMML in patients with FPD/AML. The presence of CBL mutations and 11q-aUPD was an important "second hit" that could be an indicator of leukemic transformation of MDS or AML in patients with FPD/AML. (Blood. 2012;119(11):2612-2614)

Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15
Takeshi Inukai, Nobutaka Kiyokawa, Dario Campana, Elaine Coustan-Smith, Akira Kikuchi, Miyuki Kobayashi, Hiroyuki Takahashi, Katsuyoshi Koh, Atsushi Manabe, Masaaki Kumagai, Koichiro Ikuta, Yasuhide Hayashi, Masahiro Tsuchida, Kanji Sugita, Akira Ohara
BRITISH JOURNAL OF HAEMATOLOGY, 156, 3, 358, 365, WILEY-BLACKWELL, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Childrens Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5.5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P = 0.014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL.

TCCSGの小児B前駆細胞型急性リンパ性白血病におけるCRLF2とIKZF1、JAK遺伝子解析　　　　　　　　　　　　　　　
大木 健太郎, 大喜多 肇, 清河 信敬, 朴 明子, 康 勝好, 花田 良二, 真部 淳, 菊地 陽, 小原 明, 林 泰秀
日本小児科学会雑誌, 116, 2, 246, 246, (公社)日本小児科学会, 2012年02月
日本語

二相性の経過をとったHHV6脳症4症例の後方視的検討　　　　　　　　　　　　　　　
小野 林太郎, 居石 崇志, 稲井 郁子, 石田 也寸志, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 116, 2, 367, 367, (公社)日本小児科学会, 2012年02月
日本語

小児がん患児のきょうだいへの心理的サポート PTSD-RIを用いた縦断研究　　　　　　　　　　　　　　　
東 飛鳥, 小澤 美和, 小林 明雪子, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 小川 千登勢, 石田 也寸志, 真部 淳, 細谷 亮太
日本小児科学会雑誌, 116, 2, 310, 310, (公社)日本小児科学会, 2012年02月
日本語

The Utility of Performing the Initial Lumbar Puncture on Day 8 in Remission Induction Therapy for Childhood Acute Lymphoblastic Leukemia: TCCSG L99-15 Study
Daisuke Hasegawa, Atsushi Manabe, Akira Ohara, Akira Kikuchi, Katsuyoshi Koh, Nobutaka Kiyokawa, Takashi Fukushima, Yasushi Ishida, Tomohiro Saito, Ryoji Hanada, Masahiro Tsuchida
PEDIATRIC BLOOD & CANCER, 58, 1, 23, 30, WILEY PERIODICALS, INC, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Traumatic lumbar puncture with leukemic blasts (TLP+), which has been reported to occur 5-10%, in the previous studies, adversely affects the outcome of children with acute lymphoblasticleukemia(ALL). Based on the results from our previous study, we deferred the initial lumbar puncture until day 8 in remission induction therapy in order to reduce the frequency of cases with TLP+.. Procedure. The study was conducted as a prospective cohort study within the Tokyo Children's Cancer Study Group (TCCSG) L99-15 study. Between April 1999 and June 2003, 754 children with newly diagnosed ALL enrolled. The patients received the initial intrathecal chemotherapy after 7 days of prednisolonetreatment. The incidence of central nervous system (CNS)-positive (the presence of leukemicblasts in cerebrospinal fluid or cranial nerve palsy) including TLP+ cases and cumulative incidence of CNS relapse were examined. Results. The incidence of CNS-positive and TLP+ was 2.9% (n = 22) and 0.8% (n = 6), respectively. These incidencesweremuchlower than those in the representative study groups employing the initial IT on day 1. Of 22 patients with CNS-positive, only one patient relapsed in CNS, whereas 22 of the remaining CNS-negative 723 patients suffered from CNS relapse. Overall, event-free survival at 4 year was 78.2 +/- 1.6%. Four-year cumulative incidence of any CNS relapse was 3.3 +/- 0.7%, which improved from our previous study in spite of limiting the use of cranial irradiation. Conclusions. Our strategy reduced the frequency of CNS-positive patients who required reinforcement of CNS-directed therapy without compromising overall outcome. Pediatr Blood Cancer 2012; 58: 23-30. (C) 2011 Wiley Periodicals, Inc.

プライマリケア・マスターコース 小児科診療のすすめ 乳幼児突然死症候群(SIDS)
宮下 文織, 小野 林太郎, 長沖 優子, 石田 也寸志, 真部 淳, 細谷 亮太
日本医事新報, 4578, 46, 49, (株)日本医事新報社, 2012年01月
日本語

[Prognosis of 75 patients with juvenile myelomonocytic leukemia: prospective study by MDS committee in the Japanese Society of Pediatric Hematology].
Nao Yoshida, Shinsuke Hirabayashi, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Ayami Yoshimi, Atsuko Masunaga, Yoshitoshi Otsuka, Masafumi Ito, Seiji Kojima, Tatsutoshi Nakahata, Atsushi Manabe
[Rinsho ketsueki] The Japanese journal of clinical hematology, 52, 12, 1853, 8, 2011年12月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia (JMML) is a myelodysplastic/myeloproliferative disorder of young children. Because the disease is rare and the diagnosis is difficult, a prospective registration of patients suspected of having JMML with a pathological central review have been conducted by the MDS Committee of the Japanese Society of Pediatric Hematology. Between 1999 and 2006, 75 children with JMML were enrolled and diagnosed through this system. Median age at diagnosis was 20 months (1∼85 months). Cytogenetic abnormalities were detected in 21 patients, including 11 with monosomy 7. The 5-year overall survival (OS) was 60%. Regarding the treatment, 61 of the 75 patients received stem cell transplantation (SCT). Conditioning regimen varied widely, and the source of grafts was bone marrow for 43 patients, peripheral blood for 5, and cord blood for 13. The 5-year OS after SCT was 61%. Notably, patients who received cord blood transplantation had inferior survival than those who received grafts from other sources (38 vs. 68%; P=0.03). Given better recognition of the disease, a multi-center protocol study on SCT, JMML11, is now being planned by the Japanese Pediatric Leukemia/Lymphoma Study Group.

急性リンパ性白血病の維持療法における6-メルカプトプリン関連副作用発現へのTPMT、ITPA、MTHFR遺伝子型の影響　　　　　　　　　　　　　　　
田中 庸一, 真部 淳, 中舘 尚也, 近藤 健介, 中村 こずえ, 康 勝好, 菊地 陽, 歌野 智之, 小宮山 貴子
小児がん, 48, プログラム・総会号, 248, 248, (NPO)日本小児がん学会, 2011年11月
日本語

高2倍体(hyperdiploid)小児急性リンパ性白血病における増加染色体と予後との関連　　　　　　　　　　　　　　　
加藤 元博, 高橋 浩之, 清河 信敬, 福島 敬, 康 勝好, 真部 淳, 土田 昌宏, 小原 明, 東京小児がん研究グループ(TCCSG)
小児がん, 48, プログラム・総会号, 248, 248, (NPO)日本小児がん学会, 2011年11月
日本語

TCCSG-L0416臨床試験にみる完全寛解の定義が寛解割合に及ぼす影響　　　　　　　　　　　　　　　
牧本 敦, 小原 明, 花田 良二, 角南 勝介, 金子 隆, 熊谷 昌明, 真部 淳, 福島 敬, 磯山 恵一, 康 勝好, 井田 孔明, 前田 美穂, 黒澤 秀光, 後藤 裕明, 松井 敦, 菊地 陽, 土田 昌宏, 東京小児がん研究グループ(TCCSG)
小児がん, 48, プログラム・総会号, 249, 249, (NPO)日本小児がん学会, 2011年11月
日本語

小児急性リンパ性白血病高危険群に対するBFM95-HR強化療法 TCCSG ALL L99-1502研究　　　　　　　　　　　　　　　
康 勝好, 小原 明, 小川 千登世, 加藤 元博, 清河 信敬, 福島 敬, 嶋田 博之, 高橋 浩之, 梶原 道子, 菊地 陽, 真部 淳, 熊谷 昌明, 花田 良二, 林 泰秀, 土田 昌宏, 東京小児がん研究グループ(TCCSG)
小児がん, 48, プログラム・総会号, 250, 250, (NPO)日本小児がん学会, 2011年11月
日本語

小児ALL関連キメラ遺伝子発現量の末梢血中推移と既知リスク因子との関連について　　　　　　　　　　　　　　　
福島 敬, 南木 融, 清河 信敬, 小林 千恵, 福島 紘子, Shaza Mahmoud, 康 勝好, 菊地 陽, 真部 淳, 熊谷 昌明, 土田 昌宏, 林 泰秀, 小原 明, 東京小児がん研究グループ(TCCSG)
小児がん, 48, プログラム・総会号, 250, 250, (NPO)日本小児がん学会, 2011年11月
日本語

小児急性リンパ性白血病(ALL)症例における寛解導入不能例の検討 東京小児がん研究グループ(TCCSG)からの報告　　　　　　　　　　　　　　　
細谷 要介, 望月 慎史, 加藤 啓輔, 長谷川 大輔, 清河 信敬, 福島 敬, 康 勝好, 真部 淳, 土田 昌宏, 小原 明, 東京小児がん研究グループ(TCCSG)
小児がん, 48, プログラム・総会号, 313, 313, (NPO)日本小児がん学会, 2011年11月
日本語

小児急性リンパ性白血病(ALL)における低強度寛解導入療法に対する反応性 TCCSG L99-15研究より　　　　　　　　　　　　　　　
長谷川 大輔, 真部 淳, 小原 明, 菊地 陽, 康 勝好, 清河 信敬, 福島 敬, 石田 也寸志, 斎藤 友博, 花田 良二, 土田 昌宏, 東京小児がん研究グループ
小児がん, 48, プログラム・総会号, 314, 314, (NPO)日本小児がん学会, 2011年11月
日本語

対照的な経過をとったGATA-1変異陽性の非ダウン症AMKLの2症例　　　　　　　　　　　　　　　
小野 林太郎, 馬場 徳朗, 齋藤 怜, 米川 聡子, 吉原 宏樹, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 真部 淳, 細谷 亮太
小児がん, 48, プログラム・総会号, 321, 321, (NPO)日本小児がん学会, 2011年11月
日本語

小児がん患者が退院後に抱える心理社会的問題に関するパンフレット作成の試み　　　　　　　　　　　　　　　
武井 優子, 小澤 美和, 樋口 明子, 片山 麻子, 斎藤 秀子, 横川 めぐみ, 真部 淳, 尾形 明子, 鈴木 伸一
小児がん, 48, プログラム・総会号, 245, 245, (NPO)日本小児がん学会, 2011年11月
日本語

小児がん経験者の晩期合併症の予測は可能か 聖路加国際病院小児科の経験　　　　　　　　　　　　　　　
石田 也寸志, 渡辺 静, 小澤 美和, 米川 聡子, 小川 千登世, 長谷川 大輔, 細谷 要介, 吉原 宏樹, 真部 淳, 森本 克, 西村 昂三, 細谷 亮太
小児がん, 48, プログラム・総会号, 252, 252, (NPO)日本小児がん学会, 2011年11月
日本語

小児がん患者に対する妊孕性温存の現状についての検討　　　　　　　　　　　　　　　
米川 聡子, 小川 千登世, 小澤 美和, 齋藤 怜, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 塩田 恭子, 石田 也寸志, 真部 淳, 細谷 亮太
小児がん, 48, プログラム・総会号, 253, 253, (NPO)日本小児がん学会, 2011年11月
日本語

高機能広汎性発達障害を有する子どもの、小児がん入院治療への心理的サポート　　　　　　　　　　　　　　　
阿佐美 百合子, 小澤 美和, 小林 明雪子, 吉原 広樹, 長谷川 大輔, 小川 千登世, 真部 淳, 関富 晶子, 西野 理英, 細谷 亮太
小児がん, 48, プログラム・総会号, 353, 353, (NPO)日本小児がん学会, 2011年11月
日本語

WT1ワクチンを用いて寛解を保っている横紋筋肉腫の2例　　　　　　　　　　　　　　　
吉原 宏樹, 細谷 要介, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 澤田 明久, 井上 雅美, 橋井 佳子, 杉山 治夫, 真部 淳, 細谷 亮太
小児がん, 48, プログラム・総会号, 303, 303, (NPO)日本小児がん学会, 2011年11月
日本語

Clinical Characteristics and Treatment Outcome of Refractory Cytopenia of Childhood (RCC): A Prospective Registration Through the Japanese Society of Pediatric Hematology
Daisuke Hasegawa, Xiaojuan Chen, Shinsuke Hirabayashi, Yasushi Ishida, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Atsuko Masunaga, Ayami Yoshimi, Asahito Hama, Seiji Kojima, Masafumi Ito, Tatsutoshi Nakahata, Atsushi Manabe
BLOOD, 118, 21, 1199, 1199, AMER SOC HEMATOLOGY, 2011年11月, ［査読有り］
英語

Intellectual development after treatment in children with acute leukemia and brain tumor
Shizuka Watanabe, Yuriko Azami, Miwa Ozawa, Takahiro Kamiya, Daisuke Hasegawa, Chitose Ogawa, Yasushi Ishida, Ryota Hosoya, Junko Kizu, Atsushi Manabe
PEDIATRICS INTERNATIONAL, 53, 5, 694, 700, WILEY-BLACKWELL, 2011年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The influence of central nervous system (CNS)-directed chemotherapy on intelligence remains controversial. In this study, we investigated the influence of treatment on intellectual development in acute lymphoblastic leukemia (ALL) and brain tumor patients undergoing CNS-directed treatments.
Methods: Among patients treated in the Department of Pediatrics, St Luke's International Hospital between April 2000 and March 2009, the subjects were 38 patients with ALL or brain tumors who underwent regular Wechsler intelligence tests.
Results: The subjects consisted of 26 patients with ALL and 12 with brain tumors. Prophylactic cranial irradiation was not performed in patients with ALL, whereas it was done for all those with brain tumor. In patients with ALL, the IQ 1 year later was not changed from the start of treatment. In those with brain tumors, the verbal IQ 1 year later was significantly lower than that at the start of treatment. In patients with ALL, intelligence tests were performed 3 years after the start of treatment and there were no marked changes between the two time-points (n = 11). In those with a brain tumor, intellectual functions further decreased after the completion of treatment to as late as 5 years after the initiation of treatment (n = 7).
Conclusions: There is no intellectual impairment in any patient with ALL at post-treatment follow-up 3 years after the start of treatment, while intelligence is serially reduced in brain tumor patients. An innovative intervention may be needed for this group of patients.

MLL関連キメラが検出されないCD10陰性ALLのマーカーと発現遺伝子の特徴(Molecular characteristics and gene expression profiles of CD10-negative B-cell precursor ALL without MLL-rearrangements)　　　　　　　　　　　　　　　
清河 信敬, 飯島 一智, 加藤 元博, 福島 敬, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 藤本 純一郎, 林 泰秀, 小原 明
日本癌学会総会記事, 70回, 201, 201, (一社)日本癌学会, 2011年09月
英語

[Bone marrow findings of childhood aplastic anemia: analyses of 140 cases by central reviewers].
Hama A, Yoshimi A, Sakaguchi H, Doisaki S, Muramatsu H, Shimada A, Takahashi Y, Nozawa K, Ito M, Tsuchida M, Manabe A, Ohara A, Kojima S
[Rinsho ketsueki] The Japanese journal of clinical hematology, 52, 8, 653, 658, 2011年08月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, The revised WHO classification proposed the term "refractory cytopenia of childhood (RCC)" for children with myelodysplastic syndrome (MDS) with a low blast count. The differential diagnosis between RCC and aplastic anemia (AA) is challenging, especially when bone marrow is hypoplastic and there is no detectable chromosomal abnormality. To reveal the difference between AA and RCC with respect to the clinical and biological features, we retrospectively reviewed the bone marrow smears of 140 patients registered for childhood AA-97 study, which were classified into three groups as follows; the AA group was defined as having no morphologically dysplastic changes; the AA-RCC borderline group was defined as having <10% dysplastic changes in the erythroid lineage only; and the RCC group was defined as having dysplastic changes in more than two cell lineages or >10% in a single cell lineage. The patients were classified into the AA group (n=96, 69%), AA-RCC borderline group (n=20, 14%) and RCC group (n=24, 17%). Most of the patients in the AA group were classified as having very severe disease, whereas most of the patients in the RCC group were classified as non-severe disease. Only 2 patients in the AA group developed acute myeloid leukemia. The response rate to immunosuppressive therapy did not differ among the 3 groups. To demonstrate whether the two diseases are truly different entities, it is necessary to compare molecular backgrounds between the AA and RCC groups.

がんを持つ親の子どもへのサポートグループに関する研究　　　　　　　　　　　　　　　
小林 真理子, 大沢 かおり, 小澤 美和, 石田 也寸志, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 16回, 424, 424, (NPO)日本緩和医療学会, 2011年06月
日本語

がんになった患者の子どもへの病気説明に関する実態調査(その3) 説明を受けた子どもの反応(アンケートからの質的分析)　　　　　　　　　　　　　　　
井上 絵未, 大沢 かおり, 小林 真理子, 村瀬 有紀子, 茶園 美香, 井上 実穂, 衛藤 美穂, 三浦 絵莉子, 小澤 美和, 石田 也寸志, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 16回, 487, 487, (NPO)日本緩和医療学会, 2011年06月
日本語

がんになった患者の子どもへの病気説明に関する実態調査(その1) 患者へのアンケート・量的分析　　　　　　　　　　　　　　　
大沢 かおり, 井上 実穂, 小林 真理子, 石田 也寸志, 小澤 美和, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 16回, 488, 488, (NPO)日本緩和医療学会, 2011年06月
日本語

がんになった患者の子どもへの病気説明に関する実態調査(その2) がん患者が子供に病気を説明する背景　　　　　　　　　　　　　　　
村瀬 有紀子, 井上 実穂, 茶園 美香, 大沢 かおり, 井上 絵未, 衛藤 美穂, 小林 真理子, 三浦 絵莉子, 小澤 美和, 石田 也寸志, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 16回, 488, 488, (NPO)日本緩和医療学会, 2011年06月
日本語

肝芽腫を合併したUPD‐14の2例
野崎太希, 河野達夫, 清水光政, 草川功, 平田倫生, 槇殿文香理, 真部淳, 平林健, 細谷亮太, 齋田幸久
日本小児放射線学会雑誌, 27, 31, 2011年05月20日
日本語

生後早期に少量シタラビン (Ara-C) 療法を施行した一過性骨髄増殖症(TAM)の1例
中川 真智子, 草川 功, 平田 倫生, 齋藤 怜, 笠井 恵美, 長谷川 大輔, 真部 淳, 細谷 亮太
日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine, 47, 1, 161, 164, (一社)日本周産期・新生児医学会, 2011年05月01日
日本語, 妊娠35週0日、児心音異常のため母体搬送となり同日緊急帝王切開となった。児は血液検査にて著明な白血球数増加と血小板の増加、LDHの増加を認め一過性骨髄増殖症(TAM)が疑われたため日齢1に新生児搬送となった。白血球、血小板とも減少傾向で、補液、尿アルカリ化、アロプリノール投与のみで経過観察した。日齢1の血清総ビリルビン値は14.9mg/dlであったため光線療法を行い、SpO2の軽度低下に対し酸素投与を行った。染色体検査で21トリソミーと診断遺伝子検査でTAMと診断した。末梢血芽球の消失を認めず、日齢11より少量Ara-C療法を7日間行い日齢31に芽球消失を確認した。化学療法中全身状態は安定し、有害事象としては骨髄抑制を認め、濃厚赤血球の輸血を必要とした。日齢23には表皮ブドウ球菌菌血症に罹患したが抗菌薬投与にて改善した。日齢62に退院し、月齢10ヵ月現在も経過良好である。

Validation of the Japanese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module
Naoko Tsuji, Naoko Kakee, Yasushi Ishida, Keiko Asami, Ken Tabuchi, Hisaya Nakadate, Tsuyako Iwai, Miho Maeda, Jun Okamura, Takuro Kazama, Yoko Terao, Wataru Ohyama, Yuki Yuza, Takashi Kaneko, Atsushi Manabe, Kyoko Kobayashi, Kiyoko Kamibeppu, Eisuke Matsushima
HEALTH AND QUALITY OF LIFE OUTCOMES, 9, 22, BIOMED CENTRAL LTD, 2011年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The PedsQL 3.0 Cancer Module is a widely used instrument to measure pediatric cancer specific health-related quality of life (HRQOL) for children aged 2 to 18 years. We developed the Japanese version of the PedsQL Cancer Module and investigated its reliability and validity among Japanese children and their parents.
Methods: Participants were 212 children with cancer and 253 of their parents. Reliability was determined by internal consistency using Cronbach's coefficient alpha and test-retest reliability using intra-class correlation coefficient (ICC). Validity was assessed through factor validity, convergent and discriminant validity, concurrent validity, and clinical validity. Factor validity was examined by exploratory factor analysis. Convergent and discriminant validity were examined by multitrait scaling analysis. Concurrent validity was assessed using Spearman's correlation coefficients between the Cancer Module and Generic Core Scales, and the comparison of the scores of child self-reports with those of other self-rating depression scales for children. Clinical validity was assessed by comparing the on-and off-treatment scores using Kruskal-Wallis and Mann-Whitney U tests.
Results: Cronbach's coefficient alpha was over 0.70 for the total scale and over 0.60 for each subscale by age except for the 'pain and hurt' subscale for children aged 5 to 7 years. For test-retest reliability, the ICC exceeded 0.70 for the total scale for each age. Exploratory factor analysis demonstrated sufficient factorial validity. Multitrait scaling analysis showed high success rates. Strong correlations were found between the reports by children and their parents, and the scores of the Cancer Module and the Generic Core Scales except for 'treatment anxiety' subscales for child reports. The Depression Self-Rating Scale for Children (DSRS-C) scores were significantly correlated with emotional domains and the total score of the cancer module. Children who had been off treatment over 12 months demonstrated significantly higher scores than those on treatment.
Conclusions: The results demonstrate the reliability and validity of the Japanese version of the PedsQL Cancer Module among Japanese children.

10カラーフローサイトメトリー解析による小児白血病のマーカー診断　　　　　　　　　　　　　　　
清河 信敬, 山田 浩之, 康 勝好, 福島 敬, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明, 林 泰秀, 土田 昌宏
日本小児科学会雑誌, 115, 2, 328, 328, (公社)日本小児科学会, 2011年02月
日本語

Early T-cell precursor ALL同定のための汎用抗原を用いたスコアリング・システム　　　　　　　　　　　　　　　
犬飼 岳史, 清河 信敬, 高橋 浩之, 康 勝好, 真部 淳, 熊谷 昌明, 小原 明, Dario Campana, 杉田 完爾
小児がん, 47, プログラム・総会号, 282, 282, (NPO)日本小児がん学会, 2010年12月
日本語

小児急性リンパ性白血病中間危険群に対する早期強化療法としての大量cytarabine療法の意義 TCCSG L99-15研究　　　　　　　　　　　　　　　
康 勝好, 小原 明, 小川 千登世, 加藤 元博, 清河 信敬, 福島 敬, 嶋田 博之, 高橋 浩之, 梶原 道子, 菊地 陽, 真部 淳, 熊谷 昌明, 生田 孝一郎, 花田 良二, 林 泰秀, 土田 昌宏
小児がん, 47, プログラム・総会号, 285, 285, (NPO)日本小児がん学会, 2010年12月
日本語

東京小児がん研究グループ急性リンパ性白血病中央診断におけるEarly T-cell precursor ALLのマーカーの特徴　　　　　　　　　　　　　　　
清河 信敬, 犬飼 岳史, 高橋 浩之, 康 勝好, 杉田 完爾, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明, 林 泰秀, 土田 昌宏
小児がん, 47, プログラム・総会号, 396, 396, (NPO)日本小児がん学会, 2010年12月
日本語

東京小児がん研究グループ(TCCSG)ALL L07-1602の寛解導入療法におけるL-アスパラギナーゼの有害事象　　　　　　　　　　　　　　　
小川 千登世, 太田 節雄, 熊谷 昌明, 牧本 敦, 清河 信敬, 福島 敬, 康 勝好, 真部 淳, 花田 良二, 小原 明, 土田 昌宏
小児がん, 47, プログラム・総会号, 397, 397, (NPO)日本小児がん学会, 2010年12月
日本語

MLL関連キメラ遺伝子陽性小児急性白血病におけるMCSP抗原発現　　　　　　　　　　　　　　　
山田 浩之, 清河 信敬, 橋本 亙, 恩田 恵子, 飯島 一智, 福島 敬, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明
小児がん, 47, プログラム・総会号, 427, 427, (NPO)日本小児がん学会, 2010年12月
日本語

急性骨髄性白血病に対して化学療法施行中にα-Streptoccusによる髄膜炎、感染性心内膜炎を呈した1例　　　　　　　　　　　　　　　
小野 林太郎, 居石 崇志, 森山 貴也, 米川 聡子, 山本 剛士, 神谷 尚宏, 小川 千登世, 真部 淳, 野崎 太希, 篠田 正樹, 細谷 亮太
小児がん, 47, プログラム・総会号, 419, 419, (NPO)日本小児がん学会, 2010年12月
日本語

小児病棟の入院生活に対する悪性腫瘍児および家族の意識調査 付き添い家族の生活について考える　　　　　　　　　　　　　　　
吉川 久美子, 関冨 晶子, 永瀬 恭子, 天野 こころ, 平田 美佳, 石井 里奈, 大野 尚子, 神谷 尚宏, 長谷川 大輔, 真部 淳, 石田 也寸志, 細谷 亮太
小児がん, 47, プログラム・総会号, 273, 273, (NPO)日本小児がん学会, 2010年12月
日本語

小児病棟での生活に対する悪性腫瘍患児およびに家族の意識調査 携帯電話・ポータブルゲームを考える　　　　　　　　　　　　　　　
芹澤 裕子, 天野 こころ, 前田 邦枝, 永瀬 恭子, 関冨 晶子, 平田 美佳, 吉川 久美子, 大野 尚子, 石井 里奈, 長谷川 大輔, 神谷 尚宏, 石田 也寸志, 真部 淳, 細谷 亮太
小児がん, 47, プログラム・総会号, 295, 295, (NPO)日本小児がん学会, 2010年12月
日本語

小児がん患者における知的発達のフォローアップ(第2報)　　　　　　　　　　　　　　　
渡辺 静, 阿佐美 百合子, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 小澤 美和, 石田 也寸志, 木津 純子, 後藤 一美, 真部 淳, 細谷 亮太
小児がん, 47, プログラム・総会号, 253, 253, (NPO)日本小児がん学会, 2010年12月
日本語

骨髄移植のドナー候補となったきょうだいの心理的現状に関する検討　　　　　　　　　　　　　　　
小林 明雪子, 小澤 美和, 阿佐美 百合子, 東 飛鳥, 神谷 尚宏, 小川 千登世, 石田 也寸志, 真部 淳, 細谷 亮太
小児がん, 47, プログラム・総会号, 385, 385, (NPO)日本小児がん学会, 2010年12月
日本語

急性リンパ性白血病患児の同胞への心理的援助 弟を亡くした9歳女子の事例から　　　　　　　　　　　　　　　
阿佐美 百合子, 小澤 美和, 小林 明雪子, 長谷川 大輔, 小川 千登世, 真部 淳, 大野 尚子, 吉川 久美子, 細谷 亮太
小児がん, 47, プログラム・総会号, 386, 386, (NPO)日本小児がん学会, 2010年12月
日本語

小児がん患者における病気のとらえ方と退院後の困難の関連性の検討
武井 優子, 尾形 明子, 小澤 美和, 盛武 浩, 真部 淳, 平井 啓, 鈴木 伸一
日本行動療法学会大会発表論文集, 36回, 164, 165, (一社)日本認知・行動療法学会, 2010年12月
日本語

Clinical Outcome of Children With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005
Maurizio Arico, Martin Schrappe, Stephen P. Hunger, William L. Carroll, Valentino Conter, Stefania Galimberti, Atsushi Manabe, Vaskar Saha, Andre Baruchel, Kim Vettenranta, Keizo Horibe, Yves Benoit, Rob Pieters, Gabriele Escherich, Lewis B. Silverman, Ching-Hon Pui, Maria Grazia Valsecchi
JOURNAL OF CLINICAL ONCOLOGY, 28, 31, 4755, 4761, AMER SOC CLINICAL ONCOLOGY, 2010年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose
In a previous analysis of 326 children with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade.
Patients and Methods
We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years.
Results
Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% +/- 2.0% v 25.0% +/- 3.0, respectively, P = .007; and 44.9% +/- 2.2% v 36.0% +/- 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome.
Conclusion
Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL. J Clin Oncol 28: 4755-4761. (C) 2010 by American Society of Clinical Oncology

[Recent progress in acute lymphoblastic leukemia in childhood].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 51, 10, 1558, 1563, 一般社団法人 日本血液学会, 2010年10月, ［査読有り］
日本語

Bullous exudative retinal detachment due to infiltration of leukemic cells in a child with acute lymphoblastic leukemia
Kenichi Yoshida, Daisuke Hasegawa, Ayako Takusagawa, Itaru Kato, Chitose Ogawa, Nariaki Echizen, Kishiko Ohkoshi, Tatsuo Yamaguchi, Ryota Hosoya, Atsushi Manabe
INTERNATIONAL JOURNAL OF HEMATOLOGY, 92, 3, 535, 537, SPRINGER TOKYO, 2010年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Acute lymphoblastic leukemia (ALL) is known to cause several ocular involvements, but exudative retinal detachment is a rare complication. We describe a case report of a 4-year-old boy with T cell ALL who developed bilateral exudative retinal detachment caused by leukemic infiltration in the retinas after achieving hematological remission. Intravenous steroid pulse therapy and local irradiation reversed the condition, but it recurred concurrently with disease progression after a second relapse in the bone marrow. It is suggested that ophthalmic examination is crucial for ALL patients, especially for those whose white blood cell count is very high at onset.

Congenital dyserythropoietic anemia
Takahiro Kamiya, Atsushi Manabe
INTERNATIONAL JOURNAL OF HEMATOLOGY, 92, 3, 432, 438, SPRINGER TOKYO, 2010年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of rare hereditary disorders of erythropoiesis characterized by morphologic abnormal erythroblasts in the bone marrow. Three types of the disease are known as type I, II and III, and the variant type of CDA and several minor subgroups of CDA have been also reported since the first classification. Recently, responsible genes for type I (CDAN1) and type II (SEC23B) have been identified and the molecular pathogenesis of the disease is currently being explored. Although CDAs rarely transform to myelodysplastic syndrome or leukemia, the disease is important to understand the mechanism of hemopoiesis in humans.

小児白血病のマーカー中央診断に対する10カラーフローサイトメトリー解析の有用性　　　　　　　　　　　　　　　
清河 信敬, 恩田 恵子, 橋本 亙, 長谷川 大輔, 飯島 一智, 福島 敬, 齋藤 正博, 藤本 純一郎, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明, 林 泰秀, 土田 昌宏
臨床血液, 51, 9, 1153, 1153, (一社)日本血液学会-東京事務局, 2010年09月
日本語

急性リンパ節白血病(ALL)治療後に海馬硬化を伴う難治性側頭葉てんかんを発症した女児例　　　　　　　　　　　　　　　
笠井 恵美, 荻原 正明, 小澤 美和, 真部 淳, 草川 功, 野崎 太希, 森本 克, 細谷 亮太
てんかん研究, 28, 2, 300, 300, (一社)日本てんかん学会, 2010年09月
日本語

[Molecular biology of juvenile myelomonocytic leukemia (JMML)].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 51, 7, 526, 531, 2010年07月, ［査読有り］

Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations
Yuka Sugimoto, Hideki Muramatsu, Hideki Makishima, Courtney Prince, Anna M. Jankowska, Nao Yoshida, Yinyan Xu, Nobuhiro Nishio, Asahito Hama, Hiroshi Yagasaki, Yoshiyuki Takahashi, Koji Kato, Atsushi Manabe, Seiji Kojima, Jaroslaw P. Maciejewski
BRITISH JOURNAL OF HAEMATOLOGY, 150, 1, 83, 87, WILEY-BLACKWELL, 2010年07月, ［査読有り］
英語, 研究論文（学術雑誌）, P>Mutations in NF1, PTPN11, NRAS, KRAS and CBL have been reported to play a pathogenetic role in juvenile myelomonocytic leukaemia (JMML), a rare myelodyplastic/myeloproliferative neoplasm occurring in children. Recently, mutations in ASXL1 were identified in chronic myelomonocytic leukaemia and other myeloid malignancies. We sequenced exon 12 of ASLX1 in 49 JMML patients, and found 2 novel heterozygous (nonsense and frameshift) mutations, one occurring as a sole lesion, the other was in conjunction with a PTPN11 mutation. ASXL1 cooperates with KDM1A in transcriptional repression and thereby ASXL1 mutations may synergize with or mimic other JMML-related mutations.

5カラーおよび10カラーによる小児白血病のマーカー中央診断　　　　　　　　　　　　　　　
清河 信敬, 恩田 恵子, 橋本 亙, 山田 浩之, 高野 邦彦, 飯島 一智, 福島 敬, 藤本 純一郎, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明, 林 泰秀, 土田 昌宏
Cytometry Research, 20, Suppl., 65, 65, (一社)日本サイトメトリー学会, 2010年06月
日本語

小児白血病におけるCD244の発現　　　　　　　　　　　　　　　
山田 浩之, 清河 信敬, 恩田 恵子, 橋本 亙, 飯島 一智, 福島 敬, 斎藤 正博, 藤本 純一郎, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明, 林 泰秀, 土田 昌宏
Cytometry Research, 20, Suppl., 65, 65, (一社)日本サイトメトリー学会, 2010年06月
日本語

がんを持つ親の子どもへの支援に関する活動報告　　　　　　　　　　　　　　　
大沢 かおり, 藤井 あけみ, 村瀬 有紀子, 伊藤 ゆかり, 井上 絵未, 中島 美鈴, 村田 和恵, 小林 真理子, 小澤 美和, 石田 也寸志, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 15回, 212, 212, (NPO)日本緩和医療学会, 2010年06月
日本語

がんを持つ親の子どもへの介入に関する実態調査 医療関係者へのアンケート分析(その1) 量的分析　　　　　　　　　　　　　　　
小林 真理子, 石田 也寸志, 茶園 美香, 小澤 美和, 井上 実穂, 大沢 かおり, 村田 和恵, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 15回, 214, 214, (NPO)日本緩和医療学会, 2010年06月
日本語

がんを持つ親の子どもへの介入に関する実態調査 医療関係者へのアンケート分析(その2) 量的分析　　　　　　　　　　　　　　　
衛藤 美穂, 小澤 美和, 井上 実穂, 小林 真理子, 西野 なお子, 茶園 美香, 大沢 かおり, 石田 也寸志, 真部 淳
日本緩和医療学会学術大会プログラム・抄録集, 15回, 214, 214, (NPO)日本緩和医療学会, 2010年06月
日本語

乳がん患者とその子どもへのサポートを考える CLS介入事例　　　　　　　　　　　　　　　
衛藤 美穂, 伊藤 ゆかり, 小澤 美和, 中島 美鈴, 小林 真理子, 真部 淳
日本乳癌学会総会プログラム抄録集, 18回, 655, 655, (一社)日本乳癌学会, 2010年05月
日本語

乳がん患者とその子どもへのサポートを考える 親子で乳がんを考える絵本の作成　　　　　　　　　　　　　　　
中島 美鈴, 小澤 美和, 伊藤 ゆかり, 衛藤 美穂, 小林 真理子, 真部 淳
日本乳癌学会総会プログラム抄録集, 18回, 656, 656, (一社)日本乳癌学会, 2010年05月
日本語

急速に呼吸障害が進行した小児のパンデミック(H1N1)2009による急性肺炎の2例　　　　　　　　　　　　　　　
神谷 尚宏, 森山 貴也, 中島 健太郎, 佐藤 真洋, 山本 剛士, 斎藤 怜, 笠井 恵美, 吉田 健一, 中川 真智子, 長谷川 大輔, 小松 なぎさ, 稲井 郁子, 平田 倫生, 小川 千登世, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太, 片山 正夫
日本小児科学会雑誌, 114, 4, 746, 746, (公社)日本小児科学会, 2010年04月
日本語

Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia
Hideki Muramatsu, Hideki Makishima, Anna M. Jankowska, Heather Cazzolli, Christine O'Keefe, Nao Yoshida, Yinyan Xu, Nobuhiro Nishio, Asahito Hama, Hiroshi Yagasaki, Yoshiyuki Takahashi, Koji Kato, Atsushi Manabe, Seiji Kojima, Jaroslaw P. Maciejewski
BLOOD, 115, 10, 1969, 1975, AMER SOC HEMATOLOGY, 2010年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. When we investigated the presence of recurrent molecular lesions in a cohort of 49 children with JMML, neurofibromatosis phenotype (and thereby NF1 mutation) was present in 2 patients (4%), whereas previously described PTPN11, NRAS, and KRAS mutations were found in 53%, 4%, and 2% of cases, respectively. Consequently, a significant proportion of JMML patients without identifiable pathogenesis prompted our search for other molecular defects. When we applied single nucleotide polymorphism arrays to JMML patients, somatic uniparental disomy 11q was detected in 4 of 49 patients; all of these cases harbored RING finger domain c-Cbl mutations. In total, c-Cbl mutations were detected in 5 (10%) of 49 patients. No mutations were identified in Cbl-b and TET2. c-Cbl and RAS pathway mutations were mutually exclusive. Comparison of clinical phenotypes showed earlier presentation and lower hemoglobin F levels in patients with c-Cbl mutations. Our results indicate that mutations in c-Cbl may represent key molecular lesions in JMML patients without RAS/PTPN11 lesions, suggesting analogous pathogenesis to those observed in chronic myelomonocytic leukemia (CMML) patients. (Blood. 2010; 115: 1969-1975)

当院における小児のインフルエンザA(H1N1)pdm感染症の受診動向および重症例のまとめ　　　　　　　　　　　　　　　
神谷 尚宏, 中島 健太郎, 笠井 恵美, 中川 真智子, 長谷川 大輔, 稲井 郁子, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 114, 2, 215, 215, (公社)日本小児科学会, 2010年02月
日本語

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999
M. Tsuchida, A. Ohara, A. Manabe, M. Kumagai, H. Shimada, A. Kikuchi, T. Mori, M. Saito, M. Akiyama, T. Fukushima, K. Koike, M. Shiobara, C. Ogawa, T. Kanazawa, Y. Noguchi, S. Oota, Y. Okimoto, H. Yabe, M. Kajiwara, D. Tomizawa, K. Ko, K. Sugita, T. Kaneko, M. Maeda, T. Inukai, H. Goto, H. Takahashi, K. Isoyama, Y. Hayashi, R. Hosoya, R. Hanada
LEUKEMIA, 24, 2, 383, 396, NATURE PUBLISHING GROUP, 2010年02月, ［査読有り］
英語, 研究論文（学術雑誌）, We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS) +/- s.e. was 67.2 +/- 2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0 +/- 1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because 460% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate-or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8mg/m(2) had no advantage over prednisolone 60mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies. Leukemia (2010) 24, 383-396; doi: 10.1038/leu.2009.260; published online 24 December 2009

小児がん患者が退院後に抱える心理社会的問題に関する研究の現状と課題　　　　　　　　　　　　　　　
武井優子, 尾形明子, 小澤美和, 真部淳, 鈴木伸一
小児がん, 47, 1, 84, 90, 2010年, ［査読有り］
日本語, 研究論文（学術雑誌）

Cytomegalovirus Infection Mimicking Juvenile Myelomonocytic Leukemia Showing Hypersensitivity to Granulocyte-Macrophage Colony Stimulating Factor
Hiroshi Moritake, Toshio Ikeda, Atsushi Manabe, Sachiyo Kamimura, Hiroyuki Nunoi
PEDIATRIC BLOOD & CANCER, 53, 7, 1324, 1326, WILEY-LISS, 2009年12月, ［査読有り］
英語, 研究論文（学術雑誌）, We describe an infant with cytomegalovirus (CMV) infection presenting as transient myeloproliferation resembling juvenile myelomonocytic leukemia (JMML). The patient fulfilled the international diagnostic criteria of JMML, including hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). Viral studies using serologic assays and polymerase chain reaction (PCR) were positive for CMV. Clinical symptoms disappeared and laboratory values returned to normal without specific treatment within I year. Follow-up showing a decrease in viral titers Suggested CMV infection as an etiologic factor for the development of myeloproliferative features. We conclude that the CMV infection transiently induced abnormal myelopoiesis in this infant. Pediatr Blood Cancer 2009;53:1324-1326. (C) 2009 Wiley-Liss, Inc.

Treatment of Children With Refractory Anemia: The Japanese Childhood MDS Study Group Trial (MDS99)
Daisuke Hasegawa, Atsushi Manabe, Hiroshi Yagasaki, Yoshitoshi Ohtsuka, Masami Inoue, Akira Kikuchi, Akira Ohara, Masahiro Tsuchida, Seiji Kojima, Tatsutoshi Nakahata
PEDIATRIC BLOOD & CANCER, 53, 6, 1011, 1015, WILEY-LISS, 2009年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background Although hematopoietic stern cell transplantation (HSCT) is offered as a Curative therapy for pediatric myelodysplastic syndrome (MDS), it may Cause severe complications and mortality. Several reports have shown the efficacy of immunosuppressive therapy (IST) in adult patients with refractory anemia (RA), but its safety and efficacy remains to be fully elucidated in childhood RA. Procedure. Eleven children diagnosed with RA and enrolled on a prospective multicenter trial conducted by the Japanese Childhood MDS Study Group were eligible for analysis. if patients showed transfusion dependent or suffered from infection due to neutropenia, they received IST consisting of antithymocyte globulin (ATG), cyclosporine (CyA), and methylprednisolone (mPSL.). Results. Eight children received IST, 2 received Only Supportive therapy, and one underwent HSCT without IST. Five (63%) of eight children who received IST showed hematological response. Of note, one patient showed the disappearance of monosomy 7 after IST. Responders were significantly younger than non-responders (29 months vs. 140 months; P=0.03). No severe adverse events related to IST were reported in this study. Of 6 children with chromosomal abnormalities who received IST, four showed hematological response. The probability of failure-free and overall survival at 5 years was 63 +/- 17% and 90 +/- 9% respectively. Conclusion. IST is likely to be a safe and effective modality for childhood RA. Pediatr Blood Cancer 2009;53:1011-1015. (C) 2009 Wiley-Liss, Inc.

泌尿生殖器領域の横紋筋肉腫に対する外科の役割について　　　　　　　　　　　　　　　
中村 晃子, 平林 健, 松藤 凡, 小川 千登世, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 218, 218, (NPO)日本小児がん学会, 2009年11月
日本語

脾臓摘出術後に同種臍帯血移植を行なった再発RBM15-MKL1陽性急性巨核芽球性白血病の一例　　　　　　　　　　　　　　　
長谷川 大輔, 神谷 尚宏, 吉田 健一, 中島 健太郎, 有馬 慶太郎, 平林 真介, 中村 晃子, 平林 健, 松藤 凡, 小川 高史, 藤原 美恵子, 鈴木 高祐, 小川 千登世, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 407, 407, (NPO)日本小児がん学会, 2009年11月
日本語

東京小児がん研究グループ急性リンパ性白血病第16次治療研究におけるマーカー中央診断　　　　　　　　　　　　　　　
清河 信敬, 恩田 恵子, 平林 真介, 飯島 一智, 福島 敬, 齋藤 正博, 藤本 純一郎, 真部 淳, 康 勝好, 熊谷 昌明, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏
小児がん, 46, プログラム・総会号, 226, 226, (NPO)日本小児がん学会, 2009年11月
日本語

日本人小児ALLにおけるBFM95 protocol Mに基づいた5g/m2 MTX投与の安全性に関する検討　　　　　　　　　　　　　　　
大隅 朋生, 小川 千登世, 康 勝好, 嶋 晴子, 三春 晶嗣, 大久保 淳, 真部 淳, 嶋田 博之
小児がん, 46, プログラム・総会号, 229, 229, (NPO)日本小児がん学会, 2009年11月
日本語

治療中再発に対してimatinib併用Hyper-CVAD療法による第2寛解導入後にHLA一致同胞間移植を行ったPh+ALLの2例　　　　　　　　　　　　　　　
有馬 慶太郎, 長谷川 大輔, 中島 健太郎, 吉田 健一, 平林 真介, 神谷 尚宏, 小川 千登世, 小澤 美和, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 231, 231, (NPO)日本小児がん学会, 2009年11月
日本語

Parvovirus B19感染によりaplastic crisisを来たしたcongenital dyserythropoietic anemia type 2の1例　　　　　　　　　　　　　　　
笠井 恵美, 神谷 尚宏, 長谷川 大輔, 中島 健太郎, 吉田 健一, 小川 千登世, 小澤 美和, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 302, 302, (NPO)日本小児がん学会, 2009年11月
日本語

小児がん患児のきょうだいにおける心理・社会的問題の検討 きょうだいの心理的現状　　　　　　　　　　　　　　　
小林 明雪子, 小澤 美和, 阿佐美 百合子, 長谷川 大輔, 小川 千登世, 石田 也寸志, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 346, 346, (NPO)日本小児がん学会, 2009年11月
日本語

小児がん患児のきょうだいにおける心理・社会的問題の検討 きょうだい自身の意見　　　　　　　　　　　　　　　
小林 明雪子, 小澤 美和, 阿佐美 百合子, 長谷川 大輔, 小川 千登世, 石田 也寸志, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 346, 346, (NPO)日本小児がん学会, 2009年11月
日本語

家族性網膜芽細胞腫の治療後に2次性の横紋筋肉腫を発症した一例　　　　　　　　　　　　　　　
中島 健太郎, 山本 剛士, 笠井 恵美, 吉田 健一, 平林 真介, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 石田 也寸志, 小澤 美和, 真部 淳, 細谷 亮太
小児がん, 46, プログラム・総会号, 369, 369, (NPO)日本小児がん学会, 2009年11月
日本語

MYCN増幅の獲得とともに進行性の経過をたどった神経芽腫StageIVの乳児例　　　　　　　　　　　　　　　
吉田 健一, 真部 淳, 山本 剛士, 中島 健太郎, 平林 真介, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 小澤 美和, 中村 晃子, 平林 健, 藤原 美恵子, 鈴木 高祐, 中川 温子, 上條 岳彦, 中川原 章, 細谷 亮太
小児がん, 46, プログラム・総会号, 370, 370, (NPO)日本小児がん学会, 2009年11月
日本語

小児がんに罹患した子どもの同胞への心理面でのケア 弟を亡くした3歳児の事例から　　　　　　　　　　　　　　　
武田 洋子, 小澤 美和, 相良ローゼンマイヤ みはる, 真部 淳, 小川 千登世, 長谷川 大輔, 神谷 尚宏, 平林 真介, 吉田 健一, 中島 健太郎, 山本 剛士, 細谷 亮太
小児がん, 46, プログラム・総会号, 416, 416, (NPO)日本小児がん学会, 2009年11月
日本語

小児がん患者が退院後に抱える病気や体調面に関する困難の検討　　　　　　　　　　　　　　　
武井 優子, 尾形 明子, 鈴木 伸一, 小澤 美和, 盛武 浩, 平井 啓, 真部 淳
小児がん, 46, プログラム・総会号, 419, 419, (NPO)日本小児がん学会, 2009年11月
日本語

The ex vivo production of ammonia predicts L-asparaginase biological activity in children with acute lymphoblastic leukemia
Shizuka Watanabe, Kumiko Miyake, Chitose Ogawa, Haruna Matsumoto, Kenichi Yoshida, Shinsuke Hirabayashi, Daisuke Hasegawa, Tadao Inoue, Junko Kizu, Reiko Machida, Akira Ohara, Ryota Hosoya, Atsushi Manabe
INTERNATIONAL JOURNAL OF HEMATOLOGY, 90, 3, 347, 352, SPRINGER TOKYO, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Patients with acute lymphoblastic leukemia (ALL), who develop antiasparaginase antibodies without clinical allergic reactions ("silent inactivation'') during L-asparaginase (L-Asp) treatment, have poor outcomes. Ammonia is produced by hydrolysis of asparagine by L-Asp. We postulated that plasma ammonia level might reflect the biological activity of L-Asp. Five children with ALL treated according to the Tokyo Children's Cancer Study Group (TCCSG) protocol were enrolled. Plasma ammonia levels were analyzed immediately and 1 h after incubation at room temperature and "ex vivo ammonia production'' was defined as increase in ammonia concentration. Ex vivo ammonia production well correlated with L-Asp activity (r = 0.882, P < 0.01, n = 23). It always exceeded 170 mu g/dL (170-345 mu g/dL) in induction therapy. We found 3 patients whose ammonia production was negligible during later phases of therapy. Antiasparaginase antibody was detected and L-Asp activity decreased in these patients. Ex vivo ammonia production is a surrogate marker of L-Asp biological activity.

Detection of submicroscopic disease in the bone marrow and unaffected testis of a child with T-cell acute lymphoblastic leukemia who experienced "isolated" testicular relapse
Keitaro Arima, Daisuke Hasegawa, Chitose Ogawa, Itaru Kato, Toshihiro Imamura, Ayako Takusagawa, Hiroka Takahashi, Yoshiro Kitagawa, Toshinari Hori, Masahito Tsurusawa, Atsushi Manabe, Ryota Hosoya
INTERNATIONAL JOURNAL OF HEMATOLOGY, 90, 3, 370, 373, SPRINGER TOKYO, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Testicular relapse has an impact on the prognosis of boys with acute lymphoblastic leukemia (ALL). Because isolated testicular relapse often precedes hematological relapse, systemic therapy is required in addition to local therapy. However, a rationale for the use of a combination of systemic chemotherapy and local therapy is unclear. A 12-year-old boy with T-ALL suffered from isolated testicular relapse at 27 months after diagnosis. He was successfully treated with systemic chemotherapy with orchiectomy and prophylactic irradiation to the contralateral testis. We retrospectively estimated the minimal residual disease in the bone marrow (BM) and the testis by detection of clone-specific T-cell receptor rearrangement of leukemic cells. We detected leukemic cells in the affected testis at relapse, as well as in the BM at initial diagnosis. In addition, we confirmed submicroscopic disease in the unaffected testis and the BM at relapse. We conclude that molecular analysis could reveal the submicroscopic disease in the patient with apparently isolated testicular relapse. This finding may provide a rationale for intensified systemic treatment of patients with isolated testicular relapse.

乳癌患者の闘病生活がその子どもへ与える心理・行動学影響　　　　　　　　　　　　　　　
小澤 美和, 伊藤 ゆかり, 真部 淳, 山内 英子, 中村 清吾, 細谷 亮太
日本癌治療学会誌, 44, 2, 845, 845, (一社)日本癌治療学会, 2009年09月
日本語

発作性の左下肢感覚異常に引き続いて部分運動発作重積状態を呈した右頭頂葉てんかんの一例(A case of right parietal lobe epilepsy showing repetitive paroxysmal irritation of left lower extremity developing clonic seizure of left leg)　　　　　　　　　　　　　　　
笠井 恵美, 山本 剛士, 吉田 健一, 中島 健太郎, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太, 荻原 正明
てんかん研究, 27, 2, 266, 266, (一社)日本てんかん学会, 2009年09月
英語

Metachronous gliomas following cranial irradiation for mixed germ cell tumors
Akari Makidono, Nobuo Kobayashi, Yukihisa Saida, Atsushi Manabe, Jiro Kawamori, Koyu Suzuki
CHILDS NERVOUS SYSTEM, 25, 6, 713, 718, SPRINGER, 2009年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Cranial irradiation has been widely used as a therapeutic tool for treating various lesions, particularly neoplastic diseases. Even though radiation therapy is usually well-tolerated, it occasionally causes clinically significant long-term toxicity such as radiation necrosis and irradiation-related arteriopathy with stroke.
The development of neoplasms following therapeutic cranial irradiation is also rare, but may cause serious and potentially fatal complications. Various radiation-induced tumors, including meningioma, glioma, and sarcoma have been reported (Child Nerv Syst 24:793-805, 12). However, metachronous intracranial double tumors induced by radiation therapy are extremely rare. In here, we report a case of metachronous different gliomas including astrocytoma and glioblastoma following irradiation therapy after 41 and 46 months, respectively.

9 colorフローサイトメトリーによる小児白血病のマーカー解析　　　　　　　　　　　　　　　
清河 信敬, 恩田 恵子, 高野 邦彦, 藤本 純一郎, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏
Cytometry Research, 19, 抄録集, 56, 56, (一社)日本サイトメトリー学会, 2009年06月
日本語

Correlation of Clinical Features With the Mutational Status of GM-CSF Signaling Pathway-Related Genes in Juvenile Myelomonocytic Leukemia
Nao Yoshida, Hiroshi Yagasaki, Yinyan Xu, Kazuyuki Matsuda, Ayami Yoshimi, Yoshiyuki Takahashi, Asahito Hama, Nobuhiro Nishio, Hideki Muramatsu, Nobuhiro Watanabe, Kimikazu Matsumoto, Koji Kato, Junichi Ueyama, Hiroko Inada, Hiroaki Goto, Miharu Yabe, Kazuko Kudo, Junichi Mimaya, Akira Kikuchi, Atsushi Manabe, Kenichi Koike, Seiji Kojima
PEDIATRIC RESEARCH, 65, 3, 334, 340, INT PEDIATRIC RESEARCH FOUNDATION, INC, 2009年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Mutations in RAS, neurofibromatosis type 1 (NF1), and PTPN11, constituents of the granulocyte-macrophage colony-stimulating factor signaling pathway, have been recognized in patients with juvenile myelomonocytic leukemia (JMML). We assessed 71 children with JMML for NRAS, KRAS. and PTPN11 mutations and evaluated their clinical significance. Of the 71 patients, three had been clinically diagnosed with neurofibromatosis type 1, and PTPN11 and NRAS/KRAS mutations were found in 32 (45%) and 13 (18%) patients, respectively. No Simultaneous aberrations were found. Compared with patients with RAS Mutation or without any aberrations, patients with PTPN11 mutation were significantly older at diagnosis and had higher fetal Hb levels, both of which have been recognized as poor prognostic factors. As was expected, overall survival was lower for patients with the PTPN11 mutation than for those without (25 versus 64%; p = 0.0029). In an analysis of 48 patients who received hematopoietic stein cell transplantation, PTPN11 mutations were also associated with poor prognosis for survival. Mutation in PTPN11 was the only unfavorable factor for relapse after hematopoietic stem cell transplantation (p = 0.001). All patients who died after relapse had PTPN11 mutation. These results suggest that JMML with PTPN11 mutation might be a distinct subgroup with specific clinical characteristics and poor outcome.

当院乳児健診受診児における排便状況と関連因子の検討　　　　　　　　　　　　　　　
中川 真智子, 鶴田 志緒, 中村 晃子, 小澤 美和, 真部 淳, 草川 功, 松藤 凡, 細谷 亮太
日本小児科学会雑誌, 113, 2, 350, 350, (公社)日本小児科学会, 2009年02月
日本語

頸部絞扼事故を契機に診断した広範性発達障害の一例　　　　　　　　　　　　　　　
山本 剛士, 笠井 恵美, 吉田 健一, 中島 健太郎, 平林 真介, 有馬 慶太郎, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 113, 2, 359, 359, (公社)日本小児科学会, 2009年02月
日本語

親と死別する子どもへの介入の経験　　　　　　　　　　　　　　　
小澤 美和, 真部 淳, 石田 也寸志, 草川 功, 細谷 亮太
日本小児科学会雑誌, 113, 2, 457, 457, (公社)日本小児科学会, 2009年02月
日本語

聖路加国際病院のレジデント教育(第14報) 後期研修医の受け入れを開始してから　　　　　　　　　　　　　　　
比嘉 千明, 吉田 健一, 中島 健太郎, 有馬 慶太郎, 平林 信介, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 113, 2, 464, 464, (公社)日本小児科学会, 2009年02月
日本語

01. 脾臓摘出術を先行して同種臍帯血移植を行った再発急性巨核芽球性白血病の1例(一般演題,第22回日本小児脾臓研究会)
長谷川 大輔, 神谷 尚宏, 吉田 健一, 中島 健太郎, 有馬 健太郎, 平林 真介, 中村 晃子, 平林 健, 松藤 凡, 小川 高史, 藤原 美恵子, 鈴木 高祐, 小川 千登世, 真部 淳, 細谷 亮太
日本小児外科学会雑誌, 45, 4, 803, 803, 特定非営利活動法人 日本小児外科学会, 2009年
日本語

A conditioning regimen of busulfan, fludarabine, and melphalan for allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia
Miharu Yabe, Masahiro Sako, Hiromasa Yabe, Yuko Osugi, Hidemitsu Kurosawa, Taemi Nara, Mika Tokuyama, Souichi Adachi, Chie Kobayashi, Masakatsu Yanagimachi, Yoshitoshi Ohtsuka, Yozo Nakazawa, Chitose Ogawa, Atsushi Manabe, Seiji Kojima, Tatsutoshi Nakahata
PEDIATRIC TRANSPLANTATION, 12, 8, 862, 867, WILEY-BLACKWELL, 2008年12月, ［査読有り］
英語, 研究論文（学術雑誌）, A pilot study was undertaken using a myeloablative conditioning with fludarabine, busulfan, and melphalan to improve the outcome of HSCT in 10 children, aged six months to six yr, with JMML. All patients were conditioned with oral busulfan (560 mg/m(2)), fludarabine (120 mg/m(2)), and melphalan (180-210 mg/m(2)) prior to HSCT, and received stem cells from bone marrow in seven cases, and from cord blood in three cases. Engraftment was documented in eight patients, whereas graft failure occurred in two, one of whom had received HLA-mismatched cord blood and other had received bone marrow from HLA-mismatched mother. Three patients, including two in who graft failure had occurred, relapsed. Five patients developed acute GVHD and two developed chronic GVHD. Seven patients are alive and in remission 27-69 months after transplantation. Thus, our study showed that HSCT following conditioning with fludarabine, busulfan, and melphalan was well tolerated and appeared to be effective for JMML.

Clinicopathological characteristics of erythroblast-rich RAEB and AML M6a in children
Yuko Honda, Atsushi Manabe, Masahiro Tsuchida, Yuji Zaike, Atsuko Masunaga, Masami Inoue, Ryoji Kobayashi, Yoshitoshi Ohtsuka, Akira Kikuchi, Tatsutoshi Nakahata
INTERNATIONAL JOURNAL OF HEMATOLOGY, 88, 5, 524, 529, SPRINGER TOKYO, 2008年12月, ［査読有り］
英語, 研究論文（学術雑誌）, The distinction between RAEB, RAEB-T and AML M6a is difficult when erythroblasts in the bone marrow (BM) exceed 50%. We analyzed 19 children (2 RAEB, 13 RAEB-T and 4 AML M6a) enrolled in a prospective pathological central review in Japan and divided them into two groups according to the myeloblasts percentage among non-erythroid cells in BM: group A (n = 8), 5-19% myeloblasts; group B (n = 11), 20% or more myeloblasts. Their characteristics were very similar except for the number of myeloblasts. The median WBC was in the range of 1.0-5.0 x 10(9) L(-1), the median Hb was around 7.5 g/dL, the median MCV was greater than 90 fL and both group had Auer rods at 60-65%. Severe multi-lineage dysplasia was observed in most of the patients in two groups. Six with group A and seven with group B treated with AML type chemotherapy achieved complete remission. Five with group A and seven with group B undergoing SCT are alive at a median of 3 years after diagnosis. Erythroblast-rich RAEB and AML M6a in children have similar characteristics and may belong to a single disease entity.

Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts
Ghulam J. Mufti, John M. Bennett, Jean Goasguen, Barbara J. Bain, Irith Baumann, Richard Brunning, Mario Cazzola, Pierre Fenaux, Ulrich Germing, Eva Hellstrom-Lindberg, Itsuro Jinnai, Atsushi Manabe, Akira Matsuda, Charlotte M. Niemeyer, Guillermo Sanz, Masao Tomonaga, Teresa Vallespi, Ayami Yoshimi
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 93, 11, 1712, 1717, FERRATA STORTI FOUNDATION, 2008年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The classification of myelodysplastic syndromes is based on the morphological criteria proposed by the French-American-British (FAB) and World Health Organization (WHO) groups. Accurate enumeration of blast cells, although essential for diagnosis of myelodysplastic syndrome and for assignment to prognostic groups, is often difficult, due to imprecise criteria for the morphological definition of blasts and promyelocytes. An International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) of hematopathologists and hematologists expert in the field of myelodysplastic syndrome reviewed the morphological features of bone marrows from all subtypes of myelodysplastic syndrome and agreed on a set of recommendations, including recommendations for the definition and enumeration of blast cells and ring sideroblasts. It is recommended that (1) agranular or granular blast cells be defined (replacing the previous type I, II and III blasts), (2) dysplastic promyelocytes be distinguished from cytologically normal promyelocytes and from granular blast cells, (3) sufficient cells be counted to give a precise blast percentage, particularly at thresholds that are important for diagnosis or prognosis and (4) ring sideroblasts be defined as erythroblasts in which there are a minimum of 5 siderotic granules covering at least a third of the nuclear circumference. Clear definitions and a differential count of a sufficient number of cells is likely to improve precision in the diagnosis and classification of myelodysplastic syndrome. Recommendations should be applied in the context of the WHO classification.

肺転移を伴う骨肉腫症例に対する外科的肺転移巣切除の意義　　　　　　　　　　　　　　　
中村 晃子, 松藤 凡, 平林 健, 小川 千登世, 真部 淳, 細谷 亮太
小児がん, 45, プログラム・総会号, 317, 317, (NPO)日本小児がん学会, 2008年11月
日本語

自家および同種造血幹細胞移植を含む集学的治療を行った右胸壁原発PNETの一例　　　　　　　　　　　　　　　
神谷 尚宏, 真部 淳, 小川 千登世, 有馬 慶太郎, 平林 真介, 長谷川 大輔, 河守 次郎, 関口 建次, 中村 晃子, 松藤 凡, 細谷 亮太
小児がん, 45, プログラム・総会号, 400, 400, (NPO)日本小児がん学会, 2008年11月
日本語

ALL標準危険群に対するTCCSG治療戦略の変遷 TCCSG ALL L-89-12,92-13,95-14,99-15研究　　　　　　　　　　　　　　　
康 勝好, 小原 明, 磯山 恵一, 梶原 道子, 小池 和俊, 金澤 崇, 嶋田 博之, 田中 竜平, 熊谷 昌明, 木下 明俊, 杉田 完爾, 杉田 憲一, 真部 淳, 林 泰秀, 前田 美穂, 花田 良二, 土田 昌宏
小児がん, 45, プログラム・総会号, 189, 189, (NPO)日本小児がん学会, 2008年11月
日本語

東京小児がん研究グループ(TCCSG)急性リンパ性白血病(ALL)マーカー中央診断におけるT-ALLのマーカー解析　　　　　　　　　　　　　　　
恩田 恵子, 清河 信敬, 藤本 純一郎, 齋藤 正博, 大喜多 肇, 梶原 道子, 福島 敬, 犬飼 岳史, 牧本 敦, 真部 淳, 康 勝好, 中川 温子, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏
小児がん, 45, プログラム・総会号, 190, 190, (NPO)日本小児がん学会, 2008年11月
日本語

小児急性リンパ性白血病に対する寛解導入療法・早期強化療法の安全性に関する検討 TCCSG L04-16研究　　　　　　　　　　　　　　　
小嶋 靖子, 太田 節雄, 牧本 敦, 小原 明, 福島 啓太郎, 福島 敬, 犬飼 岳史, 秋山 政晴, 子川 和宏, 矢部 普正, 康 勝好, 清河 信敬, 真部 淳, 林 泰秀, 花田 良二, 土田 昌宏, 東京小児がん研究グループALL委員会・支持療法委員会
小児がん, 45, プログラム・総会号, 194, 194, (NPO)日本小児がん学会, 2008年11月
日本語

小児急性リンパ性白血病標準危険群治療における入院期間の後方視的検討　　　　　　　　　　　　　　　
望月 慎史, 菊地 陽, 後藤 裕明, 太田 節雄, 富澤 大輔, 廣瀬 衣子, 加藤 陽子, 前田 美穂, 磯山 恵一, 小原 明, 真部 淳, 花田 良二, 土田 昌宏
小児がん, 45, プログラム・総会号, 193, 193, (NPO)日本小児がん学会, 2008年11月
日本語

小児がん経験者のPosttraumatic stress symptomsの時間経過による変化　　　　　　　　　　　　　　　
小澤 美和, 阿佐美 百合子, 平林 真介, 神谷 尚宏, 長谷川 大輔, 小川 千登勢, 石田 也寸志, 真部 淳, 細谷 亮太
小児がん, 45, プログラム・総会号, 222, 222, (NPO)日本小児がん学会, 2008年11月
日本語

化学療法施行に際してClostridium difficile関連下痢症を発症した6例の検討　　　　　　　　　　　　　　　
吉田 健一, 長谷川 大輔, 笠井 恵美, 山本 剛士, 中島 健太郎, 比嘉 千明, 平林 真介, 有馬 慶太郎, 神谷 尚宏, 小川 千登世, 稲井 郁子, 小澤 美和, 真部 淳, 細谷 亮太
小児がん, 45, プログラム・総会号, 249, 249, (NPO)日本小児がん学会, 2008年11月
日本語

小児がん患者における知的発達のフォローアップ　　　　　　　　　　　　　　　
渡辺 静, 阿佐美 百合子, 真部 淳, 長谷川 大輔, 小川 千登世, 小澤 美和, 石田 也寸志, 木津 純子, 細谷 亮太
小児がん, 45, プログラム・総会号, 254, 254, (NPO)日本小児がん学会, 2008年11月
日本語

医療従事者のグリーフケアについての検討　　　　　　　　　　　　　　　
山本 光映, 永瀬 恭子, 宮坂 真紗規, 中村 かおり, 吉川 久美子, 阿佐美 百合子, 小川 千登世, 小澤 美和, 真部 淳, 細谷 亮太
小児がん, 45, プログラム・総会号, 257, 257, (NPO)日本小児がん学会, 2008年11月
日本語

germ cell tumorに対する治療終了から3年後に発症したglioblastomaの症例　　　　　　　　　　　　　　　
比嘉 千明, 中島 健太郎, 有馬 慶太郎, 平林 真介, 長谷川 大輔, 小川 千登世, 真部 淳, 小澤 美和, 関口 建次, 細谷 亮太, 伊藤 昌徳
小児がん, 45, プログラム・総会号, 293, 293, (NPO)日本小児がん学会, 2008年11月
日本語

川崎病と同時に発症したMyeloid/NK前駆細胞性急性白血病の例　　　　　　　　　　　　　　　
有馬 慶太郎, 真部 淳, 吉田 健一, 平林 真介, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 小澤 美和, 海老原 康博, 土屋 恵司, 細谷 亮太
小児がん, 45, プログラム・総会号, 301, 301, (NPO)日本小児がん学会, 2008年11月
日本語

小児がん経験者の身体的晩期合併症 身長と体重に対する検討　　　　　　　　　　　　　　　
小松 なぎさ, 吉田 健一, 中島 健太郎, 平林 真介, 有馬 慶太郎, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 小澤 美和, 真部 淳, 石田 也寸志, 細谷 亮太
小児がん, 45, プログラム・総会号, 380, 380, (NPO)日本小児がん学会, 2008年11月
日本語

Successful Reduction of Cranial Irradiation in Children with B Cell Precursor Acute Lymphoblastic Leukemia(ALL) through Four Consecutive ALL Studies: Long-Term Follow-up of ALL in Tokyo Children's Cancer Study Group (TCCSG) L89-12, 92-13, 95-14 and 99-15 Studies
Chitose Ogawa, Akira Ohara, Atsushi Manabe, Akira Kikuchi, Katsuyoshi Koh, Daisuke Tomizawa, Junya Fujimura, Hiroyasu Inoue, Syosuke Sunami, Eizaburo Ishii, Masaaki Shiohara, Tetsuya Mori, Hiroyuki Takahashi, Yasuhide Hayashi, Ryoji Hanada, Masahiro Tsuchida
BLOOD, 112, 11, 338, 339, AMER SOC HEMATOLOGY, 2008年11月, ［査読有り］
英語

Myelodysplastic Syndrome (MDS) and Myeloproliferative Disease (MPD) in Children: A Prospective Registration of 222 Cases
Shinsuke Hirabayashi, Atsushi Manabe, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Atsuko Masunaga, Ayami Yoshimi, Masafumi Ito, Akira Kikuchi, Kohichiro Tsuji, Akira Ohara, Seiji Kojima, Tatsutoshi Nakahata
BLOOD, 112, 11, 926, 926, AMER SOC HEMATOLOGY, 2008年11月, ［査読有り］
英語

[Pediatric hematology for internists].
Manabe A
[Rinsho ketsueki] The Japanese journal of clinical hematology, 49, 10, 1341, 1348, 2008年10月, ［査読有り］

Mutation analysis of SIPA1 in patients with juvenile myelomonocytic leukemia
Hugues de lavallade, Philippe A. Cassier, Reda Bouabdallah, Jean El-Cheikh, Catherine Faucher, Sabine Fuerst, Diane Coso, Danielle Sainty, Christine Arnoulet, Jean-Albert Gastaut, Bruno Chetaille, Luc Xerri, Didier Blaise, Mohamad Mohty
BRITISH JOURNAL OF HAEMATOLOGY, 142, 5, 850, 851, WILEY-BLACKWELL, 2008年09月, ［査読有り］
英語

小児急性リンパ性白血病におけるDay8ITの意義 東京小児がん研究グループ(TCCSG)L99-15研究より　　　　　　　　　　　　　　　
長谷川 大輔, 真部 淳, 小原 明, 富澤 大輔, 康 勝好, 小川 千登世, 花田 良二, 土田 昌宏
臨床血液, 49, 9, 921, 921, (一社)日本血液学会-東京事務局, 2008年09月
日本語

小児ALLに対する化学療法早期の有効性と安全性の検討 TCCSG ALL L04-16研究　　　　　　　　　　　　　　　
小原 明, 真部 淳, 牧本 敦, 康 勝好, 小川 千登世, 磯山 恵一, 杉田 憲一, 杉田 完爾, 野口 靖, 太田 節雄, 前田 美穂, 矢部 普正, 金子 隆, 熊谷 昌明, 梶原 道子, 高橋 浩之, 菊地 陽, 嶋田 博之, 外松 学, 福島 敬, 齋藤 正博, 林 泰秀, 花田 良二, 土田 昌宏
臨床血液, 49, 9, 921, 921, (一社)日本血液学会-東京事務局, 2008年09月
日本語

高密度SNPマイクロアレイを用いた本邦の小児急性リンパ芽球性白血病のmolecular karyotyping　　　　　　　　　　　　　　　
清河 信敬, 加藤 元博, 藤本 純一郎, 宮川 世志幸, 恩田 恵子, 大喜多 肇, 齋藤 正博, 牧本 敦, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏, 小川 誠司
臨床血液, 49, 9, 1203, 1203, (一社)日本血液学会-東京事務局, 2008年09月
日本語

Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group Study L99-15
Atsushi Manabe, Akira Ohara, Daisuke Hasegawa, Katsuyoshi Koh, Tomohiro Saito, Nobutaka Kiyokawa, Akira Kikuchi, Hiroyuki Takahashi, Koichiro Ikuta, Yasuhide Hayashi, Ryoji Hanada, Masahiro Tsuchida
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 93, 8, 1155, 1160, FERRATA STORTI FOUNDATION, 2008年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Background
Treatment response has become one of the most important prognostic factors in childhood acute lymphoblastic leukemia. We evaluated the significance of the complete clearance of peripheral leukemic blasts on survival in children with acute lymphoblastic leukemia.
Design and Methods
Seven hundred and fifty-four children diagnosed with acute lymphoblastic leukemia, consecutively enrolled from 1999 to 2003 in the TCCSG L99-15 study, were eligible for analysis. Patients were stratified into three risk groups based on presenting features, such as age and the leukocyte count before starting the treatment, followed by reclassification into three categories 7 days after prednisolone monotherapy based on the peripheral blast count; 0/mu L (Day8NoBlasts), 1-999/mu L and >= 1,000/mu L.
Results
After 7 days of prednisolone monotherapy, 249 patients (33%) were classified as Day8NoBlasts, 392 patients (52%) had blast counts of 1-999/mu L, and 113 patients (15%) had blast counts >= 1,000/mu L. The event-free survival for all patients was 79.6 +/- 1.6 (SE)% at 4 years, whereas that for patients with Day8NoBlasts was 90.4 +/- 2.0% (n=249) and the event-free survival for the other patients was 74.2 +/- 2.2% (n=504) (log rank p < 0.001). The event-free survival for Day8NoBlasts patients with B-lineage acute lymphoblastic leukemia and T-cell acute lymphoblastic leukemia was 89.8 +/- 2.1% (n=226) and 95.7 +/- 4.3% (n=23), respectively. In a multivariate analysis, age at diagnosis, the initial white blood cell count, immunophenotype, and gender did not remain as independent risk factors for treatment failure, whereas Day8NoBlasts and marked hyperdiploidy (more than 50 chromosomes) became statistically significant.
Conclusions
Children with Day8NoBlasts constituted one third of all the cases with childhood acute lymphoblastic leukemia with an excellent outcome, and should be candidates for curative management with less intensive treatment.

Mutation analysis of AML1 gene in pediatric primary myelodysplastic syndrome and juvenile myelomonocytic leukemia
Atsuko Masunaga, Toshiyuki Mitsuya, Tsuyoki Kadoftiku, Sanju Iwamoto, Akira Miyazaki, Atsushi Manabe, Yuji Zaike, Masahiro Tsuchida, Tatsutoshi Nakahata
LEUKEMIA RESEARCH, 32, 6, 995, 997, PERGAMON-ELSEVIER SCIENCE LTD, 2008年06月, ［査読有り］
英語

小児がんの治療における中枢神経障害の検討.　　　　　　　　　　　　　　　
渡辺静, 阿佐美百合子, 真部淳, 小川千登世, 長谷川大輔, 小澤美和, 木津純子, 井上忠夫, 細谷亮太
日本小児がん学会雑誌, 45(2), 45(2), 2008年06月, ［査読有り］
日本語, 研究論文（研究会，シンポジウム資料等）

Picture in Clinical Hematology No. 25
平林 真介, 吉田 健一, 中島 健太郎, 有馬 慶太郎, 長谷川 大輔, 小川 千登世, 真部 淳, 細谷 亮太
臨床血液 = The Japanese Journal of Clinical Hematology, 49, 3, 139, 139, The Japanese Society of Hematology, 2008年03月30日
日本語

Iodine-131-metaiodobenzyguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma
Hiroka Takahashi, Atsushi Manabe, Chiaki Aoyama, Takahiro Kamiya, Itaru Kato, Ayako Takusagawa, Chitose Ogawa, Miwa Ozawa, Ryota Hosoya, Kunihiko Yokoyama
PEDIATRIC BLOOD & CANCER, 50, 3, 676, 678, WILEY-LISS, 2008年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stein cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant Course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.

Desmoplastic small round cell tumorが疑われた縦隔肉腫の乳児例
平林 真介, 青山 千晶, 伊藤 雄伍, 今村 壽宏, 加藤 格, 神谷 尚宏, 藤田 真智子, 小澤 美和, 真部 淳, 細谷 亮太, 森本 克, 松藤 凡, 鈴木 高祐, 田中 祐吉, 秦 順一
小児がん, 45, 1, 36, 40, (NPO)日本小児がん学会, 2008年02月
日本語, 生後3ヵ月女児。呼吸困難を主訴に来院、精査にて左縦隔に巨大腫瘤を認めた。生検を行い、Desmoplastic small round cell tumor(DSRCT)と診断された。化学療法にて腫瘍は縮小傾向を示したが、水頭症を発症、頸椎への浸潤と髄膜播種の所見が認められた。VPシャント挿入後、末梢血幹細胞移植を含む化学療法を施行したが、不幸な転帰を辿った。極めて稀な縦隔原発DSRCTの乳児例を報告する。(著者抄録)

小児がん経験者のsexualityを支援するフォローアップ外来を立ち上げて　　　　　　　　　　　　　　　
巷岡 彩子, 小澤 美和, 鈴木 麻水, 塩田 恭子, 佐藤 孝道, 有馬 慶太郎, 平林 真介, 小川 千登世, 真部 淳, 細谷 亮太
日本小児科学会雑誌, 112, 2, 278, 278, (公社)日本小児科学会, 2008年02月
日本語

聖路加国際病院小児科レジデント教育の現況(第13報) 電子カルテが教育へ及ぼす影響　　　　　　　　　　　　　　　
有馬 慶太郎, 平林 真介, 中川 真智子, 長谷川 大輔, 小川 千登世, 稲井 郁子, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 112, 2, 329, 329, (公社)日本小児科学会, 2008年02月
日本語

Wiskott-Aldrich syndrome is an important differential diagnosis in male infants with juvenile myelomonocytic leukemialike features
Nobuhiro Watanabe, Ayami Yoshimi, Yoshiro Kamachi, Takashi Kawabe, Hideki Muramatsu, Kimikazu Matsumoto, Atsushi Manabe, Seiji Kojima, Koji Kato
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 29, 12, 836, 838, LIPPINCOTT WILLIAMS & WILKINS, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）, A newborn presented with thrombocytopenia at birth and subsequently developed leukocytosis, monocytosis, and mild hepatomegaly. The bone marrow was normocellular with dysplasia and spontaneous granulocyte-monocyte colony formation was demonstrated. These findings fulfilled the diagnostic criteria of juvenile myelomonocytic leukemia. Then he developed atopic dermatitislike eczema, which led to the consideration of Wiskott-Aldrich syndrome (WAS). Lack of intracellular WASP expression and WASP gene mutation confirmed the diagnosis of WAS. After stem cell transplantation, he is alive in good condition with normal WASP expression. WAS should be considered as a differential diagnosis in male infants with juvenile myelomonocytic leukemialike features.

The effect of donor leukocyte infusion on refractory pure red blood cell aplasia after allogeneic stem cell transplantation in a patient with myelodysplastic syndrome developing from Kostmann syndrome
Yasuhiro Ebihara, Atsushi Manabe, Toshihisa Tsuruta, Kumiko Ishikawa, Daisuke Hasegawa, Yoshitoshi Ohtsuka, Hirohide Kawasaki, Kazuo Ogami, Yuka Wada, Tadayasu Kanda, Kohichiro Tsuji
INTERNATIONAL JOURNAL OF HEMATOLOGY, 86, 5, 446, 450, SPRINGER TOKYO, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）, We describe the clinical course of a patient who experienced refractory pure red cell aplasia (PRCA) after undergoing HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for refractory anemia with an excess of blasts in transformation that had evolved from Kostmann syndrome. The treatment for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) developing from Kostmann syndrome has not been standardized. We treated this patient with allo-PBSCT using a regimen combining high-dose cytosine arabinoside with granulocyte colony-stimulating factor, in addition to total body irradiation and cyclophosphamide without preceding intensive chemotherapy. The donor was ABO incompatible. Myeloid and platelet recoveries were achieved rapidly. Erythroid engraftment was not evident, however, and the patient was given a diagnosis of PRCA. Regimen-related toxicity and graft-versus-host disease (GVHD) were limited. The PRCA did not respond to various therapies, including the discontinuation of immunosuppressants for the induction of chronic GVHD, human recombinant erythropoietin, immunosuppressive treatment with steroids, cyclosporin A, and human anti-CD20 antibody (rituximab). The patient received transfusions 48 times until the resolution of his anemia by donor leukocyte infusion (DLI) at 25 months after PBSCT. He is now clinically well (performance status, 100%) with normal blood cell counts at 5 years after SCT An in vitro study demonstrated that serum from the recipient blocked the differentiation of erythroid cells in the bone marrow. The results indicate that the conditioning regimen we describe seems safe and effective for those who have MDS/AML and that DLI might be a valuable approach for refractory PRCA after ABO-incompatible SCT.

小児Castleman病の2例　　　　　　　　　　　　　　　
有馬 慶太郎, 稲井 郁子, 真部 淳, 長谷川 大輔, 小川 千登世, 細谷 亮太, 荒木 夕宇子, 中村 晃子, 松藤 凡, 竹内 敏雄, 三輪 操子, 上松 一永
小児感染免疫, 19, 4, 490, 490, (一社)日本小児感染症学会, 2007年12月
日本語

自家末梢血幹細胞移植後に消化管出血、VOD、肺出血を来たし死亡した神経芽腫の1例　　　　　　　　　　　　　　　
吉田 健一, 長谷川 大輔, 平林 真介, 有馬 慶太郎, 小川 千登世, 真部 淳, 中村 晃子, 松藤 凡, 細谷 亮太
小児がん, 44, プログラム・総会号, 237, 237, (NPO)日本小児がん学会, 2007年12月
日本語

肺転移を伴ったWilms腫瘍に対して治療終了のタイミングを開胸肺生検で決定した2例についての検討　　　　　　　　　　　　　　　
中村 晃子, 松藤 凡, 平林 健, 小川 千登世, 真部 淳, 細谷 亮太
小児がん, 44, プログラム・総会号, 356, 356, (NPO)日本小児がん学会, 2007年12月
日本語

診断に難渋した左上顎洞腫瘍の1女児例　　　　　　　　　　　　　　　
苛原 香, 真部 淳, 小川 千登世, 長谷川 大輔, 田草川 彩子, 高橋 宏佳, 今西 康次, 有馬 慶太郎, 平林 真介, 細谷 亮太, 中村 晃子, 荒木 夕宇子, 松藤 凡, 鈴木 高祐, 岸本 誠司
小児がん, 44, プログラム・総会号, 367, 367, (NPO)日本小児がん学会, 2007年12月
日本語

急性リンパ性白血病の染色体・遺伝子異常と予後 TCCSG ALL L95-14・L99-15研究　　　　　　　　　　　　　　　
高橋 浩之, 小原 明, 齋藤 正博, 福島 敬, 梶原 道子, 小嶋 靖子, 菊地 陽, 小川 千登世, 前田 美穂, 塩原 正明, 康 勝好, 真部 淳, 林 泰秀, 花田 良二, 土田 昌宏, 東京小児がん研究グループ(TCCSG)ALL委員会
小児がん, 44, プログラム・総会号, 179, 179, (NPO)日本小児がん学会, 2007年12月
日本語

東京小児がん研究グループALL治療第16次研究(TCCSG L04-16/06-16)におけるマーカー中央診断　　　　　　　　　　　　　　　
清河 信敬, 藤本 純一郎, 田口 智子, 塩沢 裕介, 斉藤 洋平, 大喜多 肇, 梶原 道子, 福島 敬, 河崎 裕英, 犬飼 岳史, 牧本 敦, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏
小児がん, 44, プログラム・総会号, 180, 180, (NPO)日本小児がん学会, 2007年12月
日本語

1歳の小児急性リンパ性白血病の臨床像及び治療成績の検討 東京小児がん研究グループ(TCCSG)からの報告　　　　　　　　　　　　　　　
富澤 大輔, 磯山 恵一, 小原 明, 福島 啓太郎, 金子 隆, 加藤 陽子, 野口 靖, 太田 節雄, 嶋田 博之, 矢部 普正, 康 勝好, 真部 淳, 林 泰秀, 花田 良二, 土田 昌宏
小児がん, 44, プログラム・総会号, 172, 172, (NPO)日本小児がん学会, 2007年12月
日本語

骨・軟部腫瘍患児の術前/術後の面接から疾患の受け止め方を考える　　　　　　　　　　　　　　　
小澤 美和, 阿佐美 百合子, 有馬 慶太郎, 平林 真介, 長谷川 大輔, 小川 千登勢, 真部 淳, 細谷 亮太
小児がん, 44, プログラム・総会号, 206, 206, (NPO)日本小児がん学会, 2007年12月
日本語

小児がん患者長期フォローアップの実践 当院の最近20年間の実態調査　　　　　　　　　　　　　　　
渡辺 静, 真部 淳, 長谷川 大輔, 小川 千登世, 小澤 美和, 井上 忠夫, 木津 純子, 森本 克, 西村 昴三, 細谷 亮太
小児がん, 44, プログラム・総会号, 245, 245, (NPO)日本小児がん学会, 2007年12月
日本語

Acute myeloid leukemia with multifineage dysplasia in children
Souichi Adachi, Atsushi Manabe, Masue Imaizumi, Takashi Taga, Akio Tawa, Masahito Tsurusawa, Akira Kikuchi, Atsuko Masunaga, Masahiro Tsuchida, Tatsutoshi Nakahata
INTERNATIONAL JOURNAL OF HEMATOLOGY, 86, 4, 358, 363, SPRINGER TOKYO, 2007年11月, ［査読有り］
英語, 研究論文（学術雑誌）, We retrospectively surveyed pediatric acute myeloid leukemia (AML) patients with multilineage dysplasia treated with the AML 99 and the Children's Cancer and Leukemia Study Group (CCLSG) AML 9805 protocols. We found only 9 AML patients (2.6%) with multilineage dysplasia among the 341 patients with newly diagnosed de novo AML. Eight of the 9 patients obtained complete remission (CR) following the intensive AML-oriented treatments. Three of 7 patients who underwent stem cell transplantation were alive in CR for more than 4 years, and the 2 patients treated only with chemotherapy were alive in CR for more than 30 months. We did not identify any particular chromosomal abnormalities or differentiation according to the French-American-British classification in these 9 patients. No reports have described AML with multilineage dysplasia in children, and the incidence of the disease is expected to be very low. We plan to conduct a prospective pathologic review to select cases with this disease entity in the next Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol.

上顎洞原発粘液性軟骨肉腫の1女児例
苛原 香, 真部 淳, 小川 千登世, 平林 真介, 田草川 彩子, 高橋 宏佳, 今西 康次, 有賀 慶太郎, 長谷川 大輔, 細谷 亮太, 中村 晃子, 荒木 夕宇子, 松藤 凡, 鈴木 高祐, 岸本 誠司
小児がん, 44, 2, 198, 198, (NPO)日本小児がん学会, 2007年09月
日本語

TCCSG L95-14およびL99-15にて治療後に再発した小児急性リンパ性白血病の予後　　　　　　　　　　　　　　　
小川 千登世, 康 勝好, 金子 隆, 後藤 裕明, 太田 節雄, 真部 淳, 小原 明, 花田 良二, 土田 昌宏
臨床血液, 48, 9, 936, 936, (一社)日本血液学会-東京事務局, 2007年09月
日本語

小児がん経験者のsexualityを支援するfollow up外来を立ち上げて　　　　　　　　　　　　　　　
巷岡 彩子, 小澤 美和, 鈴木 麻水, 塩田 恭子, 佐藤 孝道, 有馬 慶太郎, 長谷川 大輔, 小川 千登世, 真部 淳, 細谷 亮太
臨床血液, 48, 9, 975, 975, (一社)日本血液学会-東京事務局, 2007年09月
日本語

小児Castleman病の2例　　　　　　　　　　　　　　　
有馬 慶太郎, 稲井 郁子, 真部 淳, 平林 真介, 高橋 宏佳, 田草川 彩子, 長谷川 大輔, 小川 千登世, 荒木 夕宇子, 中村 晃子, 松藤 凡, 細谷 亮太, 竹内 敏雄, 三輪 操子, 上松 一永
日本小児科学会雑誌, 111, 7, 912, 912, (公社)日本小児科学会, 2007年07月
日本語

小児がん患児のきょうだいにおける心理的問題の検討
小澤 美和, 泉 真由子, 森本 克, 真部 淳, 細谷 亮太
日本小児科学会雑誌, 111, 7, 847, 854, (公社)日本小児科学会, 2007年07月
日本語, 小児がん患児のきょうだい23人を対象に、心理的な現状を知るため、きょうだい自身のself-reportを用いた面接調査を行った。きょうだいへは、特性不安検査、ソーシャルサポート授与感、バウムテスト、ベンダーベシュタルトテストを行い、母親へはきょうだいの背景について問う質問紙とTS式幼児・児童性格診断を行った。その結果、きょうだいは、小児がん患児や慢性疾患々児らと同等で、とくに不安が高い集団ではなかった。誰からのソーシャルサポートを実感しているかという項目に注目すると、きょうだいは、先生や友人からのサポートを患児よりもより高く実感していた。投影法によると、生活年齢に比して理性よりも感情優位の状況であり、心理学的には年齢相当の成長をしていないことが示唆された。更に、精神的エネルギーが少なく、自己存在感が乏しいことがわかった。また、ベンダーゲシュタルトテストから抽出された彼らの情緒指標から、約2分の1のきょうだいたちは精神的に混乱し、情緒不安定な状態であり、約4分の1が逸脱行動をとる可能性が示された。しかし、親から観察されるきょうだいの情動、対人関係、体質についてはすべて年齢相当で問題ないと評価されており、親は患児のことで頭がいっぱいで、きょうだいの不安定感や行動の問題などに気づいていない傾向が示された。

Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations
Kazuyuki Matsuda, Akira Shimada, Nao Yoshida, Atsushi Ogawa, Akihiro Watanabe, Shuhei Yajima, Susumu Iizuka, Kazutoshi Koike, Fumio Yanai, Keiichiro Kawasaki, Masakatsu Yanagimachi, Akira Kikuchi, Yoshitoshi Ohtsuka, Eiko Hidaka, Kazuyoshi Yamauchi, Miyuki Tanaka, Ryu Yanagisawa, Yozo Nakazawa, Masaaki Shiohara, Atsushi Manabe, Seiji Kojima, Kenichi Koike
BLOOD, 109, 12, 5477, 5480, AMER SOC HEMATOLOGY, 2007年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoletic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMMIL with specific RAS mutations may have spontaneously improving disease.

当科で経験したOncologic surgical emergencyについての検討　　　　　　　　　　　　　　　
中村 晃子, 松藤 凡, 荒木 夕宇子, 真部 淳, 草川 功, 細谷 亮太
日本小児救急医学会雑誌, 6, 1, 116, 116, (一社)日本小児救急医学会, 2007年06月
日本語

Development of diffuse large B cell lymphoma during the maintenance therapy for B-lineage acute lymphoblastic leukemia
Itaru Kato, Atsushi Manabe, Chiaki Aoyama, Takahiro Kamiya, Tsuyoshi Morimoto, Hiroshi Matsufuji, Koyu Suzuki, Yoshiro Kitagawa, Toshinori Hori, Masahito Tsurusawa, Nobutaka Kiyokawa, Junichiro Fujimoto, Ryota Hosoya
PEDIATRIC BLOOD & CANCER, 48, 2, 230, 232, WILEY-LISS, 2007年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Non-Hodgkin lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). A Japanese boy presented with B-lineage ALL at the age of 2.5. He was treated with chemotherapy for standard-risk ALL. While he was receiving maintenance treatment 2 years and 9 months after the diagnosis of ALL, diffuse large B cell lymphoma(DLBL) was diagnosed from a biopsy of an abdominal mass. DLBL was treated by surgical resection followed by chemotherapy for 6 months. The patient has been free from the recurrence of ALL or DLBL for 16 months after the development of DLBL.

小児Castleman病の2例　　　　　　　　　　　　　　　
有馬 慶太郎, 稲井 郁子, 真部 淳, 小川 千登世, 荒木 夕宇子, 松藤 凡, 竹内 敏雄, 三輪 操子, 上松 一永, 細谷 亮太
日本小児科学会雑誌, 111, 2, 249, 249, (公社)日本小児科学会, 2007年02月
日本語

聖路加国際病院小児科レジデント教育の現況(第12報) 新臨床研修制度への対応　　　　　　　　　　　　　　　
今村 壽宏, 有馬 慶太郎, 平林 真介, 高橋 宏佳, 田草川 彩子, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 111, 2, 316, 316, (公社)日本小児科学会, 2007年02月
日本語

Immunosuppressive therapy in children with refractory anemia: Results of Japanese childhood MDS study group trial (MDS99).
Daisuke Hasegawa, Hiroshi Yagasaki, Yoshitoshi Ohtsuka, Masami Inoue, Akira Kikuchi, Akira Ohara, Masahiro Tsuchida, Seiji Kojima, Atsushi Manabe, Tatsutoshi Nakahata
BLOOD, 108, 11, 756A, 756A, AMER SOC HEMATOLOGY, 2006年11月, ［査読有り］
英語

健常腎温存のための治療方針選択に苦慮した、両側ウィルムス腫瘍(stage V,FRN)の1例　　　　　　　　　　　　　　　
荒木 夕宇子, 松藤 凡, 中村 晃子, 細谷 亮太, 真部 淳, 小川 千登世
日本小児血液学会雑誌, 20, 5, 332, 332, 日本小児血液学会, 2006年10月
日本語

当院で経験したユーイング肉腫ファミリー腫瘍10例の治療についての検討　　　　　　　　　　　　　　　
中村 晃子, 松藤 凡, 荒木 夕宇子, 道川 武紘, 小川 千登世, 真部 淳, 細谷 亮太
日本小児血液学会雑誌, 20, 5, 402, 402, 日本小児血液学会, 2006年10月
日本語

下大静脈合併切除を行ったStageIVのWilms腫瘍　　　　　　　　　　　　　　　
道川 武紘, 松藤 凡, 荒木 夕宇子, 中村 晃子, 小川 千登世, 真部 淳, 細谷 亮太
日本小児血液学会雑誌, 20, 5, 411, 411, 日本小児血液学会, 2006年10月
日本語

TEL/AML1陽性急性リンパ性白血病におけるday15BM芽球比率の重要性　　　　　　　　　　　　　　　
野口 靖, 小原 明, 真部 淳, 太田 節雄, 高橋 浩之, 福島 啓太郎, 杉田 憲一, 小川 千登世, 菊池 陽, 康 勝好, 生田 孝一郎, 林 泰秀, 花田 良二, 土田 昌宏
日本小児血液学会雑誌, 20, 5, 500, 500, 日本小児血液学会, 2006年10月
日本語

TCCSG L95-14およびL99-15にて治療後に再発した小児急性リンパ性白血病の予後　　　　　　　　　　　　　　　
小川 千登世, 康 勝好, 金子 隆, 太田 節雄, 後藤 裕明, 真部 淳, 小原 明, 花田 良二, 土田 昌宏
日本小児血液学会雑誌, 20, 5, 505, 505, 日本小児血液学会, 2006年10月
日本語

急性リンパ性白血病標準危険群・中間危険群に対する6MP/MTX漸増間歇維持療法の有効性の検討　　　　　　　　　　　　　　　
外松 学, 小原 明, 真部 淳, 金子 隆, 前田 美穂, 中舘 尚也, 福島 敬, 熊谷 昌明, 三浦 信之, 加藤 陽子, 生田 孝一郎, 林 泰秀, 花田 良二, 土田 昌宏, 東京小児がん研究グループ
日本小児血液学会雑誌, 20, 5, 360, 360, 日本小児血液学会, 2006年10月
日本語

最近当院で経験した骨肉腫の10症例　　　　　　　　　　　　　　　
田草川 彩子, 真部 淳, 加藤 格, 高橋 宏佳, 今村 壽宏, 有馬 慶太郎, 平林 真介, 長谷川 大輔, 小林 明雪子, 小川 千登世, 小澤 美和, 細谷 亮太, 真鍋 淳, 松本 誠一, 川口 智義
日本小児血液学会雑誌, 20, 5, 398, 398, 日本小児血液学会, 2006年10月
日本語

小児期に発症し、成人に持ち越した急性リンパ性白血病の2症例　　　　　　　　　　　　　　　
高橋 宏佳, 小澤 美和, 田草川 彩子, 長谷川 大輔, 小川 千登世, 真部 淳, 細谷 亮太, 塚崎 百合子, 西田 知佳子
日本小児血液学会雑誌, 20, 5, 425, 425, 日本小児血液学会, 2006年10月
日本語

小児悪性腫瘍患者における中枢神経障害の検討　　　　　　　　　　　　　　　
渡辺 静, 塚崎 百合子, 田草川 彩子, 長谷川 大輔, 小林 明雪子, 小川 千登世, 小澤 美和, 真部 淳, 細谷 亮太, 井上 忠夫, 木津 純子
日本小児血液学会雑誌, 20, 5, 435, 435, 日本小児血液学会, 2006年10月
日本語

心タンポナーデを合併したリンパ管腫症の1例　　　　　　　　　　　　　　　
田草川 彩子, 小川 千登世, 高橋 宏佳, 加藤 格, 今村 壽宏, 小澤 美和, 真部 淳, 細谷 亮太
日本小児血液学会雑誌, 20, 5, 454, 454, 日本小児血液学会, 2006年10月
日本語

東京小児がん研究グループTCCSG小児急性リンパ性白血病プロトコールALL L99-15研究中間解析　　　　　　　　　　　　　　　
小原 明, 真部 淳, 康 勝好, 磯山 恵一, 杉田 憲一, 杉田 完爾, 太田 節雄, 沖本 由理, 木下 明俊, 前田 美穂, 矢部 普正, 金子 隆, 熊谷 昌明, 上條 岳彦, 梶原 道子, 高橋 浩之, 菊地 陽, 小川 千登世, 外松 学, 福島 敬, 齋藤 正博, 別所 文雄, 生田 孝一郎, 齋藤 友博, 林 泰秀, 花田 良二, 土田 昌宏, 東京小児がん研究グループ
臨床血液, 47, 9, 1013, 1013, (一社)日本血液学会-東京事務局, 2006年09月
日本語

小児ALLにおけるPred反応性最良好群(Day8末梢血芽球ゼロ)の治療成績 TCCSG L99-15研究　　　　　　　　　　　　　　　
真部 淳, 小原 明, 康 勝好, 太田 節雄, 小川 千登世, 加藤 陽子, 後藤 裕明, 齋藤 正博, 嶋田 博之, 高橋 浩之, 富沢 大輔, 中舘 尚也, 野口 靖, 福島 啓太郎, 福島 敬, 牧本 敦, 三浦 信之, 林 泰秀, 生田 孝一郎, 齋藤 友博, 熊谷 昌明, 花田 良二, 土田 昌宏
臨床血液, 47, 9, 1030, 1030, (一社)日本血液学会-東京事務局, 2006年09月
日本語

初発時hyperleukocytosisをきたしたT cell ALLの3例　　　　　　　　　　　　　　　
田草川 彩子, 真部 淳, 高橋 宏佳, 今村 壽宏, 加藤 格, 神谷 尚宏, 長谷川 大輔, 小林 明雪子, 稲井 郁子, 小川 千登世, 小澤 美和, 細谷 亮太
臨床血液, 47, 9, 1257, 1257, (一社)日本血液学会-東京事務局, 2006年09月
日本語

Picture in Clinical Hematology
真部 淳
臨床血液 = The Japanese Journal of Clinical Hematology, 47, 4, 255, 255, The Japanese Society of Hematology, 2006年04月30日
日本語

Irinotecan for children with relapsed solid tumors
T Shitara, A Shimada, R Hanada, T Matsunaga, K Kawa, H Mugishima, T Sugimoto, JI Mimaya, A Manabe, M Tsurusawa, Y Tsuchida
PEDIATRIC HEMATOLOGY AND ONCOLOGY, 23, 2, 103, 110, TAYLOR & FRANCIS INC, 2006年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen children with relapsed solid tumors received irinotecan 180 mg/m(2)/day for 3 consecutive days, repeated once after 25 days off. Their original tumors were neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in I each. The average age at trials was 6 years. Partial response was achieved in 5 (31.3 %) (neuroblastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2. Irinotecan appears promising, and could become included in the first-line treatment.

聖路加国際病院小児科レジデント教育の現況(第11報) 新臨床研修制度が始まって　　　　　　　　　　　　　　　
神谷 尚宏, 伊藤 雄伍, 今村 寿宏, 加藤 格, 小川 千登世, 稲井 郁子, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 110, 2, 282, 282, (公社)日本小児科学会, 2006年02月
日本語

学童期に経験した親との喪失体験の違いによる受容過程についての考察　　　　　　　　　　　　　　　
小澤 美和, 一ノ橋 祐子, 小川 千登世, 稲井 郁子, 森本 克, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 110, 2, 330, 330, (公社)日本小児科学会, 2006年02月
日本語

P-52 最近10年間に当院で経験した10例のEwing肉腫/pPNETについての検討(示説13 腫瘍2・代謝,第43回 日本小児外科学会総会)
中村 晃子, 松藤 凡, 荒木 夕宇子, 細谷 亮太, 真部 淳
日本小児外科学会雑誌, 42, 3, 445, 445, 特定非営利活動法人 日本小児外科学会, 2006年
日本語

眼窩周囲炎・副鼻腔炎に続発した眼窩蜂窩織炎の1例
加藤 格, 今村 壽宏, 伊藤 雄伍, 神谷 尚宏, 藤田 真智子, 青山 千昌, 安西 有紀, 稲井 郁子, 小澤 美和, 森本 克, 真部 淳, 草川 功, 細谷 亮太, 小暮 朗子, 大越 貴志子, 山口 達夫
小児科臨床, 59, 1, 131, 136, (株)日本小児医事出版社, 2006年01月
日本語, 左眼窩周囲の腫脹を主訴に入院した1歳男児.左眼窩蜂窩織炎の診断にて抗生剤投与開始するものの,左眼窩内の脂肪織に炎症が波及し圧迫による視神経への影響を認めた.外科的処置まで考慮されたが抗生剤の追加投与,ステロイド投与にて症状改善を認めた.年少児の眼窩蜂窩織炎では眼球突出や眼球運動制限といった眼窩内病変によって起こる症状が評価しにくいため,不可逆的な視神経障害を来す前にCT,MRIなどによる速やかな画像検索を行い,的確な治療が必要である(著者抄録)

RAS-blocking bisphosphonate zoledronic acid inhibits the abnormal proliferation and differentiation of juvenile myelomonocytic leukemia cells in vitro
Y Ohtsuka, A Manabe, H Kawasaki, D Hasegawa, Y Zaike, S Watanabe, T Tanizawa, T Nakahata, K Tsuji
BLOOD, 106, 9, 3134, 3141, AMER SOC HEMATOLOGY, 2005年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Juvenile myelomonocytic leukemia (JMML) is a clonal myeloproliferative/myelodysplastic disorder of early childhood with a poor prognosis. JMML cells are characterized by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GMCSF) caused by a continuously activated GM-CSF receptor-retrovirus-associated sequence (RAS) signal transduction pathway through various molecular mechanisms, resulting in spontaneous GM colony formation in vitro. Bisphosphonate zoledronic acid (ZOL), a RAS-blocking compound, suppressed colony formation from bone marrow (BM) cells of 8 patients with JMML and 5 healthy control subjects without and with GM-CSF (10 ng/mL), respectively, in a dose-dependent manner in clonal culture. At 10 mu M ZOL, however, spontaneous GM colony formation from JMML BM cells decreased to 3%, but the formation of G colonies containing granulocytes, but no macrophages, was enhanced, whereas 40% of GM colonies were retained and G colony formation was not affected in culture of normal BM cells with GM-CSF. In suspension culture, cytochemical and flow cytometric analyses showed that 10 mu M ZOL also inhibited spontaneous proliferation and differentiation along monocyte/macrophage lineage of JMML BM cells but not the development of normal BM cells by GM-CSF. The inhibitory effect of ZOL on JMML cells was confirmed at a single-clone level and observed even at 3 mu M. The current result offers a novel approach to therapy in JMML.

眼窩周囲炎・副鼻腔炎に続発した眼窩蜂窩織炎の1例　　　　　　　　　　　　　　　
加藤 格, 今村 壽宏, 伊藤 雄伍, 神谷 尚宏, 藤田 真智子, 青山 千昌, 安西 有紀, 稲井 郁子, 小澤 美和, 森本 克, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 109, 11, 1383, 1383, (公社)日本小児科学会, 2005年11月
日本語

鎖骨に生じたMRSA骨髄炎の1例　　　　　　　　　　　　　　　
平林 真介, 高橋 宏佳, 田草川 彩子, 伊藤 雄伍, 今村 壽宏, 加藤 格, 神谷 尚宏, 一ノ橋 裕子, 小川 千登世, 稲井 郁子, 小澤 美和, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 109, 11, 1390, 1390, (公社)日本小児科学会, 2005年11月
日本語

11th symposium on aplastic anemia and 9th symposium on myelodysplastic syndromes in children
Atsushi Manabe, Seiji Kojima
Pediatrics International, 47, 5, 572, 574, 2005年10月, ［査読有り］
英語, 研究論文（国際会議プロシーディングス）

トータルケアの心と実践 地域共同診療(ウォーターフロント小児がん共同治療計画) 手術,化学療法,移植治療の分担と支援グループの共有　　　　　　　　　　　　　　　
松藤 凡, 荒木 夕宇子, 中村 晃子, 細谷 亮太, 真部 淳, 川口 智義, 高上 洋一, 牧本 敦
日本小児血液学会雑誌, 19, 5, 278, 278, 日本小児血液学会, 2005年10月
日本語

MDSの中央診断 骨髄生検の実施状況　　　　　　　　　　　　　　　
増永 敦子, 在家 裕司, 菅原 幸子, 土田 昌宏, 河崎 裕英, 真部 淳
日本小児血液学会雑誌, 19, 5, 299, 299, 日本小児血液学会, 2005年10月
日本語

小児11q23転座型急性リンパ性白血病(ALL)の第一寛解期移植による治療成績の向上　　　　　　　　　　　　　　　
齋藤 正博, 林 泰秀, 康 勝好, 高橋 浩之, 福島 敬, 太田 節雄, 真部 淳, 杉田 憲一, 杉田 完爾, 矢部 普正, 菊地 陽, 野口 靖, 生田 孝一郎, 小原 明, 花田 良二, 土田 昌宏, 東京小児がん研究グループ(TCCSG)ALL委員会
日本小児血液学会雑誌, 19, 5, 355, 355, 日本小児血液学会, 2005年10月
日本語

CD10陽性T細胞型急性リンパ性白血病(T-ALL)の臨床像および予後　　　　　　　　　　　　　　　
三浦 信之, 真部 淳, 嶋田 博之, 熊谷 昌明, 金子 隆, 前田 美穂, 木下 明俊, 沖本 由理, 加藤 陽子, 上條 岳彦, 豊田 恭徳, 生田 孝一郎, 小原 明, 花田 良二, 土田 昌宏, 東京小児がん研究グループALL委員会
日本小児血液学会雑誌, 19, 5, 500, 500, 日本小児血液学会, 2005年10月
日本語

131I-MIBG療法を2回施行し,良好なQOLを得られた再発神経芽腫の1例　　　　　　　　　　　　　　　
神谷 尚宏, 青山 千晶, 藤田 真智子, 伊藤 雄伍, 今村 壽宏, 加藤 格, 真部 淳, 小川 千登世, 小澤 美和, 細谷 亮太, 横山 邦彦
日本小児血液学会雑誌, 19, 5, 331, 331, 日本小児血液学会, 2005年10月
日本語

No advantage of dexamethasone over prednisolone for the outcome of standard- and intermediate-risk childhood acute lymphoblastic leukemia in the Tokyo Children's Cancer Study Group L95-14 protocol
S Igarashi, A Manabe, A Ohara, M Kumagai, T Saito, Y Okimoto, T Kamijo, K Isoyama, M Kajiwara, M Sotomatsu, K Sugita, K Sugita, M Maeda, H Yabe, A Kinoshita, T Kaneko, Y Hayashi, K Ikuta, R Hanada, M Tsuchida
JOURNAL OF CLINICAL ONCOLOGY, 23, 27, 6489, 6498, AMER SOC CLINICAL ONCOLOGY, 2005年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose To evaluate whether dexamethasone (DEXA) yields a better outcome than prednisolone (PRED) in a prospective, randomized, controlled trial for the treatment of childhood acute lymphoblastic leukemia (ALL).
Patients and Methods Two hundred thirty-one standard-risk (SR) patients and 128 intermediate-risk (IR) non-B-cell ALL patients were registered from March 1995 to March 1999. After random assignment in each group, the PRED arm patients received PRED 60 mg/m(2) during induction followed by PRED 40 mg/m(2) over four intensifications in the SR group and three intensifications in the IR group. DEXA arm patients received DEXA 8 mg/m(2) during induction and DEXA 6 mg/m(2) during the intensifications. The maintenance phase was continued until week 104.
Results Event-free survival rates at 8 years in the DEXA and PRED arms were 81.1% +/- 3.9% (n = 117) and 84.4% +/- 5.2% (n = 114), respectively, in the SR group (P = .217) and 84.9% +/- 4.6% (n = 62) and 80.4% +/- 5.1 % (n = 66), respectively, in the IR group (P = .625). The primary reason for treatment failure was marrow relapse. Only two extramedullary relapses occurred in the DEXA arm compared with seven relapses in the PRED arm. Although complications were more prevalent in the DEXA arm than in the PRED arm, fatal toxicity was rare both groups.
Conclusion DEXA administered at 8 mg/m(2) during induction and 6 mg/m(2) during intensification showed no advantage over PRED administered at 60 mg/m(2) during induction and 40 mg/m(2) during intensification in both the SR and IR groups.

若年性骨髄単球性白血病(JMML)における赤芽球コロニー形成に対するビスフォスフォネート製剤の効果　　　　　　　　　　　　　　　
大塚 欣敏, 浅野 由美, 金田 由美, 竹田 洋樹, 森田 直子, 長谷川 大輔, 河崎 裕英, 真部 淳, 辻 浩一郎, 谷澤 隆邦
日本血液学会・日本臨床血液学会総会プログラム・抄録集, 67回・47回, 824, 824, 日本臨床血液学会, 2005年09月
日本語

小児急性リンパ性白血病(ALL)診断時・寛解導入期にみられる凝固異常と治療の必要性　　　　　　　　　　　　　　　
加藤 格, 神谷 尚宏, 田草川 彩子, 高橋 宏佳, 小澤 美和, 森本 克, 小川 千登世, 真部 淳, 細谷 亮太
日本血液学会・日本臨床血液学会総会プログラム・抄録集, 67回・47回, 750, 750, 日本臨床血液学会, 2005年09月
日本語

海外で処方された睡眠薬により中毒症状を来した1例　　　　　　　　　　　　　　　
今村 壽宏, 伊藤 雄伍, 加藤 格, 神谷 尚宏, 青山 千晶, 藤田 真智子, 安西 有紀, 稲井 郁子, 小澤 美和, 森本 克, 真部 淳, 草川 功, 細谷 亮太
日本小児科学会雑誌, 109, 7, 901, 901, (公社)日本小児科学会, 2005年07月
日本語

脾臓摘出術を行い貧血が改善したCDA Type IIの1例
藤田 真智子, 森本 克, 真部 淳, 小澤 美和, 細谷 亮太
日本小児外科学会雑誌, 41, 4, 712, 712, (一社)日本小児外科学会, 2005年06月
日本語

Therapy-related myelodysplastic syndrome in childhood: A retrospective study of 36 patients in Japan
M Tsurusawa, A Manabe, Y Hayashi, Y Akiyama, H Kigasawa, H Inada, Y Noguchi, N Sawai, R Kobayashi, Y Nagatoshi, K Kawakami, S Kojima, T Nakahata
LEUKEMIA RESEARCH, 29, 6, 625, 632, PERGAMON-ELSEVIER SCIENCE LTD, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, We report here a retrospective analysis of 36 children with therapy-related rnyelodysplastic syndrome (t-MDS) diagnosed between 1990 and 1999 in Japan. Their median age was 7.7 years and the median latency period for the development of t-MDS was 38.5 months. The primary tumors were hematologic in 15 of the cases and nonhematologic in 21. Chromosomal abnormalities were detected in 32/34(94%) patients: abnormalities of chromosomes 5 and/or 7 in 41% and notably. 11q23 abnormalities in 31%. The prognosis of children with t-MDS was very poor as compared to children with primary MDS (5 year survival: 16% versus 54%, p < 0.0001). (c) 2005 Elsevier Ltd. All rights reserved.

Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia
D Hasegawa, A Manabe, T Kubota, H Kawasaki, Hirose, I, Y Ohtsuka, T Tsuruta, Y Ebihara, Y Goto, XY Zhao, K Sakashita, K Koike, M Isomura, S Kojima, A Hoshika, K Tsuji, T Nakahata
BRITISH JOURNAL OF HAEMATOLOGY, 128, 6, 805, 812, BLACKWELL PUBLISHING LTD, 2005年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Aberrant DNA methylation is frequently observed in adults with myelodysplastic syndrome (MDS), and is recognized as a critical event in the disease's pathogenesis and progression. This is the first report to investigate the methylation status of p15 and p16, cell cycle regulatory genes, in children with MDS (n = 9) and juvenile myelomonocytic leukaemia (JMML; n = 18) by using a methylation-specific polymerase chain reaction. The frequency of p15 hypermethylation in paediatric MDS was 78% (7/9), which was comparable to that in adult MDS. In contrast, p15 hypermethylation in JMML was a rare event (17%; 3/18). In JMML, clinical and laboratory characteristics including PTPN11 mutations and aberrant colony formation were not different between the three patients with hypermethylated p15 and the others. Aberrant methylation of p16 was not detected in children with either MDS or JMML. Since p15 and p16 genes were unmethylated in two children with JMML, in whom the disease had progressed with an increased number of blasts, a condition referred to as blastic crisis, we infer that the aberrant methylation of these genes is not responsible for the progression of JMML. The results suggest that demethylating agents may be effective in most children with MDS and a few patients with JMML.

非血縁者間同種骨髄移植後の再発に対するドナーリンパ球輸注(DLI)の臨床検討　　　　　　　　　　　　　　　
河崎 裕英, 長谷川 大輔, 大塚 欣敏, 鶴田 敏久, 真部 淳, 海老原 康博, 辻 浩一郎
日本小児科学会雑誌, 109, 2, 132, 132, (公社)日本小児科学会, 2005年02月
日本語

V-15 Liver hanging maneuver; 切除困難な肝芽腫への適応とその有用性
荒木 夕宇子, 松藤 凡, 堀田 亮, 細谷 亮太, 草川 功, 真部 淳, 青山 千晶, 藤田 真智子
日本小児外科学会雑誌, 41, 3, 416, 416, 特定非営利活動法人 日本小児外科学会, 2005年
日本語

フィラデルフィア染色体陽性急性リンパ性白血病(Ph+ALL)の治療 TCCSG L99-15　　　　　　　　　　　　　　　
真部 淳, 河崎 裕英, 矢部 普正, 小原 明, 高橋 浩之, 生田 孝一郎, 齋藤 友博, 土田 昌宏
小児がん, 41, 3, 558, 558, (NPO)日本小児がん学会, 2004年11月
日本語

非血縁者間同種骨髄移植後の再発に対してドナーリンパ球輸注(DLI)を行った3例　　　　　　　　　　　　　　　
河崎 裕英, 長谷川 大輔, 大塚 欣敏, 海老原 康博, 鶴田 敏久, 真部 淳, 辻 浩一郎
小児がん, 41, 3, 705, 705, (NPO)日本小児がん学会, 2004年11月
日本語

初診ALLにおけるdelayed lumbar puctureの妥当性　　　　　　　　　　　　　　　
康 勝好, 野口 靖, 福島 敬, 富澤 大輔, 太田 節雄, 齋藤 正博, 高橋 裕之, 真部 淳, 小原 明, 生田 孝一郎, 花田 良二, 土田 昌宏, 東京小児がん研究グループ
小児がん, 41, 3, 557, 557, (NPO)日本小児がん学会, 2004年11月
日本語

縦隔原発Desmoplastic small round cell tumorの乳児例　　　　　　　　　　　　　　　
青山 千晶, 伊藤 雄伍, 今村 壽宏, 加藤 格, 神谷 尚宏, 藤田 真智子, 小澤 美和, 森本 克, 真部 淳, 細谷 亮太, 松藤 凡, 鈴木 高祐
小児がん, 41, 3, 631, 631, (NPO)日本小児がん学会, 2004年11月
日本語

急性リンパ性白血病治療中腸重積を機に悪性リンパ腫が発見された5歳男児例　　　　　　　　　　　　　　　
加藤 格, 伊藤 雄伍, 今村 壽宏, 神谷 尚宏, 青山 千晶, 藤田 真智子, 小澤 美和, 森本 克, 真部 淳, 細谷 亮太, 清川 信敬, 藤本 純一郎
小児がん, 41, 3, 727, 727, (NPO)日本小児がん学会, 2004年11月
日本語

Viral infections in juvenile myelomonocytic leukemia: Prevalence and clinical implications
A Manabe, T Yoshimasu, Y Ebihara, H Yagasaki, M Wada, K Ishikawa, J Hara, K Koike, H Moritake, YD Park, K Tsuji, T Nakahata
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 26, 10, 636, 641, LIPPINCOTT WILLIAMS & WILKINS, 2004年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: Viral infections may complicate the diagnosis of juvenile myelomonocytic leukemia (JMML) in a substantial proportion of patients, but this possibility has not been tested in a prospective study. The authors therefore measured the cellular expression of the MxA protein, a reliable marker of viral infection, at diagnosis in children with JMML to estimate the prevalence of such infections.
Methods: Eighteen children, aged 1 to 69 months, who met the diagnostic criteria of the International JMML Working Group were prospectively studied. MxA expression was assessed by flow cytometric analysis of peripheral blood mononuclear cells stained with an antihuman MxA antibody. All data were obtained through the MDS Committee of the Japanese Society of Pediatric Hematology.
Results: Twelve patients (67%) had elevated levels of the MxA protein, with rotavirus, RS virus, or CMV infection documented in three of these patients. Although none of the patients had primary Epstein-Barr virus (EBV) infection, reactivation of the virus was strongly suspected in four children, including two with monosomy 7, each having increased levels of MxA. Southern blot analysis revealed monoclonal integration of the EBV genome into bone marrow mononuclear cells from one of these patients. There was no discernible correlation between increases in the marker protein and the presenting features or course of the disease.
Conclusions: Viral infection may be present in two thirds of children with newly diagnosed JMML, but it does not constitute a basis for revising clinical management. The possibility that EBV or other viruses contribute to JMML pathogenesis by stimulating pre-exiting malignant clones warrants further investigation.

Viral infections in juvenile myelomonocytic leukemia: Prevalence and clinical implications
A Manabe, T Yoshimasu, Y Ebihara, H Yagasaki, M Wada, K Ishikawa, J Hara, K Koike, H Moritake, YD Park, K Tsuji, T Nakahata
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 26, 10, 636, 641, LIPPINCOTT WILLIAMS & WILKINS, 2004年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: Viral infections may complicate the diagnosis of juvenile myelomonocytic leukemia (JMML) in a substantial proportion of patients, but this possibility has not been tested in a prospective study. The authors therefore measured the cellular expression of the MxA protein, a reliable marker of viral infection, at diagnosis in children with JMML to estimate the prevalence of such infections.
Methods: Eighteen children, aged 1 to 69 months, who met the diagnostic criteria of the International JMML Working Group were prospectively studied. MxA expression was assessed by flow cytometric analysis of peripheral blood mononuclear cells stained with an antihuman MxA antibody. All data were obtained through the MDS Committee of the Japanese Society of Pediatric Hematology.
Results: Twelve patients (67%) had elevated levels of the MxA protein, with rotavirus, RS virus, or CMV infection documented in three of these patients. Although none of the patients had primary Epstein-Barr virus (EBV) infection, reactivation of the virus was strongly suspected in four children, including two with monosomy 7, each having increased levels of MxA. Southern blot analysis revealed monoclonal integration of the EBV genome into bone marrow mononuclear cells from one of these patients. There was no discernible correlation between increases in the marker protein and the presenting features or course of the disease.
Conclusions: Viral infection may be present in two thirds of children with newly diagnosed JMML, but it does not constitute a basis for revising clinical management. The possibility that EBV or other viruses contribute to JMML pathogenesis by stimulating pre-exiting malignant clones warrants further investigation.

若年性骨髄単球性白血病(JMML)におけるビスフォスフォネート製剤の検討　　　　　　　　　　　　　　　
大塚 欣敏, 真部 淳, 長谷川 大輔, 河崎 裕英, 辻 浩一郎
日本血液学会・日本臨床血液学会総会プログラム・抄録集, 66回・46回, 951, 951, 日本臨床血液学会, 2004年09月
日本語

有害事象によりL-asparaginase投与を中止した小児急性リンパ性白血病症例の予後　　　　　　　　　　　　　　　
小川 千登世, 生田 孝一郎, 高橋 浩之, 梶原 道子, 前田 美穂, 杉田 憲一, 康 勝好, 菊地 陽, 磯山 恵一, 野口 靖, 矢部 普正, 豊田 恭徳, 真部 淳, 小原 明, 花田 良二, 土田 昌宏, 東京小児がん研究グループALL委員会
日本血液学会・日本臨床血液学会総会プログラム・抄録集, 66回・46回, 751, 751, 日本臨床血液学会, 2004年09月
日本語

小児の低2倍体急性リンパ性白血病(ALL)68例の検討　　　　　　　　　　　　　　　
福島 敬, 康 勝好, 高橋 浩之, 真部 淳, 小原 明, 竹 泰秀, 外松 学, 金子 隆, 上條 岳彦, 磯山 恵一, 木下 明俊, 後藤 裕明, 豊田 恭徳, 前田 美穂, 嶋田 博之, 杉田 憲一, 齋藤 正博, 杉田 完爾, 梶原 道子, 矢部 晋正, 菊地 陽, 中舘 尚也, 野口 靖, 牧本 敦, 柳沢 隆昭, 生田 孝一郎, 花田 良二, 土田 昌宏, 東京小児がん研究グループ
日本血液学会・日本臨床血液学会総会プログラム・抄録集, 66回・46回, 752, 752, 日本臨床血液学会, 2004年09月
日本語

フィラデルフィア染色体陽性急性リンパ性白血病(Ph+ALL)の治療 TCCSG L99-15　　　　　　　　　　　　　　　
真部 淳, 河崎 裕英, 矢部 普正, 小原 明, 高橋 浩之, 生田 孝一郎, 齋藤 友博, 土田 昌宏
日本小児血液学会雑誌, 18, 4, 301, 301, 日本小児血液学会, 2004年08月
日本語

非血縁者間同種骨髄移植後の再発に対してドナーリンパ球輸注(DLI)を行った3例　　　　　　　　　　　　　　　
河崎 裕英, 長谷川 大輔, 大塚 欣敏, 海老原 康博, 鶴田 敏久, 真部 淳, 辻 浩一郎
日本小児血液学会雑誌, 18, 4, 444, 444, 日本小児血液学会, 2004年08月
日本語

初診ALLにおけるdelayed lumbar puctureの妥当性　　　　　　　　　　　　　　　
康 勝好, 野口 靖, 福島 敬, 富澤 大輔, 太田 節雄, 齋藤 正博, 高橋 裕之, 真部 淳, 小原 明, 生田 孝一郎, 花田 良二, 土田 昌宏, 東京小児がん研究グループ
日本小児血液学会雑誌, 18, 4, 300, 300, 日本小児血液学会, 2004年08月
日本語

縦隔原発Desmoplastic small round cell tumorの乳児例　　　　　　　　　　　　　　　
青山 千晶, 伊藤 雄伍, 今村 壽宏, 加藤 格, 神谷 尚宏, 藤田 真智子, 小澤 美和, 森本 克, 真部 淳, 細谷 亮太, 松藤 凡
日本小児血液学会雑誌, 18, 4, 370, 370, 日本小児血液学会, 2004年08月
日本語

急性リンパ性白血病治療中腸重積を機に悪性リンパ腫が発見された5歳男児例　　　　　　　　　　　　　　　
加藤 格, 伊藤 雄伍, 今村 壽宏, 神谷 尚宏, 青山 千晶, 藤田 真智子, 小澤 美和, 森本 克, 真部 淳, 細谷 亮太, 清川 信敬
日本小児血液学会雑誌, 18, 4, 466, 466, 日本小児血液学会, 2004年08月
日本語

神経芽腫に対する遺伝子治療(第I相臨床試験)の問題点　　　　　　　　　　　　　　　
大塚 欣敏, 長谷川 大輔, 鶴田 敏久, 河崎 裕英, 海老原 康博, 広瀬 偉美子, 真部 淳, 辻 浩一郎, 黒田 達夫, 佐藤 雄也, 谷澤 昭彦, 山下 直秀
小児がん, 40, 3, 448, 448, (NPO)日本小児がん学会, 2003年11月
日本語

小児骨髄異形成症候群 (myelodysplastic syndrome : MDS) : 最近の話題
真部 淳
日本小児血液学会雑誌, 17, 5, 429, 432, THE JAPANESE SOCIETY OF PEDIATRIC HEMATOLOGY/ONCOLOGY, 2003年10月30日
日本語

AMLI/RUNXI mutations are infrequent, but related to AML-M0, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies
T Taketani, T Taki, J Takita, M Tsuchida, R Hanada, T Hongo, T Kaneko, A Manabe, K Ida, Y Hayashi
GENES CHROMOSOMES & CANCER, 38, 1, 1, 7, WILEY-BLACKWELL, 2003年09月, ［査読有り］
英語, 研究論文（学術雑誌）, AML1/RUNX1, located on chromosome band 21 q22, is one of the most important hematopoietic transcription factors. AML1 is frequently affected in leukemia and myelodysplastic syndrome with 21 q22 translocations. Recently, AML1 mutations were found in adult hematologic malignancies, especially acute myeloid leukemia (AML)-M0 or leukemia with acquired trisomy 21, and familial platelet disorder with a predisposition toward AML. Through the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we examined the AML1 gene for mutations in 241 patients with pediatric hematologic malignancies, and we detected AML1 mutations in seven patients (2.9%). Deletion was found in one patient, and point mutations in four patients, including three missense mutations, two silent mutations, and one mutation within an intron resulting in an abnormal splice acceptor site. All of the mutations except for one were heterozygous. Mutations within the runt domain were found in six of seven patients. Six of seven patients with AML1 mutations were diagnosed with AML, and one had acute lymphoblastic leukemia. In three of these seven patients, AML evolved from other hematologic disorders. AML1 mutations were found in two of four AML-M0 and two of three patients with acquired trisomy 21. Patients with AML1 mutations tended to be older children. Three of four patients with AML1 mutations who received stem cell transplantation (SCT) are alive, whereas the remaining three patients with mutations without SCT died. These results suggest that AML1 mutations in pediatric hematologic malignancies are infrequent, but are possibly related to All acquired trisomy 2 1, and leukemic transformation. These patients may have a poor clinical outcome. (C) 2003 Wiley-Liss, Inc.

ALLに対するVP-16を含まないレジメンによる化学療法後に発症したtopoisomerase II阻害剤関連性急性骨髄性白血病　　　　　　　　　　　　　　　
長谷川 大輔, 真部 淳, 大塚 欣敏, 鶴田 敏久, 河崎 裕英, 海老原 康博, 辻 浩一郎, 前田 美穂
臨床血液, 44, 9, 975, 975, (一社)日本血液学会-東京事務局, 2003年09月
日本語

CD7/CD13陽性急性白血病の1例　　　　　　　　　　　　　　　
長谷川 大輔, 真部 淳, 鶴田 敏久, 大塚 欣敏, 海老原 康博, 河崎 裕英, 有瀧 健太郎, 松浦 恵子, 辻 浩一郎
日本小児血液学会雑誌, 17, 4, 263, 263, 日本小児血液学会, 2003年08月
日本語

DIC,高カルシウム血症を合併した(17;19)番転座を伴った急性リンパ性白血病の1例　　　　　　　　　　　　　　　
大塚 欣敏, 長谷川 大輔, 鶴田 敏久, 河崎 裕英, 海老原 康博, 真部 淳, 杉田 記代子, 田中 葉子, 稲葉 俊哉, 本郷 輝明, 辻 浩一郎
日本小児血液学会雑誌, 17, 4, 283, 283, 日本小児血液学会, 2003年08月
日本語

Successful treatment of natural killer (NK) cell leukemia following a long-standing chronic active Epstein-Barr virus (CAEBV) infection with allogeneic bone marrow transplantation
Y Ebihara, A Manabe, R Tanaka, T Yoshimasu, K Ishikawa, T Iseki, J Hayakawa, M Maeda, S Asano, K Tsuji
BONE MARROW TRANSPLANTATION, 31, 12, 1169, 1171, NATURE PUBLISHING GROUP, 2003年06月, ［査読有り］
英語, 研究論文（学術雑誌）, The optimal treatment for natural killer (NK) cell leukemia after chronic active Epstein-Barr virus (CAEBV) infection has not been determined. A 15-year-old boy presented with NK cell leukemia following CAEBV infection for 5 years. The peripheral blood and BM had an increased number of CD3(-)CD56(+) large granular lymphocytes and a monoclonal integration of the EBV genome was detected. Chemotherapy was not sufficiently effective to control the disease. Allogeneic BMT from an HLA-identical sister was performed using a conditioning regimen consisting of total body irradiation, cyclophosphamide and thiotepa. The patient is disease-free with a perfect performance status 24 months after BMT. This is the first report to show that allogeneic BMT is potentially able to cure NK cell leukemia after CAEBV infection.

Effects of sodium in hydration solution on plasma methotrexate concentrations following high-dose methotrexate in children with acute lymphoblastic leukemia
A Kinoshita, Y Kurosawa, K Kondoh, T Suzuki, A Manabe, T Inukai, K Sugita, S Nakazawa
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 51, 3, 256, 260, SPRINGER-VERLAG, 2003年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: To test whether a higher sodium dose in the hydration solution may facilitate faster methotrexate (MTX) elimination as compared with a lower sodium dose following high-dose MTX (HDMTX) treatment. Methods: Intravenous solutions with alternate doses of sodium (regimen A 70 mEq/l, regimen B 100 mEq/l) were given to 30 children with acute lymphoblastic leukemia in two courses of HDMTX in a randomized crossover fashion. The plasma MTX concentrations every 24 h from the beginning of MTX administration and the adverse events associated with HDMTX were compared between the two hydration regimens. Results: The plasma MTX concentrations were similar in the two hydration regimens at 24 h (A 50.9 +/- 7.4 vs B 40.9 +/- 5.4 muM, means +/- SE, P = 0.17), but was significantly lower in regimen B at 48 and 72 h (A 0.65 +/- 0.17 vs B 0.27 +/- 0.03 muM, P=0.04; and A 0.14 +/- 0.03 vs B 0.05 +/- 0.01 muM, P=0.003). The time during which MTX plasma concentrations exceeded 0.1 muM was significantly longer in regimen A than in regimen B (A 3.83 +/- 0.18 vs B 3.13 +/- 0.06 days, P = 0.001). The incidences of adverse events were similar between the two regimens (P=0.78), and severe adverse events were not seen in either regimen. Conclusions: Hydration with a higher sodium dose facilitated faster MTX elimination following HDMTX. Sodium may have a beneficial effect on MTX-induced nephrotoxicity.

Third International Symposium on Myelodysplastic Syndromes in Childhood
Atsushi Manabe, Yoshitoshi Ohtsuka
International Journal of Hematology, 78, 5, 475, 476, Springer Tokyo, 2003年, ［査読有り］
英語, 研究論文（国際会議プロシーディングス）, This article summarizes presentations from the Third International Symposium on Myelodysplastic Syndromes in Childhood, April 27-29, 2003, in Stresa, Italy. Topics included epidemiology, pathology, cytogenetics, molecular biology, pathophysiology, and treatment. Dr. Susanna Fenu was the Meeting Chair. ©2003 The Japanese Society of Hematology.

Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34(+) CD38(-) cells expressing Flk2/Flt3
Y Ebihara, M Wada, T Ueda, MJ Xu, A Manabe, R Tanaka, M Ito, H Mugishima, S Asano, T Nakahata, K Tsuji
BRITISH JOURNAL OF HAEMATOLOGY, 119, 2, 525, 534, BLACKWELL PUBLISHING LTD, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）, In the present study, we examined the expression of Flk2/Flt3, a tyrosine kinase receptor, on human cord blood CD34(+) haematopoietic progenitor/stem cells. In flow cytometric analysis, Flk2/Flt3 was expressed on 80% of CD34(+) cells and their immature subpopulations, CD34(+) CD33(-) and CD34(+) CD38(-) cells. Methycellulose clonal culture of sorted CD34(+) Flk2/ Flt3(+) and CD34(+) Flk2/Flt3(-) cells showed that most of myelocytic progenitors expressed Flk2/Flt3, but erythroid and haematopoietic multipotential progenitors were shared by both fractions. When 1 x 10(4) lineage marker-negative (Lin(-))CD34(+)Flk2/Flt3(-) cells were transplanted into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, none of the recipients possessed human CD45(+) cells in bone marrow 11-12 weeks after the transplantation. In contrast, all recipients transplanted with 1 x 10(4) Lin(-) CD34(+) Flk2/Flt3(+) cells showed successful engraftment. Furthermore, clonal cells expanded from single Lin(-) CD34(+) CD38(-) Flk2/Flt3(+) cells in the culture with Flk2/Flt3 ligand, stem cell factor, thrombopoietin, and a complex of interleukin 6/soluble interleukin 6 receptor were individually transplanted into NOD/SCID mice. At 20 to 21 weeks after the transplantation, three out of 10 clones harvested at d 7 of culture, and three out of six clones at d 14 could reconstitute human haematopoiesis in recipient marrow. These results demonstrated that Flk2/Flt3 was expressed on a wide variety of human haematopoietic cells including long-term-repopulating haematopoietic stem cells.

短期決戦型TCCSG ALL L92-13再発例の救済とQOLについて　　　　　　　　　　　　　　　
杉田 憲一, 土田 昌宏, 生田 孝一郎, 花田 良二, 金子 隆, 小池 和俊, 角南 勝介, 矢部 みはる, 菊地 陽, 木下 俊明, 渋谷 温, 藤田 宏夫, 高山 順, 外松 学, 加藤 陽子, 森本 克, 沖本 由理, 豊田 恭徳, 小森 功夫, 前田 美穂, 真部 淳, 斉藤 友博, 中澤 眞平, 東京小児がん研究グループ
臨床血液, 43, 8, 327, 327, (一社)日本血液学会-東京事務局, 2002年08月
日本語

溶血性貧血,血小板減少にて発症したALPSの一例　　　　　　　　　　　　　　　
稲井 郁子, 森本 克, 小澤 美和, 真部 淳, 金兼 弘和, 宮脇 利男, 三輪 操子, 細谷 亮太
日本小児血液学会雑誌, 16, 4, 267, 267, 日本小児血液学会, 2002年08月
日本語

Successful treatment of relapsed blastic natural killer cell lymphoma with unrelated cord blood transplantation
T Yoshimasu, A Manabe, R Tanaka, S Mochizuki, Y Ebihara, K Ishikawa, T Iseki, N Oyaizu, K Aritaki, K Tanaka, T Tsuruta, A Hoshika, S Asano, K Tsuji
BONE MARROW TRANSPLANTATION, 30, 1, 41, 44, NATURE PUBLISHING GROUP, 2002年07月, ［査読有り］
英語, 研究論文（学術雑誌）, The prognosis for blastic natural killer (NK) cell lymphoma is generally dismal. We report a patient who was successfully treated with unrelated cord blood transplantation (UCBT). A 15-year-old boy was diagnosed as having blastic NK cell lymphoma in the cervical lymph nodes. Autologous peripheral blood stem cell transplantation was performed on achieving a complete remission. However, the disease recurred in the bone marrow 6 months later. Chemotherapy induced a second remission and the patient received UCBT with a conditioning regimen consisting of total body irradiation, thiotepa and cyclophosphamide. Chronic GVHD of the lung occurred, but it was well controlled with steroids. At the time of writing, he remains in remission 18 months after UCBT with an excellent performance status. UCBT may be an option for patients with blastic NK cell lymphoma.

Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region-derived stromal cells
S Matsuoka, K Tsuji, H Hisakawa, MJ Xu, Y Ebihara, T Ishii, D Sugiyama, A Manabe, R Tanaka, Y Ikeda, S Asano, T Nakahata
BLOOD, 98, 1, 6, 12, AMER SOC HEMATOLOGY, 2001年07月, ［査読有り］
英語, 研究論文（学術雑誌）, There is controversy as to whether murine definitive hematopoiesis originates from yolk sac (YS) or the intraembryonic region. This study reports the generation of definitive hematopoietic stem cells (HSCs) from both early YS and infraembryonic paraaortic splanchnopleures (P-Sp) on AGM-S3 stromal cells derived from:the aorta-gonad-mesonephros (AGM) region at 10.5 days post coitum (dpc). YS and P-Sp cells at 8.5 dpc generated no definitive hematopoiesis-derived colony-forming cells in: cocultures with AGM-S3 cells, but spleen colony-forming cells and HSCs capable of reconstituting definitive hematopoiesis In adult mice simultaneously appeared on day 4 of coculture. Precursors for definitive HSCs were present in YS and P-Sp at 8.0 dpc, a time when YS and embryo were not connected by blood vessels. It is proposed that precursors with the potential to generate definitive HSCs appear independently in YS and intraembryonic P-Sp and that the P-Sp or AGM region affords the microenvironment that facilitates generation of definitive hematopoiesis from precursors. (C) 2001 by The American Society of Hematology.

Surfactant protein D and KL-6 as serologic indicators of Pneumocystis carinii pneumonia in a child with acute lymphoblastic leukemia
Takashi Takahashi, Yasuhiro Ebihara, Atsushi Manabe, Kohichiro Tsuji, Tetsuya Nakamura, Tatsutoshi Nakahata, Aikichi Iwamoto
Journal of Medicine, 32, 1-2, 41, 51, 2001年, ［査読有り］
英語, 研究論文（学術雑誌）, Pneumocystis carinii pneumonia (PCP) in immunocompromised patients is one of the important causes of morbidity and mortality. Serum levels of surfactant protein D (SP-D) and KL-6 are useful biomarkers for understanding some pulmonary inflammatory responses in patients with idiopathic pulmonary fibrosis (IPF). We present a child with PCP following bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL), for whom both SP-D and KL-6 in sera were simultaneously measured through the clinical course of PCP. Both serum levels of SP-D and KL-6 were rapidly elevated reflecting some inflammatory processes in the lung that chest X-ray films and CT scans showed as ground-glass attenuations. He died due to respiratory failure 40 days after PCP developed. A combination of the assays for SP-D and KL-6 in sera may be helpful in predicting the treatment results for PCP.

C67 進行神経芽腫に対する樹状細胞を用いた免疫療法の基礎的研究
中原 さおり, 真部 淳, 浅野 茂隆, 辻 浩一郎, 橋都 浩平
日本小児外科学会雑誌, 36, 3, 250, 250, 特定非営利活動法人 日本小児外科学会, 2000年
日本語

Second international symposium on myelodysplastic syndromes in childhood
Atsushi Manabe
International Journal of Hematology, 72, 4, 522, 524, 2000年, ［査読有り］
英語, 研究論文（学術雑誌）, This article summarizes presentations from the Second International Symposium on Myelodysplastic Syndromes in Childhood, May 11 to 14,2000, in Funen, Denmark. Topics included epidemiology, pathology, pathophysiology, cytogenetics, congenital neutropenia, transplantation, and classification. Dr. Henrik Hasle was the Meeting Chair and Dr. Gitte Kerndrup was the Co-Chair. © 2000 The Japanese Society of Hematology.

ヒト臍帯血CD34陽性細胞におけるFlk2/Flt3の発現　　　　　　　　　　　　　　　
海老原 康博, 植田 高弘, 吉野 浩, 石井 武文, 谷ヶ崎 博, 久川 浩章, 三井 哲夫, 郡司 勇治, 田中 竜平, 真部 淳
臨床血液, 40, 9, 921, 921, (一社)日本血液学会-東京事務局, 1999年09月
日本語

治療後期のL-アスパラギナーゼにより重症膵炎を発症したALLの1女児例　　　　　　　　　　　　　　　
石井 武文, 真部 淳, 海老原 康博, 植田 高弘, 吉野 浩, 三井 哲夫, 久川 浩章, 谷ヶ崎 博, 菊地 陽, 辻 浩一郎
日本小児血液学会雑誌, 13, 4, 261, 261, 日本小児血液学会, 1999年08月
日本語

再生不良性貧血と骨髄異形成症候群の境界例と考えられた1例　　　　　　　　　　　　　　　
吉野 浩, 植田 高弘, 真部 淳, 菊地 陽, 海老原 康博, 三井 哲夫, 久川 浩章, 石井 武文, 谷ヶ崎 博, 辻 浩一郎
日本小児血液学会雑誌, 13, 4, 320, 320, 日本小児血液学会, 1999年08月
日本語

再発急性骨髄性白血病患児にみられたNeutropenic enterocolitis(Typhlitis)の1例　　　　　　　　　　　　　　　
吉野 浩, 真部 淳, 海老原 康博, 植田 高弘, 石井 武文, 江口 直宏, 三井 哲夫, 久川 浩章, 谷ヶ崎 博, 菊地 陽
日本小児科学会雑誌, 103, 4, 478, 479, (公社)日本小児科学会, 1999年04月
日本語

Fifth international symposium on myelodysplastic syndromes
Atsushi Manabe
International Journal of Hematology, 70, 4, 296, 300, 1999年, ［査読有り］
英語, 研究論文（学術雑誌）

ステロイドが奏効した同種骨髄移植後Bronchiolitis Obliterans Organizing Pneumonia(BOOP)の一例　　　　　　　　　　　　　　　
石井 武文, 真部 淳, 海老原 康博, 植田 高弘, 吉野 浩, 江口 直宏, 三井 哲夫, 久川 浩章, 谷ヶ崎 博, 菊地 陽
日本小児血液学会雑誌, 12, 4, 221, 221, 日本小児血液学会, 1998年08月
日本語

Hydroxyureaで芽球のコントロールを行い,非血縁者間骨髄移植(uBMT)を施行した再発急性骨髄性白血病の一例　　　　　　　　　　　　　　　
吉野 浩, 真部 淳, 海老原 康博, 植田 高弘, 石井 武文, 江口 直宏, 三井 哲夫, 久川 浩章, 谷ヶ崎 博, 菊地 陽
日本小児血液学会雑誌, 12, 4, 231, 231, 日本小児血液学会, 1998年08月
日本語

Ph1 ALL症例の造血幹細胞移植における多分割高線量の全身照射(TBI)の試み　　　　　　　　　　　　　　　
菊地 陽, 海老原 康博, 植田 高弘, 吉野 浩, 石井 武文, 江口 直宏, 三井 哲夫, 久川 浩章, 谷ヶ崎 博, 真部 淳
日本小児血液学会雑誌, 12, 4, 227, 227, 日本小児血液学会, 1998年08月
日本語

G-CSF投与中に脳梗塞をきたしたT-ALLの1例
小澤 美和, 真部 淳, 海老原 康博
日本小児血液学会雑誌, 11, 6, 436, 440, 日本小児血液学会, 1997年12月
日本語, 14歳女児,寛解導入療法中,白血球数が300/μlと減少し,第5週よりG-CSFの投与を開始後,15日目に白血球数が39,300/μlと急激に上昇した時点で投与を中止した.同日,Jacksonian typeの間代性けいれんを認めた.4日目の頭部CT,8日目のMRI所見で梗塞が疑われ,12日目の脳血流シンチグラムでも一過性の血流低下を示した.約5週後のhigh dose AraC(3g/m2)終了後,再度G-CSFの投与を3日間行い白血球数が300/μlから2,800/μlとなったところで頭部CTと血流シンチグラムを行ったところ,再び虚血性変化を認めた.G-CSFにより正常顆粒球が急激に増加したことが血液の粘稠度を上昇させたと考えられた

溶連菌感染症とアレルギー性紫斑病との関連について 最近10年間におけるアレルギー性紫斑病についての検討
折居建治, 大矢達男, 大山栄作, 平田倫生, 斎藤昭彦, 海老原康博, 渡部玉蘭, 真部淳, 西村昂三
聖路加健康科学誌, 4/5(1994/1995), 30, 34, 1997年07月
日本語

^<67>Gaシンチグラフィーにおいて肝への集積の消失と骨への著しい集積を認めた急性リンパ性白血病の1例
折居 建治, 真部 淳, 平田 倫生, 海老原 康博, 渡部 玉蘭, 西村 昂三, 細谷 亮太
日本小児血液学会雑誌, 11, 2, 120, 124, 日本小児血液学会, 1997年04月30日
日本語, 5歳女児.急性リンパ性白血病の発症初期に67Gaシンチグラフィーを施行され,骨への異常集積を認めた.その機序としては白血病細胞に67Ga-citrateが取り込まれ,そのために骨髄への集積をきたしたと考えられた.本例では治療に伴う画像所見の正常化が認められ,67Gaシンチグラフィーが発症初期の白血病細胞量の変化を推察する上で有用な補助検査法になり得ることを示唆している

Human B-cell progenitors and bone marrow microenvironment.　　　　　　　　　　　　　　　
Campana D, Coustan-Smith E, Manabe A, Kumagai M, Murti KG, Silvennoinen O, Nishigaki H, Kitanaka A, Ito C
Human cell, 9, 4, 317, 322, 1996年12月, ［査読有り］

52. 先天性神経芽腫 (NB) stage III の1例(第30回日本小児外科学会関東甲信越地方会)
加地 展之, 松藤 凡, 真部 淳, 細谷 亮太, 横山 穣太郎
日本小児外科学会雑誌, 32, 7, 1161, 1161, 特定非営利活動法人 日本小児外科学会, 1996年
日本語

26 神経芽腫の年齢とステージ別の治療方法と成績(乳児例(非MS)、進行例の手術はどうあるべきか, V.神経芽腫, 第11回日本小児外科学会秋季シンポジウム)
松藤 凡, 細谷 亮太, 真部 淳, 横山 穣太郎
日本小児外科学会雑誌, 31, 6, 871, 871, 特定非営利活動法人 日本小児外科学会, 1995年
日本語

63. 多発皮下転移を認めた小円形細胞肉腫の1例(第29回関東甲信越地方会)
澤村 聡美, 松藤 凡, 細谷 亮太, 真部 淳, 植草 利公, 横山 譲太郎, 秦 順一
日本小児外科学会雑誌, 31, 1, 127, 127, 特定非営利活動法人 日本小児外科学会, 1995年
日本語

心房性ナトリウム利尿ペプチド(ANP)のラット肝組織血流量におよぼす影響
真部 淳
杏林医学会雑誌, 21, 4, 477, 486, 杏林医学会, 1990年
日本語, 心房性ナトリウム利尿ペプチド(ANP)の肝組織血流量におよぼす影響について,正常ラットおよび四塩化炭素肝硬変ラットにANPを投与して,肝組織血流量,血圧の変化を検討した。正常ラットでは,肝組織血流量はANP10, 100および1000μg/kgのいずれの用量においても投与1分後,10分後および20分後の測定で有意な変動を認めなかった。また,平均血圧は10μg/kg,100μg/kgでは変動を認めず,1000μg/kgでは投与1分後に9mmHgの有意(p<0.05)の低下を認めた。肝硬変ラットでは,肝組織血流量はANP10μg/kgで変化せず,100μg/kgでは投与1分後に20%の有意(P<0.05)の増加を,1000μg/kgでは投与1分後には反対に17%の減少を認めた。平均血圧は10μg/kgで変化せず,100μg/kgでは投与1分後に12mmHg,1000μg/kgでは投与1分後に17mmHgと,それぞれ有意(P<0.05, P<0.05)の低下を認めた。ANPは肝硬変ラットの肝組織血流量に対し用量によって異なる反応を示したが,正常ラットでは有意な変化は見られなかった。血圧は正常ラットおよび肝硬変ラットともに用量依存性に低下したが,その程度は肝硬変ラットで,より大であった。以上より,ANPに対する反応性が肝硬変ラットでは正常ラットと異なることが明らかにされた。

I-E-41 小児急性リンパ性白血症同胞発生のみられた2家族における両親の心理的反応(腫瘍・死の臨床)(一般口演)
細谷 亮太, 真部 淳, 岩堀 晃, 西村 昂三
心身医学, 28, 108, 108, 一般社団法人 日本心身医学会, 1988年
日本語

AFP上昇を伴う未熟奇形腫の治療
山口秀, 伊師雪友, 大木聡悟, 茂木洋晃, 長谷河昌孝, 寺下友佳代, 平林真介, 西岡健太郎, 橋本孝之, 真部淳, 藤村幹, 小児の脳神経(Web), 49, 2, 2024年

当院の原発性脳腫瘍患者におけるがん遺伝子パネル検査の実情
山口秀, 茂木洋晃, 澤谷亮佑, 伊師雪友, 寺下友佳代, 平林真介, 杉山未奈子, 齋藤祐介, 木下一郎, 真部淳, 藤村幹, 日本脳腫瘍学会学術集会プログラム・抄録集, 41st, 2023年

IMMUNOPHENOTYPIC AND CHROMOSOMAL CHARACTERIZATION OF KMT2A GERMLINE ACUTE LYMPHOBLASTIC LEUKEMIA IN INFANTS
Hiroki Yoshihara, Takako Miyamura, Takao Deguchi, Toshinori Hori, Tomohiko Taki, Kunihiko Moriya, Yuki Arakawa, Mariko Eguchi, Kunihiro Shinoda, Yuhki Koga, Katsuyoshi Koh, Atsushi Manabe, Keizo Horibe, Daisuke Tomizawa, PEDIATRIC BLOOD & CANCER, 69, 2022年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

乳児へのボリコナゾール投与中に、代謝機能の発達によると考えられる著しい血中濃度低下が認められた1例
山口 敦史, 田澤 佑基, 武隈 洋, 植木 将弘, 山田 雅文, 真部 淳, 菅原 満, TDM研究, 39, 2, 136, 136, 2022年05月
(一社)日本TDM学会, 日本語

早産出生の乳幼児の睡眠と精神発達　　　　　　　　　　　　　　　
太田 英伸, 安藤 明子, 吉村 優子, 中川 真智子, 安積 陽子, 中澤 貴代, 三谷 裕介, 大石 芳久, 水島 正人, 安達 裕行, 兼次 洋介, 森岡 圭太, 島袋 林秀, 平田 倫生, 池田 尊司, 福冨 理佳, 小林 京子, 小澤 美和, 竹島 正浩, 真部 淳, 高橋 勉, 三島 和夫, 草川 功, 與田 仁志, 菊知 充, 長 和俊, 精神神経学雑誌, 124, 4付録, S, 517, 2022年04月
(公社)日本精神神経学会, 日本語

多発性脳内出血で発症し急激な経過で脳死に至ったT細胞性急性リンパ性白血病(T-ALL)
長祐子, 澤井彩織, 原和也, 寺下友佳代, 杉山未奈子, 平林真介, 真部淳, 杉山拓, 方波見謙一, 浜崎和朗, 日本小児科学会雑誌, 126, 2, 2022年

Chemotherapy with the Use of TKIs Based on MRD Has the Potential to Avoid Hematopoietic Stem Cell Transplantation in Treatment for Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph plus ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study ALL-Ph13
Atsushi Sato, Hirohide Kawasaki, Takao Deguchi, Yoshiko Hashii, Yuka Iijima-Yamashita, Sachiko Yonezawa, Chiyo K. Imamura, Haruko Shima, Hirotoshi Sakaguchi, Yuichi Kodama, Keisuke Kato, Motohiro Kato, Hidefumi Hiramatsu, Nobutaka Kiyokawa, Akiko Kada, Akiko M. Saito, Keizo Horibe, Atsushi Manabe, Hiroyuki Shimada, BLOOD, 138, 2021年11月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

新規の白血病特性を有するmyeloid/natural killer cell precursor acute leukemia(Myeloid/natural killer(NK) cell precursor acute leukemia as a novel distinctive leukemia entity)　　　　　　　　　　　　　　　
西村 聡, 横山 和明, 成戸 卓也, 中園 博仁, 木村 俊介, 今村 俊彦, 森尾 友宏, 金井 昭教, 松井 啓隆, 梅田 雄嗣, 佐野 秀樹, 小池 隆志, 頼 晋也, 關中 悠仁, 小川 淳, 木下 明俊, 柴 徳生, 三木 瑞香, 木村 文彦, 中山 秀樹, 中沢 洋三, 多賀 崇, 滝 智彦, 足立 壯一, 真部 淳, 康 勝好, 石田 也寸志, 滝田 順子, 東條 有伸, 高木 正稔, 日本血液学会学術集会, 83回, PL, 4, 2021年09月
(一社)日本血液学会, 英語

Comprehensive Genetic Analysis Revealed Myeloid/Natural Killer (NK) Cell Precursor Acute Leukemia As a Novel Distinctive Leukemia Entity
Akira Nishimura, Kazuaki Yokoyama, Chika Yamagishi, Toshihiko Imamura, Takuya Naruto, Tomohiro Morio, Yukie Tanaka, Akinori Kanai, Hirotaka Matsui, Naoko Higuchi, Akiko Takada, Haruna Okuno, Shoji Saito, Shuhei Karakawa, Shogo Kobayashi, Daisuke Hasegawa, Hiroyuki Fujisaki, Daiichiro Hasegawa, Kazutoshi Koike, Takashi Koike, Shinya Rai, Katsutsugu Umeda, Hideki Sano, Yujin Sekinaka, Atsushi Ogawa, Akitoshi Kinoshita, Norio Shiba, Mizuka Miki, Fumihiko Kimura, Hideki Nakayama, Yozo Nakazawa, Takashi Taga, Tomohiko Taki, Souichi Adachi, Atsushi Manabe, Katsuyoshi Koh, Yasushi Ishida, Arinobu Tojo, Masatoshi Takagi, BLOOD, 136, 2020年11月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

小児血液・腫瘍性疾患の治療中にPRESによる非けいれん性てんかん重積を認めた2例　　　　　　　　　　　　　　　
山本 薫, 代田 惇朗, 長谷川 大輔, 木村 俊介, 吉本 優里, 平林 真介, 細谷 要介, 野崎 太希, 横山 美奈, 真部 淳, 荻原 正明, 日本小児科学会雑誌, 124, 9, 1391, 1396, 2020年09月
症例1(4歳女児)。急性リンパ性白血病に対する寛解導入療法開始31日に意識障害、右下肢間代発作を認めた。その後も意識障害が持続し、3日後の脳波検査およびMRI検査にて可逆性後部白質脳症(PRES)による非けいれん性てんかん重積状態(NCSE)と診断された。クロバザム(CLB)を投与するもNCSEのコントロールに苦慮し、白血病の治療後も焦点てんかんが後遺症として残った。現在、CLBのの内服を継続し、てんかん発作は消失している。症例2(7歳女児)。全身転移を有する治療抵抗性横紋筋肉腫へのパゾパニブの投与中に左上肢の間代発作が出現し、頭部MRI検査にてPRESと診断された。その後は意識障害が遷延し、脳波検査でNCSEと判明、抗てんかん薬を投与したところ、NCSEは消失し、意識状態の改善が得られた。, (公社)日本小児科学会, 日本語

NUDT15 Variants Confer High Incidence of Secondary Malignancies of ALL in Children
Masanori Yoshida, Kazuhiko Nakabayashi, Aiko Sato-Otsubo, Shinichi Tsujimoto, Kaoru Yoshida, Ryota Shirai, Tomoo Osumi, Yuki Yuza, Masatoshi Takagi, Hiroyuki Takahashi, Katsuyoshi Koh, Akitoshi Kinoshita, Moeko Hino, Toshihiko Imamura, Yozo Nakazawa, Okuya Mayuko, Harumi Kakuda, Masashi Sanada, Kimikazu Matsumoto, Daisuke Tomizawa, Nobutaka Kiyokawa, Akira Ohara, Atsushi Manabe, Kenichiro Hata, Jun J. Yang, Motohiro Kato, BLOOD, 134, 2019年11月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

多彩な自己炎症性疾患を紐解く Linear ubiquitin assembly complexとOTULINによる炎症と細胞死の制御 OTULIN-related autoinflammatory syndrome患者の解析を通して　　　　　　　　　　　　　　　
植木 将弘, 松廣 淳平, 竹崎 俊一郎, 藤田 宏明, 三宅 紀子, 戸澤 雄介, 山田 雅文, 小林 一郎, 松本 直通, 有賀 正, 岩井 一宏, 真部 淳, 日本小児リウマチ学会総会・学術集会プログラム・抄録集, 29回, 52, 52, 2019年10月
(一社)日本小児リウマチ学会, 日本語

大頭症、軽度運動発達遅滞、白質信号異常を呈し、PTEN遺伝子変異を認めた男児例　　　　　　　　　　　　　　　
黒子 由梨香, 山本 薫, 横山 美奈, 代田 惇朗, 平林 真介, 真部 淳, 荻原 正明, 草川 功, 青木 洋子, 小崎 里華, 脳と発達, 51, Suppl., S359, S359, 2019年05月
(一社)日本小児神経学会, 日本語

造血細胞移植後に生じた腸管気腫症に対して間欠的酸素投与が有効であった3例
足洗美穂, 西村聡, 西村聡, 神谷尚宏, 山本俊亮, 小野林太郎, 友田昴宏, 山本薫, 井上健斗, 井上真依子, 廣木遥, 宮本智史, 星野顕宏, 梅原直, 平林真介, 岡本健太郎, 柳町昌克, 磯田健志, 細谷要介, 長谷川大輔, 今井耕輔, 高木正稔, 金兼弘和, 森尾智宏, 真部淳, 日本造血細胞移植学会総会プログラム・抄録集, 41st, 2019年

症例 発汗過多,成長障害を契機に診断に至った神経芽腫の一例
橋本 佳帆子, 中山 加奈子, 山口 健史, 原 和也, 寺下 友佳代, 杉山 未奈子, 長 祐子, 井口 晶裕, 本多 昌平, 中村 明枝, 真部 淳, 臨床小児医学 = The Journal of clinical pediatrics, Sapporo, 67, 1, 84, 89, 2019年
日本小児科学会北海道地方会, 日本語

Characteristics and Treatment Outcome of Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia not Enrolled on Clinical Trials in TKI-era
Keisuke Kato, Hirotoshi Sakaguchi, Yuichi Kodama, Yuichi Shinkoda, Akira Shimada, Takashi Iwase, Junko Takita, Chitose Ogawa, Hidefumi Hiramatsu, Motohiro Kato, Atsushi Sato, Hideko Uryu, Tsuyako Iwai, Akiko Saito, Hirohide Kawasaki, Katsuyoshi Koh, Atsushi Manabe, Keizo Horibe, Hiroyuki Shimada, PEDIATRIC BLOOD & CANCER, 65, S64, S65, 2018年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Clinical Feature and Genetic Alterations in Myeloid/Natural Killer (NK) Cell Precursor Acute Leukemia and Myeloid/NK Cell Acute Leukemia
Akira Nishimura, Kazuaki Yokoyama, Chika Yamagishi, Takuya Naruto, Tomohiro Morio, Akinori Kanai, Hirotaka Matsui, Naoko Higuchi, Akiko Takada, Haruna Okuno, Shoji Saito, Shuhei Karakawa, Shogo Kobayashi, Hideki Sano, Takashi Koike, Daisuke Hasegawa, Hiroyuki Fujisaki, Daiichiro Hasegawa, Kazutoshi Koike, Atsushi Ogawa, Akitoshi Kinoshita, Norio Shiba, Mizuka Miki, Hideki Nakayama, Yozo Nakazawa, Toshihiko Imamura, Takashi Taga, Souichi Adachi, Katsuyoshi Koh, Atsushi Manabe, Tomohiko Taki, Yasushi Ishida, Arinobu Tojo, Masatoshi Takagi, BLOOD, 132, 2018年11月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

DNA Methylation-Based Characterization of T-cell Acute Lymphoblastic Leukemia Well Correlated with Genetic Features, Prognosis and Differentiation Stages
Shunsuke Kimura, Masafumi Seki, Tomoko Kawai, Kenichi Yoshida, Tomoya Isobe, Hiroo Ueno, Yusuke Shiozawa, Hiromichi Suzuki, Yuichi Shiraishi, Kentaro Ohki, Motohiro Kato, Katsuyoshi Koh, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Atsushi Manabe, Masashi Sanada, Akira Ohara, Keizo Horibe, Masao Kobayashi, Akira Oka, Yasuhide Hayashi, Satoru Miyano, Kenichiro Hata, Seishi Ogawa, Junko Takita, PEDIATRIC BLOOD & CANCER, 65, S21, S22, 2018年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

The Prognostic Value of TP53 Mutations Depends on Clinical Backgrounds in Pediatric Patients with Acute Lymphoblastic Leukemia
Hiroo Ueno, Kenichi Yoshida, Yusuke Shiozawa, Yasuhito Nannya, Yuka Iijima-Yamashita, Nobutaka Kiyokawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Tomoya Isobe, Masafumi Seki, Shunsuke Kimura, Hideki Makishima, Nobuyuki Kakiuchi, Keisuke Kataoka, Tetsuichi Yoshizato, Hiroyuki Tsukamoto, Dai Nishijima, Takao Deguchi, Kentaro Ohki, Atsushi Sato, Hiroyuki Takahashi, Yoshiko Hashii, Sadao Tokimasa, Junichi Hara, Yoshiyuki Kosaka, Koji Kato, Takeshi Inukai, Junko Takita, Toshihiko Imamura, Satoru Miyano, Atsushi Manabe, Keizo Horibe, Seishi Ogawa, Masashi Sanada, BLOOD, 132, 2018年11月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Tolerable Dose of 6-Mercaptopurine and Prognostic Impact of NUDT15-Deficient Genotype in Childhood Acute Lymphoblastic Leukemia
Yoichi Tanaka, Motohiro Kato, Takaya Moriyama, Yuki Arakawa, Daisuke Hasegawa, Junya Fujimura, Dai Keino, Atsushi Sato, Takahiro Ueda, Yuichi Taneyama, Masatoshi Takagi, Masaki Yamamoto, Masaki Matsuoka, Moeko Hino, Hiroki Hori, Katsuyoshi Koh, Allen Eng Juh Yeoh, Jun J. Yang, Atsushi Manabe, BLOOD, 132, 2018年11月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Dasatinib-Combined Less Intensive Chemotherapy for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Down Syndrome
Hirabayashi Shinsuke, Yamamoto Shunsuke, Yamamoto Kaoru, Yamamoto Kazuki, Aiga Saori, Daida Atsuro, Ono Rintaro, Ashiarai Miho, Nishimura Akira, Hosoya Yosuke, Hasegawa Daisuke, Manabe Atsushi, PEDIATRIC BLOOD & CANCER, 65, S97, 2018年11月, ［査読有り］

Successful Inhaled Nitric Oxide Therapy for Severe Acute Respiratory Failure Due to Alveolar Hemorrhage During Induction Phase in AML M5
Ashiarai Miho, Umehara Naoki, Kuroko Yurika, Yamamoto Kaoru, Yamamoto Shunsuke, Ono Rintaro, Hirabayashi Shinsuke, Hosoya Yosuke, Hasegawa Daisuke, Manabe Atsushi, PEDIATRIC BLOOD & CANCER, 65, S55, S56, 2018年11月, ［査読有り］

小児T細胞性急性リンパ性白血病におけるNOTCH1シグナル活性化変異の種類と臨床的特徴の解析(Analysis of features of alterations leading to activate NOTCH1 signaling in pediatric T-ALL)　　　　　　　　　　　　　　　
木村 俊介, 関 正史, 吉田 健一, 上野 浩生, 塩澤 裕介, 磯部 知弥, 大木 健太郎, 加藤 元博, 康 勝好, 小林 良二, 出口 隆生, 橋井 佳子, 今村 俊彦, 佐藤 篤, 清河 信敬, 真部 淳, 堀部 敬三, 小原 明, 眞田 昌, 小林 正夫, 岡 明, 林 泰秀, 宮野 悟, 小川 誠司, 滝田 順子, 臨床血液, 59, 9, 1585, 1585, 2018年09月
(一社)日本血液学会-東京事務局, 英語

小児ALLにおける高用量メトトレキサート療法時の薬物クリアランスへ影響を及ぼす因子の検討(The between MTX clearance and genetic variants in high-dose MTX therapy for ALL)　　　　　　　　　　　　　　　
田中 庸一, 浦山 ケビン, 森 麻希子, 長谷川 大輔, 赤羽 弘資, 太田 節雄, 康 勝好, 真部 淳, 臨床血液, 59, 9, 1533, 1533, 2018年09月
(一社)日本血液学会-東京事務局, 英語

Clinical Sequencing of 347 Children with Acquired and Inherited Bone Marrow Failure Syndromes
Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Sayoko Doisaki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Masashi Sanada, Yoshiyuki Takahashi, Hitoshi Kanno, Hiroki Yamaguchi, Shouichi Ohga, Atsushi Manabe, Hideo Harigae, Shinji Kunishima, Eiichi Ishii, Masao Kobayashi, Kenichi Koike, Kenichiro Watanabe, Etsuro Ito, Minoru Takata, Miharu Yabe, Seishi Ogawa, Satoru Miyano, Seiji Kojima, BLOOD, 130, 2017年12月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Comprehensive Immunophenotyping Panel in Japan Enables to Detect Rare Subtypes in Childhood Leukemia
Takao Deguchi, Nobutaka Kiyokawa, Kentaro Ohki, Yoshiko Hashii, Atsushi Manabe, Souichi Adachi, Akiko Moriya Saito, Keizo Horibe, BLOOD, 130, 2017年12月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Integrated Genetic and Epigenetic Analysis in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
S. Kimura, M. Seki, T. Kawai, K. Yoshida, T. Isobe, H. Ueno, H. Suzuki, K. Oki, T. Imamura, N. Kiyokawa, M. Kobayashi, K. Koh, A. Manabe, A. Ohara, M. Sanada, Y. Hayashi, K. Hata, S. Miyano, S. Ogawa, J. Takita, PEDIATRIC BLOOD & CANCER, 64, S31, S31, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Close Correlation Between Immunophenotype and Genetic Abnormalities in Childhood Acute Lymphoblastic Leukemia: Results from TCCSG Study L04-16
Nobutaka Kiyokawa, Takashi Fukushima, Kentaro Ohki, Motohiro Kato, Takeshi Ishibashi, Ai Yoshimi, Yuya Saito, Takahiro Aoki, Kazuki Terada, Osamu Tomita, Keiko Onda, Yoshihiro Gocho, Shinsuke Hirabayashi, Daisuke Hasegawa, Hiroyuki Takahahsi, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara, PEDIATRIC BLOOD & CANCER, 64, S17, S17, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Multimodality Treatment for Pelvic Ewing Sarcoma
Akira Nishimura, Ayumu Arakawa, Yosuke Hosoya, Shinsuke Hirabayashi, Hiroki Yoshihara, Atsushi Kikuta, Seiichi Matsumoto, Jiro Kawamori, Daisuke Hasegawa, Tadashi Kumamoto, Chitose Ogawa, Atsushi Manabe, PEDIATRIC BLOOD & CANCER, 64, S58, S58, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Asymptomatic Cerebral Microhemorrhage in Adolescent and Young Adult Survivors of Childhood Cancer: Five Patients Examined Using Magnetic Resonance Imaging
Yosuke Hosoya, Yasushi Ishida, Miwa Ozawa, Taiki Nozaki, Kyoko Nagase, Michiyo Gunji, Kunie Maeda, Kyoko Kobayashi, Yuri Yoshimoto, Daisuke Hasegawa, Atsushi Manabe, Ryota Hosoya, PEDIATRIC BLOOD & CANCER, 64, S100, S100, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

The Feasibility of a Comprehensive Medical Check-up in Adolescent and Young Adult Survivors of Childhood Cancer
Miwa Ozawa, Yasushi Ishida, Kyoko Kobayashi, Kyoko Nagase, Michiyo Gunzi, Kunie Maeda, Yuri Yoshimoto, Yosuke Hosoya, Daisuke Hasegawa, Atsushi Manabe, Ryota Hosoya, PEDIATRIC BLOOD & CANCER, 64, S101, S101, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

The Association Between Plasma Methotrexate Concentration and Genetic Variant in High-dose Methotrexate Therapy for Childhood Acute Lymphoblastic Leukemia
Yoichi Tanaka, Kevin Urayama, Makiko Mori, Daisuke Hasegawa, Koshi Akahane, Setsuo Ota, Katsuyoshi Koh, Atsushi Manabe, PEDIATRIC BLOOD & CANCER, 64, S97, S98, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

IDH1 and KRAS Mutations are Involved in Acute Lymphoblastic Leukemia in Maffucci Syndrome
S. Hirabayashi, M. Seki, D. Hasegawa, M. Kato, N. Hyakuna, T. Shuo, S. Kimura, K. Yoshida, K. Kataoka, Y. Fujii, Y. Shiraishi, K. Chiba, H. Tanaka, N. Kiyokawa, S. Miyano, S. Ogawa, J. Takita, A. Manabe, PEDIATRIC BLOOD & CANCER, 64, S179, S180, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Correlation of Bone Marrow Morphology with Clinical Findings and Gene Alterations in Patients with Diamond-Blackfan Anemia
Asahito Hama, Tsutomu Toki, Akie Kobayashi, Hideki Muramatsu, Yusuke Okuno, Daisuke Hasegawa, Kazue Nozawa, Yoshiyuki Takahashi, Kenichiro Watanabe, Atsushi Manabe, Masafumi Ito, Etsuro Ito, Seiji Kojima, PEDIATRIC BLOOD & CANCER, 64, S28, S28, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Characteristics of Childhood Mixed Phenotype Acute Leukemia Diagnosed By Nation-Wide Immunophenotyping in Japan
Takao Deguchi, Nobutaka Kiyokawa, Kentaro Ohki, Yoshiko Hashii, Atsushi Manabe, Souichi Adachi, Akiko Saito, Keizou Horibe, PEDIATRIC BLOOD & CANCER, 64, S16, S16, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

遺伝性および後天性骨髄不全症候群の患者375名の臨床的配列決定
MURAMATSU Hideki, OKUNO Yusuke, YOSHIDA Kenichi, SHIRAISHI Yuichi, NARITA Atsushi, SAKAGUCHI Hirotoshi, KAWASHIMA Nozomu, XU Yinyan, CHIBA Kenichi, TANAKA Hiroko, HAMA Asahito, SANADA Masashi, SANADA Masashi, TAKAHASHI Yoshiyuki, KANNO Hitoshi, YAMAGUCHI Hiroki, OHGA Shouichi, MANABE Atsushi, HARIGAE Hideo, KUNISHIMA Shinji, ISHII Eiichi, KOBAYASHI Masao, KOIKE Kenichi, WATANABE Kenichiro, ITO Etsuro, TAKATA Minoru, YABE Miharu, MIYANO Satoru, OGAWA Seishi, KOJIMA Seiji, 臨床血液, 58, 9, 1519, 1519, 2017年09月
(一社)日本血液学会-東京事務局, 英語

日本における先天性赤血球産生異常性貧血の全エキソームシークエンス解析
HAMADA Motoharu, DOISAKI Sayoko, DOISAKI Sayoko, OKUNO Yusuke, MURAMATSU Hideki, HAMA Asahito, KATAOKA Shinsuke, ICHIKAWA Daisuke, TANIGUCHI Rieko, SUZUKI Kyogo, KOJIMA Daiei, SEKIYA Yuko, KAWASHIMA Nozomu, NARITA Atsushi, YOSHIDA Kenichi, SHIRAISHI Yuichi, SANADA Masashi, SANADA Masashi, CHIBA Kenichi, TANAKA Hiroko, MANABE Atsushi, TAGA Takashi, TAKAHASHI Yoshiyuki, MIYANO Satoru, OGAWA Seishi, KOJIMA Seiji, 臨床血液, 58, 9, 1477, 1477, 2017年09月
(一社)日本血液学会-東京事務局, 英語

"つつうらうら"の小児救急事情 小児救急医療の現況 多角的な視点から課題を共有する 当院の小児救急医療の10年間の動向 都市部の立場から　　　　　　　　　　　　　　　
梅原 直, 草川 功, 真部 淳, 小澤 美和, 稲井 郁子, 平田 倫生, 吉良 登志子, 山田 奈生子, 塙 佳生, 日原 真理子, 小森 信政, 渡辺 浩志, 小坂 和輝, 松藤 凡, 日本小児救急医学会雑誌, 16, 2, 232, 232, 2017年05月
(一社)日本小児救急医学会, 日本語

過去10年間に当院外来を受診した、異物・誤飲患児に関する検討　　　　　　　　　　　　　　　
山本 俊亮, 山本 薫, 相賀 咲央莉, 山本 一希, 梅原 直, 島袋 林秀, 平田 倫生, 小澤 美和, 真部 淳, 草川 功, 右田 美里, 松藤 凡, 日本小児救急医学会雑誌, 16, 2, 312, 312, 2017年05月
(一社)日本小児救急医学会, 日本語

ターゲットシーケンス解析を施行した小児造血不全移植例の解析
村松秀城, 奥野友介, 吉田健一, 白石友一, 濱麻人, 真田昌, 高橋義行, 菅野仁, 山口博樹, 大賀正一, 真部淳, 張替秀郎, 國島伸治, 石井榮一, 小林正夫, 小池健一, 渡邉健一郎, 伊藤悦朗, 高田穣, 矢部みはる, 小川誠司, 宮野悟, 小島勢二, 日本造血細胞移植学会総会プログラム・抄録集, 40th, 2017年

特発性造血障害に関する調査研究 先天性造血不全症候群の研究
中畑龍俊, 真部淳, 特発性造血障害に関する調査研究 平成28年度 総括・分担研究報告書(Web), 201610059A0012 (WEB ONLY), 2017年
日本語

Five Cases of Pediatric-Onset Bechet’s disease complicated with Myelodysplastic Syndrome.　　　　　　　　　　　　　　　
Kanamitsu K, Shimada A, Nishiuchi R, Shigemura T, Nakazawa Y, Koike K, Kodama Y, Shinkoda Y, Kawano Y, Yasui K, Sasaki K, Kajiwara R, Tsukahara H, Manabe A, International Journal of Hematology, 105, 3, 377, 382, 2017年

TAL1 Super Enhancer Aberration and Stil-TAL1 Fusion in Pediatric T Cell Acute Lymphoblastic Leukemia
Shunsuke Kimura, Masafumi Seki, Kenichi Yoshida, Hiroo Ueno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Hiromichi Suzuki, Keisuke Kataoka, Kentaro Ohki, Motohiro Kato, Katsuyoshi Koh, Ryoji Hanada, Nobutaka Kiyokawa, Masao Kobayashi, Atsushi Manabe, Akira Ohara, Yasuhide Hayashi, Satoru Miyano, Seishi Ogawa, Junko Takita, BLOOD, 128, 22, 2016年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Clusters of Childhood Mixed Phenotype Acute Leukemia Diagnosed By Nation-Wide Immunophenotyping in Japan
Takao Deguchi, Nobutaka Kiyokawa, Kentaro Ohki, Yoshiko Hashii, Atsushi Manabe, Souichi Adachi, Akiko M. Saito, Keizo Horibe, Yoshihiro Komada, BLOOD, 128, 22, 2016年12月
0, AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Genetic Abnormalities and Prognosis in Pediatric B-Precursor Acute Lymphoblastic Leukemia without Conventional Genetic Abnormalities; Tokyo Children's Cancer Study Group
Kenro Ohki, Shinsuke Hirabayashi, Akinori Yaguchi, Akinori Yaguchi, Kazuki Terada, Jun Ohkubo, Norio Shiba, Motohiro Kato, Takashi Fukushima, Katsuyoshi Koh, Hayashi Yasuhide, Atsushi Manabe, Akira Ohara, Nobutaka Kiyokawa, BLOOD, 128, 22, 2016年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Comparison of Clinical Outcomes Between Pediatric Aplastic Anemia and Refractory Cytopenia of Childhood
Asahito Hama, Atsushi Manabe, Daisuke Hasegawa, Kazue Nozawa, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi, Kenichiro Watanabe, Akira Ohara, Masafumi Ito, Seiji Kojima, BLOOD, 128, 22, 2016年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

TAL1 Abnormalities in Childhood T-Cell Acute Lymphoblastic Leukemia
M. Seki, K. Yoshida, S. Kimura, Y. Shiraishi, M. Kato, K. Koh, R. Hanada, T. Deguchi, T. Imamura, K. Horibe, N. Kiyokawa, A. Manabe, A. Ohara, M. Sanada, H. Mano, Y. Hayashi, S. Miyano, A. Oka, S. Ogawa, J. Takita, PEDIATRIC BLOOD & CANCER, 63, S117, S117, 2016年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

小児造血器腫瘍の分子遺伝学の進歩 : WHO分類第4版2016改訂 (特集 小児造血器腫瘍の特色 : 分子的理解から治療開発まで)
平林 真介, 真部 淳, 血液フロンティア, 26, 11, 1561, 1568, 2016年11月
医薬ジャーナル社, 日本語

Risk Factors for Psychosomatic Symptoms in Patients with Paediatric Cancers
D. Hasegawa, K. I. Maeda, K. Urayama, S. I. Tsujimoto, Y. Azami, M. Ozawa, A. Manabe, PEDIATRIC BLOOD & CANCER, 63, S280, S281, 2016年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

本邦での骨髄浸潤を伴わない小児顆粒球肉腫の後方視的研究(Retrospective study for pediatric myeloid sarcoma without bone marrow involvement in Japan)
多賀 崇, 今村 俊彦, 中島 健太郎, 前田 尚子, 渡辺 輝浩, 宮島 雄二, 藤村 純也, 佐野 仁志, 長谷川 大一郎, 河崎 裕英, 足立 壮一, 高木 正稔, 康 勝好, 真部 淳, 滝 智彦, 石田 也寸志, 日本小児血液, がん学会白血病リンパ腫委員会, 日本小児血液・がん学会雑誌, 53, 4, 251, 251, 2016年11月
(一社)日本小児血液・がん学会, 英語

mTOR阻害剤が有効であった血管奇形の3例　　　　　　　　　　　　　　　
平林 真介, 長谷川 大輔, 吉本 優里, 細谷 要介, 熊本 忠史, 真部 淳, 鮫島 麗子, 藤村 純也, 日本小児血液・がん学会雑誌, 53, 4, 282, 282, 2016年11月
(一社)日本小児血液・がん学会, 日本語

日本人小児ALLのL-アスパラギナーゼアレルギー発現におけるNFATC2 rs6021191多型の影響(Lack of association between L-asparaginase allergy and rs6021191 variant in NFATC2 in Japanese children with acute lymphoblastic leukemia)
田中 庸一, ウラヤマ・ケビン, 森 麻希子, 長谷川 大輔, 石丸 紗恵, 寺田 和樹, 柳町 昌克, 太田 節雄, 高橋 浩之, 外山 大輔, 慶野 大, 森脇 浩一, 高木 正稔, 藤村 純也, 関中 悠仁, 中村 こずえ, 佐藤 雄弥, 小原 明, 康 勝好, 真部 淳, 日本小児血液・がん学会雑誌, 53, 4, 342, 342, 2016年11月
(一社)日本小児血液・がん学会, 英語

改訂版長期フォローアップ手帳(Follow Up Diary)の使用感に関する全国調査(A nation-wide survey of usability assessment for the revised version of the "Long-Term Follow Up Diary")　　　　　　　　　　　　　　　
大園 秀一, 石田 也寸志, 清谷 知賀子, 岩井 艶子, 黒田 達夫, 藤 浩, 佐藤 伊織, 前田 美穂, 細井 創, 足立 壯一, 真部 淳, 福澤 正洋, 水谷 修紀, JCCG長期フォローアップ委員会, 日本小児血液・がん学会雑誌, 53, 4, 265, 265, 2016年11月
(一社)日本小児血液・がん学会, 英語

小児の特発性骨髄不全症候群の遺伝的背景
NARITA Atsushi, OKUNO Yusuke, MURAMATSU Hideki, YOSHIDA Kenichi, SHIRAISHI Yuichi, CHIBA Kenichi, TANAKA Hiroko, WANG Xinan, KAWASHIMA Nozomu, NISHIO Nobuhiro, HAMA Asahito, TAKAHASHI Yoshiyuki, HASEGAWA Daisuke, MANABE Atsushi, SAKAGUCHI Hirotoshi, YOSHIDA Nao, KATO Koji, MIYANO Satoru, ITO Masafumi, OGAWA Seishi, KOJIMA Seiji, 臨床血液, 57, 9, 1490, 1490, 2016年09月
(一社)日本血液学会-東京事務局, 英語

非血縁同種骨髄移植後に重症腎TMAを発症した骨髄異形成症候群の8歳女児例
宮本智史, 宮本智史, 木村俊介, 石田悠志, 代田惇朗, 松井俊大, 吉本優里, 平林真介, 細谷要介, 藤丸拓也, 長谷川大輔, 熊本忠史, 森慎一郎, 鈴木高祐, 真部淳, 日本造血細胞移植学会総会プログラム・抄録集, 38th, 2016年

小児最重症再生不良性貧血に対する非血縁者間臍帯血移植
木村俊介, 長谷川大輔, 松井俊大, 代田惇朗, 石田悠志, 吉本優里, 平林真介, 細谷要介, 吉原宏樹, 熊本忠史, 森愼一郎, 真部淳, 日本小児血液・がん学会雑誌(Web), 53, 1, 2016年

Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia : Swaminathan S. (Journal club : 抄読会(第52回))
吉本 優里, 真部 淳, 小児科臨床, 69, 1, 149, 152, 2016年01月
日本小児医事出版社, 日本語

日本人小児ALLのL-アスパラギナーゼアレルギー発現におけるNFATC2 rs6021191多型の影響
田中庸一, ウラヤマ ケビン, 森麻希子, 長谷川大輔, 石丸紗恵, 寺田和樹, 柳町昌克, 太田節雄, 高橋浩之, 外山大輔, 慶野大, 森脇浩一, 高木正稔, 藤村純也, 関中悠仁, 中村こずえ, 佐藤雄弥, 小原明, 康勝好, 真部淳, 日本小児血液・がん学会雑誌(Web), 53, 4, 2016年

本邦において2002年から2011年までに発生した2例の小児BCL2およびMYC dual-hit白血病
坂口公祥, 今村俊彦, 石丸紗恵, 今井千速, 下之段秀美, 岡田恵子, 出口隆生, 橋井佳子, 清河信敬, 齋藤明子, 真部淳, 佐藤篤, 康勝好, 日本小児血液・がん学会雑誌(Web), 53, 4, 2016年

小児造血器腫瘍に対する共通免疫学的診断パネルによって診断されたBilineal Leukemiaの特徴
出口隆生, 清河信敬, 大木健太郎, 橋井佳子, 真部淳, 足立壯一, 齋藤明子, 堀部敬三, 駒田美弘, 日本小児血液・がん学会雑誌(Web), 53, 4, 2016年

特発性造血障害に関する調査研究 先天性造血不全症候群の研究
中畑龍俊, 真部淳, 長谷川大輔, 小島勢二, 矢部普正, 小原明, 特発性造血障害に関する調査研究 平成27年度 総括・分担研究報告書, 45‐48, 2016年
日本語

The Outcome of Relapsed Childhood Core Binding Factor Acute Myeloid Leukemia: A Report from the JPLSG AML-05R Study
Hiroshi Moritake, Shiro Tanaka, Hideki Nakayama, Takako Miyamura, Shotaro Iwamoto, Akira Shimada, Kiminori Terui, Akiko M. Saito, Norio Shiba, Yasuhide Hayashi, Daisuke Tomizawa, Takashi Taga, Hiroaki Goto, Atsushi Manabe, Keizo Horibe, Shuki Mizutani, Souichi Adachi, BLOOD, 126, 23, 2015年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

TAL1 and MYB Abnormalities in Childhood T-Cell Acute Lymphoblastic Leukemia
Masafumi Seki, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Motohiro Kato, Shunsuke Kimura, Ryoji Hanada, Katsuyoshi Koh, Satoru Miyano, Toshihiko Imamura, Keizo Horibe, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara, Yasuhide Hayashi, Akira Oka, Seishi Ogawa, Junko Takita, BLOOD, 126, 23, 2015年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

The Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasms Presenting Leukemia Dissemination, Diagnosed By Nation-Wide Immunophenotyping for Pediatric Hematological Malignancy in Japan
Takao Deguchi, Nobutaka Kiyokawa, Yoshiko Hashii, Akiko M. Saito, Atsushi Manabe, Keizo Horibe, Yoshihiro Komada, BLOOD, 126, 23, 2015年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Genetic Susceptibility Loci for Childhood Acute Lymphoblastic Leukemia Among Japanese
Kevin Y. Urayama, Masatoshi Takagi, Takahisa Kawaguchi, Keitaro Matsuo, Yoichi Tanaka, Yuki Arakawa, Daisuke Hasegawa, Yuki Yuza, Takashi Kaneko, Yasushi Noguchi, Yuichi Taneyama, Setsuo Ota, Takeshi Inukai, Masakatsu Yanagimachi, Dai Keino, Kazutoshi Koike, Daisuke Toyama, Yozo Nakazawa, Hidernitsu Kurosawa, Kozue Nakamura, Koichi Moriwaki, Hiroaki Goto, Yujin Sekinaka, Daisuke Morita, Motohiro Kato, Katsuyoshi Koh, Yasushi Ishida, Akira Ohara, Shuki Mizutani, Fumihiko Matsuda, Atsushi Manabe, BLOOD, 126, 23, 2015年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

A novel recurrent EP300-ZNF384 gene fusion in B-cell precursor acute lymphoblastic leukemia
Y. Gocho, N. Kiyokawa, H. Ichikawa, K. Nakabayashi, T. Osumi, T. Ishibashi, H. Ueno, K. Terada, K. Oboki, H. Sakamoto, Y. Shioda, M. Imai, Y. Noguchi, Y. Arakawa, Y. Kojima, D. Toyama, K. Hata, T. Yoshida, K. Matsumoto, M. Kato, T. Fukushima, K. Koh, A. Manabe, A. Ohara, LEUKEMIA, 29, 12, 2445, 2448, 2015年12月
NATURE PUBLISHING GROUP, 英語, 速報，短報，研究ノート等（学術雑誌）

Comparison of Clinical and Laboratory Features Between Pediatric Aplastic Anemia and Refractory Cytopenia of Childhood
Asahito Hama, Atsushi Manabe, Daisuke Hasegawa, Hideki Muramatsu, Yoshiyuki Takahashi, Kenichiro Watanabe, Akira Ohara, Masafumi Ito, Seiji Kojima, BLOOD, 126, 23, 2015年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

FIVE CASES OF PEDIATRIC-ONSET BEHCET DISEASE COMPLICATED WITH MYELODYSPLASTIC SYNDROME
K. Kanamitsu, R. Nishiuchi, K. Yamato, T. Shigemura, Y. Nakazawa, K. Koike, Y. Shinkoda, Y. Kawano, H. Ueno, A. Manabe, K. Yasui, H. Goto, K. Sasaki, S. Yokota, A. Shimada, LEUKEMIA RESEARCH, 39, S96, S96, 2015年04月
PERGAMON-ELSEVIER SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

若年性骨髄単球性白血病(JMML)の急性転化
本田 裕子, 真部 淳, 血液内科, 70, 3, 397, 402, 2015年03月
科学評論社, 日本語

小児不応性血球減少症に対する造血幹細胞移植;日本小児血液学会前方視的登録例より
長谷川大輔, 平林真介, 渡辺静, 在家裕司, 土田昌宏, 増永敦子, 吉見礼美, 濱麻人, 小島勢二, 伊藤雅文, 中畑龍俊, 真部淳, 日本造血細胞移植学会総会プログラム・抄録集, 37th, 251, 2015年02月06日
日本語

非血縁者間臍帯血移植を行った小児最重症再生不良性貧血の1例
木村俊介, 長谷川大輔, 松井俊大, 小野沙裕子, 石田悠志, 吉本優里, 平林真介, 細谷要介, 吉原宏樹, 熊本忠志, 真部淳, 日本造血細胞移植学会総会プログラム・抄録集, 37th, 2015年

小児再生不良性貧血におけるリンパ球テロメア長と造血幹細胞移植予後との関連
成田敦, 坂口大俊, 関屋由子, 奥野友介, 村松秀城, 川島希, 土居崎小夜子, 濱麻人, 高橋義行, 吉田奈央, 伊藤雅文, 長谷川大輔, 真部淳, 矢部普正, 小林良二, 小島勢二, 日本造血細胞移植学会総会プログラム・抄録集, 37th, 2015年

特発性造血障害に関する調査研究 先天性造血不全症候群の研究
中畑龍俊, 真部淳, 小島勢二, 矢部普正, 小原明, 特発性造血障害に関する調査研究 平成26年度 総括・分担研究報告書, 76‐79, 2015年
日本語

SECONDARY CANCERS AFTER CANCER DIAGNOSIS IN CHILDHOOD: A HOSPITAL-BASED RETROSPECTIVE COHORT STUDY IN JAPAN
Y. Ishida, D. Qiu, M. Maeda, J. Fujimoto, H. Kigasawa, R. Kobayashi, M. Sato, J. Okamura, S. Yoshinaga, T. Rikiishi, H. Shichino, C. Kiyotani, K. Kudo, K. Asami, H. Hori, H. Kawaguchi, H. Inada, S. Adachi, A. Manabe, T. Kuroda, PEDIATRIC BLOOD & CANCER, 61, S198, S198, 2014年12月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Phase I/II Clinical Trial of Erwinia Asparaginase (Erwinase(R)) in Combination with Prednisolone, Vincristine and Pirarubicin in Children and Young Adults with Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL)
Chitose Ogawa, Atsushi Manabe, Hiroaki Goto, Katsuyoshi Koh, Daisuke Tomizawa, Keitaro Fukushima, Ken-ichiro Watanabe, Keizo Horibe, Atsushi Kikuta, Mitsuma Hamada, Akira Ohara, BLOOD, 124, 21, 2014年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Outcome of Adolescent and Young Adults with Acute Myeloid Leukemia Treated with Pediatric Protocols: A Report from the 3 Japanese Cooperative Studies
Daisuke Tomizawa, Tomoyuki Watanabe, Ryoji Hanada, Keizo Horibe, Yasuo Horikoshi, Shotaro Iwamoto, Akitoshi Kinoshita, Hiroshi Moritake, Hideki Nakayama, Akira Shimada, Takashi Taga, Hiroyuki Takahashi, Akio Tawa, Kiminori Terui, Hiroki Hori, Yoshifumi Kawano, Atsushi Kikuta, Atsushi Manabe, Souichi Adachi, BLOOD, 124, 21, 2014年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Central Morphology Review of Childhood Bone Marrow Failure in Japan
Asahito Hama, Manabe Atsushi, Daisuke Hasegawa, Kazue Nozawa, Yusuke Okuno, Masahiro Irie, Hideki Muramatsu, Yoshiyuki Takahashi, Kenichiro Watanabe, Akira Ohara, Masafumi Ito, Seiji Kojima, BLOOD, 124, 21, 2014年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

RISK FACTORS OF LONG-TERM CENTRAL VENOUS CATHETERS (CVCS) COMPLICATION IN CHILDREN WITH HEMATO-ONCOLOGICAL DISORDERS
A. Sakoda, T. Kawano, Y. Hosoya, H. Yoshiwara, S. Hirabayashi, D. Hasegawa, M. Ozawa, H. Matsufuji, A. Manabe, O. Takahashi, PEDIATRIC BLOOD & CANCER, 61, S353, S353, 2014年12月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Genetic Abnormalities and Prognosis in Pediatric B-precursor Acute Lymphoblastic Leukemia Treated on Tokyo Children's Cancer Study Group Protocol
Kentaro Ohki, Myoung-ja Park, Yusuke Hara, Norio Shiba, Takashi Fukushima, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara, Nobutaka Kiyokawa, Yasuhide Hayashi, BLOOD, 124, 21, 2014年12月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

小児急性リンパ性白血病における6-メルカプトプリン/メトトレキサート関連遺伝子の再発リスクへの影響(The influence of genetic polymorphisms related with 6-mercaptopurine and methotrexate on the risk of relapse in childhood acute lymphoblastic leukemia)
田中 庸一, 真部 淳, 中舘 尚也, 慶野 大, 中村 こずえ, 康 勝好, 秋山 政晴, 植田 高弘, 小宮山 貴子, 日本小児血液・がん学会雑誌, 51, 4, 235, 235, 2014年10月
(一社)日本小児血液・がん学会, 英語

B前駆細胞性急性リンパ芽球性白血病の新規融合遺伝子EP300-ZNF384 BCP-ALLの新たなサブグループ(Identification of a novel subset of B-cell precursor acute lymphoblastic leukemia with EP300-ZNF384 fusion gene)
牛腸 義宏, 清河 信敬, 市川 仁, 中林 一彦, 上野 瞳, 大隅 朋生, 石橋 武士, 寺田 和樹, 大保木 啓介, 坂本 裕美, 塩田 曜子, 今井 雅子, 野口 靖, 外山 大輔, 秦 健一郎, 吉田 輝彦, 松本 健治, 福島 敬, 康 勝好, 真部 淳, 小原 明, 日本小児血液・がん学会雑誌, 51, 4, 238, 238, 2014年10月
(一社)日本小児血液・がん学会, 英語

小児Ph-like ALL症例の表面マーカー、遺伝子発現解析
飯島 一智, 清河 信敬, 吉原 宏樹, 富田 理, 小林 健一郎, 福島 敬, 林 泰秀, 菊地 陽, 康 勝好, 真部 淳, 小原 明, 日本小児血液・がん学会雑誌, 51, 3, 200, 205, 2014年09月
近年、B前駆細胞性急性リンパ芽球性白血病(BCP-ALL)症例の中で、BCR-ABL1陰性にもかかわらずPh1 ALLに類似した遺伝子発現プロファイルを示し、予後も同程度不良な亜群であるPh-like ALLが注目されている。現状では多数の症例の遺伝子発現データに基づいたクラスタリング解析により判定されていることから、より簡便、迅速に症例毎に適用可能な診断法が求められている。我々はGene Set Enrichment Analysisを用いて単一症例でのPh-like ALL判定法を確立し、東京小児がん研究グループ(TCCSG)ALL治療研究L0416/0616登録BCP-ALL 235例に対してマイクロアレイによる遺伝子発現解析を行ない、14例(6.0%)がPh-like ALLと判断され、予後不良であることを報告している。そこで、今回はフローサイトメトリーによるマーカー所見と遺伝子発現に基づき、特異的マーカーの探索を行なった。表面マーカー所見としては、全例がCD10陽性のcommon-ALL型で、約7割の症例でCD66cが陽性であった。種々のMyeloid系マーカーのaberrantな発現を認めたものの、マーカー所見のみでPh-like ALLを判定するのは困難であった。また、Ph-like ALLとPh1 ALL症例に共通して特徴的に発現する遺伝子やPh-like ALLのみで特徴的に発現する遺伝子を同定した。(著者抄録), (一社)日本小児血液・がん学会, 日本語

INVESTIGATION OF PH-LIKE ALL BY GENE SET ENRICHMENT ANALYSIS AND IDENTIFICATION OF THEIR SPECIFIC EXPRESSION GENES
K. Iijima, N. Kiyokawa, K. Nakabayashi, H. Ichikawa, T. Osumi, H. Yoshihara, K. Ohki, M. Kato, T. Fukushima, H. Shimada, T. Mori, A. Kinoshita, K. Matsumoto, K. Koh, A. Kikuchi, Y. Hayashi, A. Manabe, A. Ohara, HAEMATOLOGICA, 99, 5, 5, 2014年06月
FERRATA STORTI FOUNDATION, 英語, 研究発表ペーパー・要旨（国際会議）

点鼻あるいは経口デスモプレシン製剤を用いて化学療法中の尿崩症を管理した神経下垂体部胚細胞腫 (特集 小児内分泌学の進歩2015) -- (成長・下垂体)
木村 俊介, 伊藤 純子, 吉本 優里, 平林 真介, 細谷 要介, 吉原 宏樹, 長谷川 大輔, 真部 淳, ホルモンと臨床, 62, 5, 367, 371, 2014年05月
医学の世界社, 日本語

小児急性リンパ性白血病のキメラ遺伝子スクリーニング検査　　　　　　　　　　　　　　　
大木 圭子, 南木 融, 福島 敬, 清河 信敬, 康 勝好, 小原 明, 真部 淳, 川上 康, 医学検査, 63, 学会特集号, 175, 175, 2014年04月
(一社)日本臨床衛生検査技師会, 日本語

点鼻あるいは経口デスモプレシン製剤を用いて化学療法中の尿崩症を管理した神経下垂体部胚細胞腫瘍の5例
木村俊介, 細谷要介, 石田悠志, 野村耕太郎, 吉本優里, 吉原宏樹, 長谷川大輔, 伊藤純子, 真部淳, 日本小児内分泌学会学術集会プログラム・抄録集, 48th, 2014年

変異KRASの片親性ダイソミーにより急性転化したJMML
加藤 元博, 安井 直子, 関 正史, 岸本 宏志, 佐藤 亜以子, 長谷川 大輔, 清河 信敬, 小川 誠司, 真部 淳, 滝田 順子, 康 勝好, 花田 良二, 日本小児血液・がん学会雑誌, 50, 4, 651, 651, 2013年12月
(一社)日本小児血液・がん学会, 日本語

B前駆細胞性ALL再発症例のマーカーの特徴に関する検討　　　　　　　　　　　　　　　
牛腸 義宏, 清河 信敬, 富田 理, 飯島 一智, 吉原 宏樹, 石橋 武士, 小林 健一郎, 福島 敬, 前田 美穂, 林 泰秀, 菊地 陽, 康 勝好, 真部 淳, 小原 明, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 202, 202, 2013年11月
(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 日本語

小児B前駆細胞型ALLにおけるEBF1-PDGFRB融合遺伝子の解析 TCCSG-ALL研究　　　　　　　　　　　　　　　
大木 健太郎, 朴 明子, 原 勇介, 柴 徳生, 大喜多 肇, 小林 健一郎, 外松 学, 福島 敬, 康 勝好, 花田 良二, 真部 淳, 菊地 陽, 土田 昌宏, 小原 明, 清河 信敬, 林 泰秀, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 244, 244, 2013年11月
(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 日本語

変異KRASの片親性ダイソミーにより急性転化したJMML
加藤 元博, 安井 直子, 関 正史, 岸本 宏志, 佐藤 亜以子, 長谷川 大輔, 清河 信敬, 小川 誠司, 真部 淳, 滝田 順子, 康 勝好, 花田 良二, 日本小児血液・がん学会雑誌, 50, 3, 496, 496, 2013年10月
(一社)日本小児血液・がん学会, 日本語

小児のMDSと再生不良性貧血 : 最近の動向
上野 浩生, 真部 淳, 血液内科, 67, 3, 404, 410, 2013年09月
科学評論社, 日本語

REAPPRAISAL OF NCI/ROME CRITERIA IN CHILDHOOD B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA: TOKYO CHILDREN'S CANCER STUDY GROUP STUDIES BETWEEN 1989 AND 2003
A. Manabe, K. Koh, K. Oshima, J. Fujimura, K. Ikuta, T. Saito, A. Kikuchi, R. Hanada, M. Tsuchida, A. Ohara, PEDIATRIC BLOOD & CANCER, 60, 66, 66, 2013年09月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

HYPERSENSITIVITY TO ASPARAGINASE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
D. Hasegawa, S. Watanabe, H. Yoshihara, Y. Hosoya, C. Ogawa, K. Goto, R. Hosoya, A. Manabe, PEDIATRIC BLOOD & CANCER, 60, 63, 63, 2013年09月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

NURSING CARE FOR CHILDREN WITH DOWN SYNDROME (DS) AND LEUKEMIA
J. Iida, M. Hirata, D. Hasegawa, A. Sekitomi, Y. Toriyama, W. Irie, R. Nishino, M. Ozawa, A. Manabe, R. Hosoya, PEDIATRIC BLOOD & CANCER, 60, 41, 41, 2013年09月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

小児Ph-like ALLのマーカー所見の検討　　　　　　　　　　　　　　　
清河 信敬, 飯島 一智, 富田 理, 吉原 宏樹, 三春 晶嗣, 大隅 朋生, 嶋田 博之, 福島 敬, 森 鉄也, 斎藤 正博, 康 勝好, 真部 淳, 菊地 陽, 林 泰秀, 小原 明, Cytometry Research, 23, Suppl., 57, 57, 2013年06月
(一社)日本サイトメトリー学会, 日本語

Cytomtric Bead Arrayを用いたBCR-ABL1蛋白検出の臨床的有用性　　　　　　　　　　　　　　　
富田 理, 清河 信敬, 三春 晶嗣, 石橋 武士, 大隅 朋生, 嶋田 博之, 福島 敬, 森 鉄也, 斎藤 正博, 康 勝好, 真部 淳, 菊地 陽, 林 泰秀, 小原 明, Cytometry Research, 23, Suppl., 58, 58, 2013年06月
(一社)日本サイトメトリー学会, 日本語

Morphological differentiation of bone marrow failure syndromes in children according to 2008 WHO classification
A. Hama, A. Manabe, M. Ito, D. Hasegawa, K. Nozawa, H. Muramatsu, Y. Takahashi, A. Ohara, S. Kojima, LEUKEMIA RESEARCH, 37, S89, S89, 2013年05月
PERGAMON-ELSEVIER SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Equivalent outcome between reduced-intensity versus conventional myeloablative conditioning haematopoietic stem cell transplantation for childhood MDS: a report from the MDS working group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT)
D. Hasegawa, A. Kikuchi, M. Yabe, M. Kato, K. Kudo, Y. Atsuta, J. Inagaki, M. Inoue, R. Nishimura, J. Tanaka, K. Kato, H. Yabe, K. Kawa, A. Manabe, K. Watanabe, BONE MARROW TRANSPLANTATION, 48, S296, S297, 2013年04月
NATURE PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

思春期がん経験者のQOLと病気に関する自己開示
三井 千佳, 山崎 あけみ, 前田 尚子, 堀部 敬三, 浅見 恵子, 原 純一, 井田 孔明, 康 勝好, 小澤 美和, 真部 淳, 上別府 圭子, 日本小児血液・がん学会雑誌, 50, 1, 79, 84, 2013年04月
思春期がん経験者31名を対象に病気に関する自己開示とQOLについての調査を行った。開示相手として診断当時は母親を、現在は母親と友人を選択している者が多かった。診断当時も現在も「結婚・子どもを持つこと」が最も開示していない内容であった。また診断当時も現在も開示していること、またはしていないことについて概ね満足しており、現在の満足度の高さが精神的健康を高める可能性が示唆された。(著者抄録), (一社)日本小児血液・がん学会, 日本語

多発性骨浸潤で発症したバーキットリンパ腫の1症例
田中 千絵, 野沢 和江, 佐野 彬子, 内川 香織, 中島 篤子, 真部 淳, 武田 京子, 臨床病理, 61, 3, 231, 236, 2013年03月25日
日本臨床検査医学会事務所 ; 1953-, 日本語

小児B前駆細胞型ALLにおけるCRLF2高発現例の特徴 TCCSG-ALL研究　　　　　　　　　　　　　　　
大木 健太郎, 朴 明子, 柴 徳生, 清河 信敬, 康 勝好, 花田 良二, 真部 淳, 菊地 陽, 小原 明, 林 泰秀, 日本小児科学会雑誌, 117, 2, 345, 345, 2013年02月
(公社)日本小児科学会, 日本語

小児不応性血球減少症の臨床像の検討 日本小児血液学会前方視的登録例より　　　　　　　　　　　　　　　
長谷川 大輔, 在家 裕司, 土田 昌宏, 増永 敦子, 吉見 礼美, 濱 麻人, 小島 勢二, 伊藤 雅文, 中畑 龍俊, 真部 淳, 日本小児血液, がん学会MDS委員会, 日本小児科学会雑誌, 117, 2, 370, 370, 2013年02月
(公社)日本小児科学会, 日本語

血球貪食症候群の経過中に中枢神経症状を呈した3例の画像的考察
石田悠志, 長谷川大輔, 野崎太希, 細谷要介, 吉原宏樹, 平林真介, 神谷尚宏, 熊本忠史, 小川千登世, 細谷亮太, 森愼一郎, 真部淳, 日本小児血液・がん学会学術集会・日本小児がん看護学会・がんの子供を守る会公開シンポジウムプログラム・総会号, 55th-11th-18th, 2013年

後天性再生不良性貧血に対する免疫抑制療法の予測因子としてのテロメア長
SAKAGUCHI Hirotoshi, NISHIO Nobuhiro, KAWASHIMA Nozomu, WANG Xinan, NARITA Atsushi, DOISAKI Sayoko, MURAMATSU Hideki, HAMA Asahito, NAKANISHI Koji, TAKAHASHI Yoshiyuki, TSUCHIDA Masahiro, KOBAYASHI Ryouji, ITOU Etsurou, YABE Hiromasa, OHGA Syouichi, OHARA Akira, HASEGAWA Daisuke, MANABE Atsushi, ITOU Masafumi, KOJIMA Seiji, 臨床血液, 54, 9, 2013年

【臨床血液学 今後の展望(2013年版)-リンパ系疾患-】 小児急性リンパ性白血病　　　　　　　　　　　　　　　
真部 淳, 長谷川 大輔, 臨床血液, 54, 1, 100, 108, 2013年01月
(一社)日本血液学会-東京事務局, 日本語

POSTTRAUMATIC STRESS SYMPTOMS AS AN IMPORTANT REACTION IN CHILDREN WHO DONATE THEIR STEM CELL TO THEIR SIBLINGS WITH CANCER
Miwa Ozawa, Asuka Higashi, Akiko Kobayashi, Disuke Hasegawa, Chitose Ogawa, Atsushi Manabe, Ryota Hosoya, ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 8, 247, 247, 2012年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

CD66c陽性小児急性リンパ芽球性白血病の特徴　　　　　　　　　　　　　　　
富田 理, 清河 信敬, 三春 晶嗣, 小林 健一郎, 大喜多 肇, 長谷川 大輔, 嶋田 博之, 森 鉄也, 福島 敬, 斎藤 正博, 犬飼 岳史, 康 勝好, 杉田 完爾, 花田 良二, 土田 昌宏, 真部 淳, 菊地 陽, 藤本 純一郎, 林 泰秀, 小原 明, 東京小児がん研究グループ, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 286, 286, 2012年11月
(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 日本語

経過中に急性転化したJMML 23例の検討 MDS委員会のデータベースから　　　　　　　　　　　　　　　
本田 裕子, 土田 昌宏, 増永 敦子, 吉見 礼美, 小島 勢二, 伊藤 雅文, 菊地 陽, 中畑 龍俊, 真部 淳, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 251, 251, 2012年11月
(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 日本語

ダウン症候群に合併した一過性骨髄異常増殖症に対する少量シタラビン療法による腫瘍崩壊症候群　　　　　　　　　　　　　　　
村松 秀城, 菊地 陽, 林 泰秀, 川村 眞智子, 小島 勢二, 矢部 みはる, 磯山 恵一, 滝 智彦, 辻 浩一郎, 土田 昌宏, 真部 淳, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 54回・10回・17回, 282, 282, 2012年11月
(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, 日本語

【MDS(骨髄異形成症候群)】 小児のMDS
長谷川 大輔, 真部 淳, 臨床検査, 56, 12, 1377, 1384, 2012年11月
(株)医学書院, 日本語

若年性骨髄単球性白血病(JMML)の分子機構と治療
真部 淳, 臨床血液, 53, 8, 729, 733, 2012年08月30日
日本語

Congenital Dyserythropoietic Anemia : 現状と今後の課題
多賀 崇, 真部 淳, 日本小児科学会雑誌, 116, 7, 1075, 1080, 2012年07月01日
日本小児科学会, 日本語

FCMによるリンパ系腫瘍への新たなアプローチ 小児白血病MRD検出における10カラーフローサイトメトリーの有用性　　　　　　　　　　　　　　　
三春 晶嗣, 清河 信敬, 小林 健一郎, 大喜多 肇, 飯島 一智, 森 鉄也, 斎藤 正博, 福島 敬, 康 勝好, 真部 淳, 菊地 陽, 林 泰秀, 小原 明, Cytometry Research, 22, Suppl., 44, 44, 2012年06月
(一社)日本サイトメトリー学会, 日本語

小児リンパ芽球性白血病のキメラ遺伝子、細胞マーカーと遺伝子発現プロファイルの特徴　　　　　　　　　　　　　　　
清河 信敬, 福島 敬, 小林 健一郎, 三春 晶嗣, 大喜多 肇, 飯島 一智, 森 鉄也, 斎藤 正博, 康 勝好, 真部 淳, 菊地 陽, 林 泰秀, 小原 明, Cytometry Research, 22, Suppl., 66, 66, 2012年06月
(一社)日本サイトメトリー学会, 日本語

A case of Langerhans cell histiocytosis with severe anemia: Letterer-Siwe disease
Hitomi Nakamura, Yukari Zenke, Yoko Momose, Mamiko Masuzawa, Satoru Arai, Hikaru Eto, Atsushi Manabe, Yosuke Hosoya, Daisuke Hasegawa, JOURNAL OF DERMATOLOGY, 39, 118, 118, 2012年06月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

がんを家族にどう伝えどう支えるか 乳がん患者の子どものこころ　　　　　　　　　　　　　　　
小澤 美和, 三浦 絵莉子, 石田 也寸志, 山内 英子, 真部 淳, 日本緩和医療学会学術大会プログラム・抄録集, 17回, 206, 206, 2012年06月
(NPO)日本緩和医療学会, 日本語

小児がん経験者の晩期合併症の予測は可能か 聖路加国際病院小児科の経験
石田 也寸志, 渡辺 静, 小澤 美和, 米川 聡子, 小川 千登世, 長谷川 大輔, 細谷 要介, 吉原 宏樹, 真部 淳, 森本 克, 西村 昴三, 細谷 亮太, 日本小児血液・がん学会雑誌, 49, 1-2, 31, 39, 2012年05月
JPLSG長期フォローアップ(FU)委員会の5段階のFUレベルが、晩期合併症発症の予想に役立つかどうか検証した。【対象と方法】研究デザインはレトロスペクティブコホート研究で、対象は1972年から2011年に当院小児科で診療した小児がん症例で治療を終了しているものである。治療終了時FUレベルと最終観察日の晩期合併症について単変量とロジステック解析を行いオッズ比(OR)を求めた。【結果】2011年3月31日の時点で生存していた388例で、FUレベル判定不能88例を除き、残り300例を解析した。血液がんではレベル3=41%、4=37%、脳腫瘍はレベル4=100%、固形腫瘍はレベル2=25%、レベル3=44%、LCHはレベル1=62%、骨軟部腫瘍はレベル3=36%、4=25%、5=40%であった。晩期合併症は、レベル1:0%、レベル2:15%、レベル3:37%、レベル4:72%、レベル5:100%で、ロジスティク解析では、脳腫瘍(OR:65.4)、固形腫瘍(OR:3.45)、骨軟部腫瘍(OR:10.4)、最終観察年齢26歳以上(OR:6.75)、CPM>5g/m2(OR:5.64)、同種造血細胞移植(OR:10.9)が晩期合併症の独立したリスク因子であった。【結語】治療終了時の5段階のFUレベル評価は晩期合併症の予測に有用であり、この分類を活用することによりリスクに基づいたFU計画の立案が可能である。(著者抄録), (NPO)日本小児血液・がん学会, 日本語

血液腫瘍(白血病,悪性リンパ腫) (特集 小児慢性疾患の生活指導 : 最新の知見から) -- (日常生活における管理・指導)
細谷 要介, 真部 淳, 小児科臨床, 65, 4, 615, 621, 2012年04月
日本小児医事出版社, 日本語

小児ALLにおけるTP53遺伝子異常の意義
熊本 忠史, 真部 淳, 血液内科, 64, 4, 508, 512, 2012年04月
科学評論社, 日本語

Wiskott-Aldrich syndrome presenting with a clinical picture resembling juvenile myelomonocytic leukaemia
A. Yoshimi, Y. Kamachi, K. Imai, T. Morio, N. Watanabe, A. Konoshita, N. Nakadate, K. Tamura, S. Oozono, R. Kobayashi, H. Kigasawa, M. Jakob, S. Nonoyama, A. Manabe, C. Niemeyer, S. Kojima, BONE MARROW TRANSPLANTATION, 47, S69, S70, 2012年04月
NATURE PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

プライマリケア・マスターコース 小児科診療のすすめ 小児がん
真部 淳, 細谷 亮太, 日本医事新報, 4586, 46, 49, 2012年03月17日
日本医事新報社, 日本語

若年性骨髄単球性白血病75例の予後 小児血液学会MDS委員会の前方視的検討　　　　　　　　　　　　　　　
吉田 奈央, 平林 真介, 渡辺 静, 在家 裕司, 土田 昌宏, 吉見 礼美, 増永 敦子, 大塚 欣敏, 伊藤 雅文, 小島 勢二, 中畑 龍俊, 真部 淳, 臨床血液, 52, 12, 1853, 1858, 2011年12月
若年性骨髄単球性白血病(JMML)は乳幼児に好発する稀な骨髄異形成/骨髄増殖性疾患であり,診断が難しいことから小児血液学会MDS委員会において前方視的登録と中央診断を行っている。今回1999年から2006年に本登録を経て診断されたJMML75例を追跡調査した。診断時年齢は中央値20ヵ月(1〜85ヵ月),染色体異常は21例に認め,うち11例がmonosomy7を有した。全体の5年生存率は60%であり,61例で造血幹細胞移植が施行された。移植前処置は多岐にわたり,移植片は骨髄43,末梢血5,臍帯血13例であった。移植例の5年生存率は61%であり,臍帯血移植群の生存率は他の群に比べ有意に低かった(38% vs. 68%;P=0.03)。前方視的登録による症例把握の結果を受け,日本小児白血病リンパ腫研究グループ(JPLSG)では標準的移植法の確立を目的とした多施設共同臨床試験JMML11を計画している。(著者抄録), (一社)日本血液学会-東京事務局, 日本語

左上腹部痛を主訴に胸椎圧迫骨折を呈した9歳女児 (特集 症例に学ぶ--小児放射線カンファレンス) -- (中枢神経系・脊椎)
槇殿 文香理, 野崎 太希, 真部 淳, 小児科診療, 74, 11, 1665, 1669, 2011年11月
診断と治療社, 日本語

上腕部の腫脹を呈した8歳女児 (特集 症例に学ぶ--小児放射線カンファレンス) -- (骨軟部)
野崎 太希, 槇殿 文香理, 真部 淳, 小児科診療, 74, 11, 1835, 1839, 2011年11月
診断と治療社, 日本語

発熱,移動する関節痛を主訴として多発骨病変を呈した10歳代男児 (特集 症例に学ぶ--小児放射線カンファレンス) -- (骨軟部)
槇殿 文香理, 野崎 太希, 真部 淳, 小児科診療, 74, 11, 1846, 1850, 2011年11月
診断と治療社, 日本語

A Brief Use of Imatinib Immediately Before Hematopoietic Stem Cell Transplantation (HSCT) in Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph plus ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph+ALL04
Atsushi Manabe, Hirohide Kawasaki, Motoaki Chin, Atsushi Sato, Kimikazu Matsumoto, Tsutomu Watanabe, Michiko Kajiwara, Hiroyuki Shimada, Itaru Kato, Yuichi Kodama, Noriko Sato, Kazuko Kudo, Atsushi Kikuta, Megumi Oda, Tomoyuki Watanabe, Akiko M. Saito, Masahito Tsurusawa, Keizo Horibe, BLOOD, 118, 21, 1095, 1096, 2011年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Acute Lymphoblastic Leukemia in Children with Down Syndrome: A Report From the Ponte Di Legno Study Group
Trudy Buitenkamp, Shai Izraeli, Martin Zimmermann, Erik Forestier, Nyla A. Heerema, Marry M. van den Heuvel, Rob Pieters, Valerie de Haas, Lewis B. Silverman, Kjeld Schmiegelow, Der-Cherng Liang, Keizo Horibe, Maurizio Arico, Giovanni Cazzaniga, Giuseppe Basso, Karen R. Rabin, Martin Schrappe, Gunnar Cario, Georg Mann, Veerle Mondelaers, Tim Lammens, Helene Cave, Batia Stark, Anthony V. Moorman, Ajay J. Vora, Stephen Hunger, Ching-Hon Pui, Charles G. Mullighan, Atsushi Manabe, Gabriele Escherich, Jerzy Kowalczyk, James A. Whitlock, Christian M. Zwaan, BLOOD, 118, 21, 1527, 1528, 2011年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

TCCSG ALL登録症例の細胞抗原とキメラ遺伝子との関連性についての検討　　　　　　　　　　　　　　　
小林 健一郎, 福島 敬, 南木 融, 清河 信敬, 三春 晶嗣, 山田 浩之, 飯島 一智, 大喜多 肇, 森 鉄也, 熊谷 昌明, 藤本 純一郎, 斎藤 正博, 康 勝好, 真部 淳, 菊地 陽, 林 泰秀, 土田 昌宏, 小原 明, 東京小児がん研究グループTCCSG, 小児がん, 48, プログラム・総会号, 212, 212, 2011年11月
(NPO)日本小児がん学会, 日本語

東京小児がん研究グループ(TCCSG)ALL治療研究登録症例の網羅的遺伝子発現解析　　　　　　　　　　　　　　　
飯島 一智, 清河 信敬, 小林 健一郎, 大喜多 肇, 山田 浩之, 三春 晶嗣, 森 鉄也, 福島 敬, 南木 融, 斎藤 正博, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 藤本 純一郎, 林 泰秀, 土田 昌宏, 小原 明, 東京小児がん研究グループTCCSG, 小児がん, 48, プログラム・総会号, 211, 211, 2011年11月
(NPO)日本小児がん学会, 日本語

10カラーフローサイトメトリーを用いたB前駆細胞急性リンパ芽球性白血病のMRD検出　　　　　　　　　　　　　　　
三春 晶嗣, 清河 信敬, 小林 健一郎, 大喜多 肇, 山田 浩之, 飯島 一智, 森 鉄也, 福島 敬, 斎藤 正博, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 藤本 純一郎, 林 泰秀, 土田 昌宏, 小原 明, 東京小児がん研究グループTCCSG, 小児がん, 48, プログラム・総会号, 247, 247, 2011年11月
(NPO)日本小児がん学会, 日本語

小児ALLにおけるCRLF2、IKZF1、JAK2遺伝子の臨床的意義 TCCSGの小児B前駆細胞型急性リンパ性白血病におけるCRLF2とIKZF1の解析　　　　　　　　　　　　　　　
大木 健太郎, 大喜多 肇, 小林 健一郎, 清河 信敬, 朴 明子, 新井 心, 外松 学, 柴 徳生, 福島 敬, 康 勝好, 花田 良二, 真部 淳, 菊地 陽, 小原 明, 土田 昌宏, 林 泰秀, 小児がん, 48, プログラム・総会号, 174, 174, 2011年11月
(NPO)日本小児がん学会, 日本語

若い乳がん患者とその子どもへのサポートを考える 子どもの行動・情緒的問題<続報>　　　　　　　　　　　　　　　
小澤 美和, 三浦 絵莉子, 石田 智美, 石田 也寸志, 真部 淳, 山内 英子, 日本乳癌学会総会プログラム抄録集, 19回, 428, 428, 2011年09月
(一社)日本乳癌学会, 日本語

日本におけるL-asparaginase(L-asp)療法中の凝固障害に対する支持療法の調査(Survey of supportive therapy for coagulation disorder during L-asparaginase (L-asp) therapy in Japan)　　　　　　　　　　　　　　　
Ogawa Chitose, Manabe Atsushi, Ohara Akira, Ishiguro Akira, 臨床血液, 52, 9, 1078, 1078, 2011年09月
(一社)日本血液学会-東京事務局, 英語

日本人小児における血栓症に関する初の全国調査(The first national survey of thrombotic disorders in Japanese children)　　　　　　　　　　　　　　　
Ishiguro Akira, Taki Masashi, Manabe Atsushi, Ogawa Chitose, Nakadate Hisaya, Shima Midori, 臨床血液, 52, 9, 1138, 1138, 2011年09月
(一社)日本血液学会-東京事務局, 英語

The survey of supportive therapy for coagulation disorder during L-asparaginase (L-ASP) therapy in Japan
C. Ogawa, A. Manabe, A. Ohara, A. Ishiguro, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 9, 227, 227, 2011年07月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

小児白血病におけるCD66c発現の意義　　　　　　　　　　　　　　　
山田 浩之, 清河 信敬, 橋本 亙, 飯島 一智, 嶋 晴子, 嶋田 博之, 森 鉄也, 福島 敬, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 小原 明, 林 泰秀, 土田 昌宏, Cytometry Research, 21, Suppl., 78, 78, 2011年06月
(一社)日本サイトメトリー学会, 日本語

カラーフローサイトメトリーを用いた小児白血病MRD検出の試み　　　　　　　　　　　　　　　
清河 信敬, 三春 晶嗣, 山田 浩之, 橋本 亙, 飯島 一智, 森 鉄也, 斎藤 正博, 福島 敬, 康 勝好, 真部 淳, 菊地 陽, 熊谷 昌明, 林 泰秀, 土田 昌宏, 小原 明, Cytometry Research, 21, Suppl., 80, 80, 2011年06月
(一社)日本サイトメトリー学会, 日本語

特発性造血障害に関する調査研究 小児の骨髄不全と骨髄異形成症候群に関する研究
中畑龍俊, 真部淳, 特発性造血障害に関する調査研究 平成22年度 総括・分担研究報告書, 39, 45, 2011年
日本語

東京小児がん研究グループ急性リンパ性白血病治療研究におけるBCP-ALL-NCI-HR群の治療成績 特に年齢因子の検討　　　　　　　　　　　　　　　
藤村 純也, 高橋 浩之, 菊地 陽, 清河 信敬, 福島 敬, 康 勝好, 真部 淳, 花田 良二, 小原 明, 土田 昌宏, 小児がん, 47, プログラム・総会号, 396, 396, 2010年12月
(NPO)日本小児がん学会, 日本語

ダウン症候群に合併した一過性骨髄異常増殖症148例の後方視的解析　　　　　　　　　　　　　　　
村松 秀城, 菊地 陽, 林 泰秀, 川村 眞智子, 小島 勢二, 矢部 みはる, 磯山 恵一, 滝 智彦, 辻 浩一郎, 土田 昌宏, 真部 淳, 小児がん, 47, プログラム・総会号, 221, 221, 2010年12月
(NPO)日本小児がん学会, 日本語

Low-Dose Cytosine Arabinoside Therapy for Neonates with Down Syndrome (DS) and Transient Leukemia (TL)
Hideki Muramatsu, Yasuhide Hayashi, Machiko Kawamura, Seiji Kojima, Miharu Yabe, Keiichi Isoyama, Tomohiko Taki, Kohichiro Tsuji, Masahiro Tsuchida, Atsushi Manabe, Etsuro Ito, Shotaro Iwamoto, Hiromi Kato, Aiko Sumie, Takashi Taga, Keiko Nomura, Daisuke Hasegawa, Ken-ichiro Watanabe, Akira Kikuchi, BLOOD, 116, 21, 469, 470, 2010年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Epidemiological and Genetic Analysis of Sideroblastic Anemia - Multi-center Study In Japan
Rie Ohba, Kazumichi Furuyama, Shigeru Tsuchiya, Atsushi Manabe, Etsuro Ito, Seiji Kojima, Keiya Ozawa, Hideo Harigae, BLOOD, 116, 21, 1716, 1717, 2010年11月, ［査読有り］
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Histopathological review of pediatric bone marrow failures by objective MDS scoring system
M. Ito, A. Hama, A. Manabe, S. Kojima, HISTOPATHOLOGY, 57, 149, 150, 2010年10月
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

9 colorフローサイトメトリーによる小児白血病のマーカー解析
清河 信敬, 恩田 恵子, 高野 邦彦, 藤本 純一郎, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏, Cytometry Research, 20, 2, 27, 33, 2010年09月
白血病細胞株と小児ALL患者の骨髄検体を用いて、市販されている複数の蛍光色素と標識抗体を組み合わせた9カラー・フローサイトメトリーを試み、その実現性と有用性について検討した。その結果、本法は非常に有用性の高い検査手段になりうることが示唆された。1本のチューブで、従来のCD45-gating+2カラー解析の場合の4本分の測定が可能であり、染色過程も含めた検査所要時間が大幅に短縮され、迅速な診断が可能であった。また、使用する検体量も大幅に減量可能であった。, (一社)日本サイトメトリー学会, 日本語

骨髄異形成症候群 (特集 小児白血病・リンパ腫診療のアップデート) -- (病態と治療)
真部 淳, 小児科診療, 73, 8, 1352, 1356, 2010年08月
診断と治療社, 日本語

THE IMPACT OF THE CANCER IN JAPANESE CHILDHOOD CANCER PATIENTS AFTER DISCHARGE FROM MEDICAL TREATMENT
Yuko Takei, Akiko Ogata, Miwa Ozawa, Atsushi Manabe, Hiroshi Moritake, Kei Hirai, Shinichi Suzuki, INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE, 17, 28, 29, 2010年08月
SPRINGER, 英語, 研究発表ペーパー・要旨（国際会議）

小児不応性血球減少症 : 2010年における最新の知見
長谷川 大輔, 真部 淳, 日本小児血液学会雑誌, 24, 3, 161, 167, 2010年06月30日
日本語

乳がん患者とその子どもへのサポートを考える 子どもの行動・情緒的問題　　　　　　　　　　　　　　　
小澤 美和, 伊藤 ゆかり, 阿佐美 百合子, 真部 淳, 山内 英子, 中村 清吾, 日本乳癌学会総会プログラム抄録集, 18回, 656, 656, 2010年05月
(一社)日本乳癌学会, 日本語

診断後早期の臓器障害併発のために臨床試験に参加できなかった重症ALL 7症例の臨床像の検討 : TCCSG L99-15研究
外松 学, 金子 隆, 齋藤 正博, 野口 靖, 高橋 浩之, 矢部 みはる, 真部 淳, 小原 明, 花田 良二, 土田 昌宏, 日本小児血液学会雑誌, 24, 1, 25, 31, 2010年02月28日
日本語

白血病の分子標的療法 (ミニ特集 白血病)
真部 淳, 小児科臨床, 63, 1, 27, 33, 2010年01月
日本小児医事出版社, 日本語

6.多発性骨浸潤により発症したバーキット・リンパ腫の一例(III,2009年度関東甲信越地区小児がん登録研究会)
斎藤 怜, 笠井 恵美, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 真部 淳, 細谷 亮太, 小児がん : 小児悪性腫瘍研究会記録, 47, 3, 478, 478, 2010年
がんの子供を守る会, 日本語

特発性造血障害に関する調査研究 小児の骨髄不全と骨髄異形成症候群に関する研究
中畑龍俊, 真部淳, 特発性造血障害に関する調査研究 平成21年度 総括・分担研究報告書, 38, 39, 2010年
日本語

C-Cbl but Not TET2 Mutations Are Present in Patients with Juvenile Myelomonocytic Leukemia
Hideki Muramatsu, Hideki Makishima, Anna Malgorzata Jankowska, Heather Cazzolli, Christine O'Keefe, Nao Yoshida, Yinyan Xu, Nobuhiro Nishio, Asahito Hama, Hiroshi Yagasaki, Yoshiyuki Takahashi, Koji Kato, Atsushi Manabe, Seiji Kojima, Jaroslaw P. Maciejewski, BLOOD, 114, 22, 174, 175, 2009年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

A COMPREHENSIVE SUPPORT FOR FAMILIES HAVING CHILDREN WITH CANCER
Atsushi Manabe, Miwa Ozawa, Akiko Higuchi, Hiroko Kondo, Motohiro Matoba, Makiko Oshikawa, Shinichi Suzuki, Megumi Oda, Kiyoko Kamibeppu, Keizo Horibe, Ryota Hosoya, PEDIATRIC BLOOD & CANCER, 53, 5, 876, 877, 2009年11月
WILEY-LISS, 英語, 研究発表ペーパー・要旨（国際会議）

東京小児がん研究グループ急性リンパ性白血病治療12から15次研究におけるBCP-ALL-NCI-SR群治療成績の検討　　　　　　　　　　　　　　　
大嶋 宏一, 康 勝好, 小川 千登世, 富澤 大輔, 嶋田 博之, 福島 啓太郎, 藤村 純也, 徳山 美香, 長谷川 大輔, 太田 節雄, 高橋 浩之, 真部 淳, 熊谷 昌明, 菊地 陽, 小原 明, 花田 良二, 土田 昌宏, 小児がん, 46, プログラム・総会号, 226, 226, 2009年11月
(NPO)日本小児がん学会, 日本語

TCCSG-L1602治療研究におけるDay8末梢血-芽球数のフローサイトメトリー測定についての評価　　　　　　　　　　　　　　　
恩田 恵子, 平林 真介, 清河 信敬, 齊藤 正博, 森 鉄也, 福島 敬, 藤本 純一郎, 真部 淳, 康 勝好, 熊谷 昌明, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏, 小児がん, 46, プログラム・総会号, 228, 228, 2009年11月
(NPO)日本小児がん学会, 日本語

東京小児がん研究グループにて1981年から1999年の5つの研究に登録された小児急性リンパ性白血病2035例の長期追跡結果　　　　　　　　　　　　　　　
土田 昌宏, 小原 明, 花田 良二, 真部 淳, 熊谷 昌明, 高橋 浩之, 金沢 崇, 藤村 純也, 富澤 大輔, 康 勝好, 嶋田 博之, 森 鉄也, 後藤 裕明, 福島 敬, 小池 和俊, 野口 靖, 小川 千登世, 犬飼 岳史, 福島 啓太郎, 塩原 正明, 加藤 陽子, 前田 美穂, 菊地 陽, 梶原 道子, 矢部 晋正, 外松 学, 太田 節雄, 磯山 恵一, 金子 隆, 林 泰秀, 東京小児がん研究グループALL委員会, 臨床血液, 50, 9, 904, 904, 2009年09月
(一社)日本血液学会-東京事務局, 日本語

小児B細胞性リンパ腫のマイクロアレイを用いたmolecular karyotypingと網羅的発現遺伝子解析　　　　　　　　　　　　　　　
清河 信敬, 恩田 恵子, 飯島 一智, 長谷川 大輔, 加藤 元博, 大喜多 肇, 齋藤 正博, 森 鉄也, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏, 中川 温子, 小川 誠司, 藤本 純一郎, 臨床血液, 50, 9, 1268, 1268, 2009年09月
(一社)日本血液学会-東京事務局, 日本語

早期強化療法中に肝中心静脈閉塞症を発症した急性リンパ性白血病の1例
吉田 健一, 長谷川 大輔, 中島 健太郎, 有馬 慶太郎, 平林 真介, 小川 千登世, 真部 淳, 細谷 亮太, 日本小児血液学会雑誌, 23, 4, 251, 255, 2009年08月31日
日本語

思春期・若年成人の急性リンパ性白血病に対する治療
真部 淳, 血液・腫瘍科, 59, 1, 88, 92, 2009年07月
科学評論社, 日本語

TCCSG-L1602治療研究/Day8末梢血 芽球数のフローサイトメトリー測定　　　　　　　　　　　　　　　
恩田 恵子, 清河 信敬, 齋藤 正博, 森 鉄也, 藤本 純一郎, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏, Cytometry Research, 19, 抄録集, 57, 57, 2009年06月
(一社)日本サイトメトリー学会, 日本語

MYELODYSPLASTIC SYNDROME AND MYELOPROLIFERATIVE DISEASE IN CHILDREN: A PROSPECTIVE REGISTRATION OF 222 CASES
A. Manabe, S. Hirabayashi, S. Watanabe, Y. Zaike, M. Tsuchida, A. Masunaga, A. Yoshimi, M. Ito, A. Kikuchi, K. Tsuji, A. Ohara, S. Kojima, T. Nakahara, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 94, S1, S1, 2009年04月
FERRATA STORTI FOUNDATION, 英語, 研究発表ペーパー・要旨（国際会議）

A JAPANESE PEDIGREE WITH RUNX1 MUTATION RESULTING IN FAMILIAL PLATELET DISORDER WITH PROPENSITY TO ACUTE MYELOGENOUS LEUKEMIA
D. Hasegawa, C. Ogawa, S. Hirabayashi, M. Park, Y. Hayashi, A. Manabe, R. Hosoya, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 94, S24, S24, 2009年04月
FERRATA STORTI FOUNDATION, 英語, 研究発表ペーパー・要旨（国際会議）

CONGENITAL MYELOPROLIFERATIVE DISEASE WITH GATA-1 MUTATION IN A PHENOTYPICALLY NORMAL INFANT
S. Hirabayashi, K. Arima, T. Kamiya, D. Hasegawa, C. Ogawa, A. Manabe, R. Hosoya, E. Ito, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 94, S29, S29, 2009年04月
FERRATA STORTI FOUNDATION, 英語, 研究発表ペーパー・要旨（国際会議）

IMPACT OF GM-CSF SIGNALING PATHWAY-RELATED GENES ON CLINICAL OUTCOME OF CHILDREN WITH JUVENILE MYELOMONOCYTIC LEUKEMIA
N. Yoshida, H. Yagasaki, Y. Xu, K. Matsuda, A. Yoshimi, Y. Takahashi, K. Matsumoto, K. Kato, J. Ueyama, H. Inada, H. Goto, M. Yabe, K. Kudo, J. Mimaya, A. Kikuchi, K. Koike, A. Manabe, S. Kojima, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 94, S15, S15, 2009年04月
FERRATA STORTI FOUNDATION, 英語, 研究発表ペーパー・要旨（国際会議）

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH FLUDARABINE-CONTAINING REGIMEN IN CHILDREN WITH JUVENILE MYELOMONOCYTIC LEUKEMIA
N. Yabe, A. Manabe, Y. Ohtsuka, K. Watanabe, M. Imamura, M. Kaneda, R. Miyachi, J. Inagaki, Y. Ebihara, N. Yoshida, K. Sakashita, K. Horibe, M. Tsurusawa, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 94, S26, S27, 2009年04月
FERRATA STORTI FOUNDATION, 英語, 研究発表ペーパー・要旨（国際会議）

骨髄異形成症候群の中央診断 : 445例の追跡調査
平林 真介, 真部 淳, 日本小児血液学会雑誌, 23, 1, 53, 57, 2009年02月28日
日本語

小児がんに対するWT1ペプチドによるワクチン療法
澤田 明久, 井上 雅美, 近藤 統, 木本 富子, 山田 佳世, 中山 雅弘, 桑江 優子, 西川 正則, 大川 洋二, 井田 孔明, 徳田 桐子, 真部 淳, 土屋 邦彦, 奥山 宏臣, 窪田 昭男, 川原 央好, 長谷川 利路, 米田 光宏, 竹本 理, 山田 淳二, 川端 秀彦, 田村 太資, 木内 恵子, 平野 慎也, 宇野 誠, 竹下 泰史, 石原 卓, 岡村 隆行, 坂田 尚己, 水谷 修紀, 中畑 龍俊, 迫 正廣, 多和 昭雄, 尾路 祐介, 坪井 昭博, 小山 真穂, 岡 芳弘, 安井 昌博, 杉山 治夫, 河 敬世, 小児がん : 小児悪性腫瘍研究会記録 = Pediatric oncology, 46, 1, 6, 16, 2009年02月25日
手術や放射線,化学療法,造血幹細胞移植などの従来法では根治が期待できない小児白血病,悪性固形腫瘍に対し,WT1ペプチド接種による免疫療法の安全性と有効性を検討した.対象は15例16コース.副作用は局所反応のみで,腫瘍残存例11コース中,臨床的効果を3例に,寛解を1例に認めた.腫瘍量が多いと臨床的効果が得難く,微少腫瘍量で開始できるように,難治例・再発例では治療早期から準備を進める必要がある., がんの子供を守る会, 日本語

骨髄異形成症候群(MDS)--不応性血球減少の観点から (特集 臨床に役立つ貧血治療の実際)
長谷川 大輔, 真部 淳, 小児科診療, 72, 2, 345, 354, 2009年02月
診断と治療社, 日本語

1.膀胱Rhabdoid tumorの女児例(2008年度関東甲信越地区小児がん登録研究会)
比嘉 千明, 中島 健太郎, 吉田 健一, 平林 真介, 神谷 尚宏, 長谷川 大輔, 小川 千登世, 真部 淳, 細谷 亮太, 中村 晃子, 平林 健, 鈴木 高祐, 小児がん : 小児悪性腫瘍研究会記録, 46, 3, 412, 413, 2009年
がんの子供を守る会, 日本語

特発性造血障害に関する調査研究 小児骨髄異形成症候群に関する研究
中畑龍俊, 真部淳, 特発性造血障害に関する調査研究 平成20年度 総括・分担研究報告書, 41, 42, 2009年
日本語

Clinical Outcome of 640 Children with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005
Maurizio Arica, Martin Schrappe, Stephen Hunger, William L. Carroll, Valentino Conter, Paola Di Lorenzo, Atsushi Manabe, Vaskar Saba, Andre Baruchel, Kim Vettenranta, Masahiro Tsuchida, Yves Benoit, Rob Pieters, Gabriele Escherich, Lewis B. Silverman, Ching-Hon Pui, Maria Grazia Valsecchi, BLOOD, 112, 11, 213, 214, 2008年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Significance of Initial Lumbar Puncture on Day8 of Remission Induction Therapy in Childhood Acute Lymphoblastic Leukemia: The Results from the Tokyo Children's Cancer Study Group L99-15 Protocol
Daisuke Hasegawa, Atsushi Manabe, Akira Ohara, Katsuyoshi Koh, Chitose Ogawa, Ryoji Hanada, Masahiro Tsuchida, BLOOD, 112, 11, 339, 339, 2008年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

B precursor-ALLに対する中枢神経白血病予防治療の変遷と成績 TCCSG ALL L89-12,92-13,95-14,99-15研究　　　　　　　　　　　　　　　
小川 千登世, 小原 明, 真部 淳, 菊地 陽, 康 勝好, 富澤 大輔, 藤村 純也, 井上 裕靖, 角南 勝介, 石井 栄三郎, 塩原 正明, 森 鉄也, 高橋 裕之, 林 泰秀, 花田 良二, 土田 昌宏, 小児がん, 45, プログラム・総会号, 190, 190, 2008年11月
(NPO)日本小児がん学会, 日本語

MDSセントラルレビュー症例の解析　　　　　　　　　　　　　　　
平林 真介, 渡辺 静, 真部 淳, 土田 昌宏, 在家 裕司, 増永 敦子, 菅原 幸子, 吉見 礼美, 伊藤 雅文, 辻 浩一郎, 菊地 陽, 中畑 龍俊, 小児がん, 45, プログラム・総会号, 160, 160, 2008年11月
(NPO)日本小児がん学会, 日本語

20-P2-324 小児急性リンパ性白血病患者におけるex vivoアンモニア上昇値をパラメータとしたL-アスパラギナーゼの効果評価(がん薬物療法(その他),来るべき時代への道を拓く)
渡辺 静, 三宅 久美子, 松本 晴菜, 小川 千登世, 長谷川 大輔, 真部 淳, 木津 純子, 細谷 亮太, 日本医療薬学会年会講演要旨集, 18, 336, 336, 2008年09月01日
日本医療薬学会, 日本語

フィラデルフィア染色体陽性急性リンパ性白血病の治療
真部 淳, 日本小児血液学会雑誌, 22, 4, 306, 311, 2008年08月31日
日本語

Congenital Dyserythropoietic Anemiaの全国調査
多賀 崇, 伊藤 剛, 浅見 恵子, 井上 雅美, 吉益 哲, 菊地 陽, 杉田 憲一, 鈴木 信寛, 真部 淳, 岩崎 史記, 小阪 嘉之, 右田 昌宏, 小原 明, 日本小児血液学会雑誌, 22, 4, 233, 238, 2008年08月
我が国の小児におけるCongenital Dyserythropoietic Anemia(CDA)の全国調査を施行した。全国120施設から回答を得(回答率55%)、12症例を把握した。男女比は6:6、診断時年齢は新生児期〜4歳で、乳児期に診断される症例が多かった。1)家族歴は3例にみられた。CDAのタイプはtype Iが4例、type IIが3例、type IIIが2例、variant typeが3例であった。2)新生児期の異常は8例に認められ、7例が治療を要する黄疸であった。3)12例中10例で赤血球輸血が施行され、調査時点では5例が輸血不要となっていた。輸血不要となった理由は、2例(I型)が自然に、1例(II型)が脾摘後に、1例(亜型)が造血幹細胞移植によるものであった。1例は現在も輸血依存状態で、4例は死亡していた。4)死因は肝硬変が1例、CDA以外の基礎疾患によるものが3例であった。死亡年齢は8ヵ月から15歳であった。, 日本小児血液学会, 日本語

小児MDSの診断と治療 (特集 骨髄異形成症候群の基礎と臨床)
本田 裕子, 真部 淳, 細胞, 40, 6, 234, 237, 2008年06月
ニューサイエンス社, 日本語

標準粒子を用いた小児急性白血病の末梢血残存白血病細胞数絶対値直接算定法　　　　　　　　　　　　　　　
恩田 恵子, 清河 信敬, 藤本 純一郎, 宮川 世志幸, 大喜多 肇, 森 鉄也, 齋藤 正博, 牧本 敦, 真部 淳, 康 勝好, 小原 明, 林 泰秀, 花田 良二, 土田 昌宏, Cytometry Research, 18, Suppl., 69, 69, 2008年06月
(一社)日本サイトメトリー学会, 日本語

GATA1遺伝子変異を有する非 Down 症TAM例
平林 真介, 吉田 健一, 有馬 慶太郎, 中川 真智子, 鶴田 志緒, 長谷川 大輔, 小川 千登世, 真部 淳, 草川 功, 細谷 亮太, 日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology, 18, 1, "S, 133"-"S-134", 2008年06月01日
日本語

Benefit and feasibility of initial lumbar puncture and intrathecal chemotherapy on day 8 of remission induction therapy in children with acute lymphoblastic leukaemia (ALL): the results from the Tokyo Children's Cancer Study Group L99-15 protocol
D. Hasegawa, A. Manabe, A. Ohara, K. Koh, C. Ogawa, R. Hanada, M. Tsuchida, BRITISH JOURNAL OF HAEMATOLOGY, 141, 94, 94, 2008年04月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

The ex vivo production of ammonia predicts biologic activity of L-asparaginase in children with ALL
C. Ogawa, A. Manabe, S. Watanabe, K. Miyake, K. Arima, S. Hirabayahi, D. Hasegawa, T. Inoue, J. Kizu, R. Hosoya, BRITISH JOURNAL OF HAEMATOLOGY, 141, 96, 96, 2008年04月
BLACKWELL PUBLISHING, 英語, 研究発表ペーパー・要旨（国際会議）

L-アスパラギナーゼ治療の最近の進歩と問題点
小川 千登世, 真部 淳, 血液・腫瘍科, 56, 3, 382, 388, 2008年03月
科学評論社, 日本語

小児のprimary myelodysplastic syndromeとjuvenile myelomonocytic leukemiaにおけるAML1 geneの変異　　　　　　　　　　　　　　　
増永 敦子, 巌本 三寿, 門福 強樹, 真部 淳, 宮崎 章, 光谷 俊幸, 中畑 龍俊, 日本病理学会会誌, 97, 1, 356, 356, 2008年03月
(一社)日本病理学会, 日本語

遺伝性骨髄不全症候群の分子病態 : Fanconi貧血, dyskeratosis congenitaを中心に (特集 骨髄不全症をめぐる最近の進歩)
長谷川 大輔, 真部 淳, 血液・腫瘍科, 56, 2, 147, 154, 2008年02月
科学評論社, 日本語

小児MDSのセントラルレビュー 453例の解析　　　　　　　　　　　　　　　
真部 淳, 土田 昌宏, 在家 裕司, 増永 敦子, 菅原 幸子, 吉見 礼美, 伊藤 雅文, 辻 浩一郎, 菊地 陽, 中畑 龍俊, 日本小児科学会雑誌, 112, 2, 234, 234, 2008年02月
(公社)日本小児科学会, 日本語

A novel clinical phenotype with juvenile myelomonocytic leukemia-like features and giant platelets in infancy with Wiskott-Aldrich syndrome
Yashiro Kamachi, Ayami Yoshimi, Nobuhiro Watanabe, Kazushi Tamura, Shuichi Ozono, Atsushi Manabe, Seiji Kojima, CLINICAL IMMUNOLOGY, 127, S61, S62, 2008年
ACADEMIC PRESS INC ELSEVIER SCIENCE, 英語, 研究発表ペーパー・要旨（国際会議）

CHARACTERISTICS OF EPILEPSY IN EIGHT PATIENTS WITH INV DUP (15)
Hiroka Takahashi, Y. Takahashi, K. Imai, Atsushi Manabe, R. Hosoya, M. Ogiwara, Hironao Numabe, A. Nezu, T. Nagai, Y. Toribe, N. Kondo, T. Fujiwara, EPILEPSIA, 49, 250, 250, 2008年
WILEY-BLACKWELL PUBLISHING, INC, 英語, 研究発表ペーパー・要旨（国際会議）

TCCSG ALL L99-15治療研究に登録されたAML1 amplificationを有する急性リンパ性白血病3例の臨床的特徴　　　　　　　　　　　　　　　
徳山 美香, 高橋 浩之, 菊池 陽, 野口 靖, 森 鉄也, 小原 明, 真部 淳, 斎藤 友博, 林 泰秀, 花田 良二, 土田 昌宏, 小児がん, 44, プログラム・総会号, 271, 271, 2007年12月
(NPO)日本小児がん学会, 日本語

RAEB/AML M6症候群18例の検討　　　　　　　　　　　　　　　
本田 裕子, 真部 淳, 土田 昌宏, 在家 裕司, 増永 敦子, 井上 雅美, 小林 良二, 大塚 欣敏, 菊地 陽, 中畑 龍俊, 小児がん, 44, プログラム・総会号, 203, 203, 2007年12月
(NPO)日本小児がん学会, 日本語

小児のMDSの分子異常
長谷川 大輔, 真部 淳, 血液・腫瘍科, 55, 5, 579, 586, 2007年11月
科学評論社, 日本語

Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in children with juvenile myelomonocytic leukemia
Nao Yoshida, Hiroshi Yagasaki, Ayami Yoshimi, Yoshiyuki Takahashi, Yinyan Xu, Makito Tanaka, Nobuhiro Watanabe, Kimikazu Matsumoto, Koji Kato, Junichi Ueyama, Hiroko Inada, Hiroaki Goto, Miharu Yabe, Junichi Mimaya, Akira Kikuchi, Atsushi Manabe, Seiji Kojima, BLOOD, 110, 11, 457A, 457A, 2007年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

30-P1-188 小児がん治療における知能障害の検討(がん薬物療法,社会の期待に応える医療薬学を)
渡辺 静, 阿佐美 百合子, 小川 千登世, 長谷川 大輔, 小澤 美和, 真部 淳, 木津 純子, 井上 忠夫, 細谷 亮太, 日本医療薬学会年会講演要旨集, 17, 324, 324, 2007年09月01日
日本医療薬学会, 日本語

小児MDSのセントラルレビュー 453例の解析　　　　　　　　　　　　　　　
真部 淳, 土田 昌宏, 在家 裕司, 増永 敦子, 菅原 幸子, 吉見 礼美, 伊藤 雅文, 辻 浩一郎, 菊地 陽, 中畑 龍俊, 臨床血液, 48, 9, 986, 986, 2007年09月
(一社)日本血液学会-東京事務局, 日本語

小児の骨髄異形成症候群--最新の知見
本田 裕子, 真部 淳, 小児科, 48, 6, 905, 911, 2007年05月
金原出版, 日本語

7.アスペルガー症候群を持つ脳腫瘍患児へのケアの実際 : 社会性を獲得させるために(一般演題,第13回群馬小児がん研究会抄録)
伊藤 愛, 永瀬 恭子, 中村 かおり, 吉川 久美子, 塚崎 百合子, 小林 明雪子, 小川 千登世, 真部 淳, 細谷 亮太, The KITAKANTO medical journal, 57, 1, 100, 101, 2007年02月01日
北関東医学会, 日本語

特発性造血障害に関する調査研究 小児骨髄異形成症候群に関する研究
中畑龍俊, 真部淳, 小島勢二, 小原明, 特発性造血障害に関する調査研究 平成18年度 総括・分担研究報告書, 37, 40, 2007年
日本語

The significance of complete clearance of peripheral blasts after 7 days of prednisolone in children with acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L99-15.
Katsuyoshi Koh, Akira Ohara, Atsushi Manabe, Kouichiro Ikuta, Ryouji Hanada, Hiromasa Yabe, Akitoshi Kinoshita, Kenichi Koike, Yuri Okimoto, Yasushi Noguchi, Michiko Kajiwara, Hiroyuki Takahashi, Kanji Sugita, Takashi Fukushima, Keiichi Isoyama, Masahiro Saito, Akira Kikuchi, Setsuo Ota, Masaaki Kumagai, Yasuhide Hayashi, Tomohiro Saito, Masahiro Tsuchida, BLOOD, 108, 11, 210B, 210B, 2006年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Prognostic factors for relapsed childhood acute lymphoblastic leukemia (ALL): A report from tokyo children's cancer study group (TCCSG) study L95-14 and L-99-15.
Chitose Ogawa, Akira Ohara, Atsushi Manabe, Katsuyoshi Koh, Takashi Kaneko, Hiroaki Goto, Setsuo Ota, Ryoji Hanada, Masahiro Tsuchida, BLOOD, 108, 11, 534A, 534A, 2006年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

Correlation of clinical features with mutational status in children with juvenile myelomonocytic leukemia.
Nan Yoshida, Hiroshi Yagasaki, Yinyan Xu, Makito Tanaka, Nobuhiro Nishio, Hirokazu Hidaka, Asahito Hama, Yoshiyuki Takahashi, Atsushi Manabe, Seiji Kojima, BLOOD, 108, 11, 760A, 760A, 2006年11月
AMER SOC HEMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

肉眼的血尿で発症した特発性血小板減少性紫斑病の1症例
加藤 格, 真部 淳, 小川 千登世, 森本 克, 細谷 亮太, 日本小児血液学会雑誌, 20, 2, 98, 100, 2006年04月30日
英語

26HO3-5 自己免疫性リンパ増殖症候群の臨床的検討 : 活性化T細胞Fas誘導性細胞死の有無と臨床症状、検査所見の比較(口演「リンパ腫・HLH・他」,第22回日本小児がん学会 第48回日本小児血液学会 第4回日本小児がん看護研究会 同時期開催)
徳山 美香, 小原 明, 石田 也寸志, 脇口 宏, 稲井 郁子, 真部 淳, 野田 幸弘, 杉田 完爾, 斉藤 章治, 久間木 悟, 笹原 洋二, 金兼 弘和, 笠原 善仁, 小泉 晶一, 小児がん : 小児悪性腫瘍研究会記録, 43, 3, 491, 491, 2006年
がんの子供を守る会, 日本語