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Last Updated :2024/07/25

研究者情報

マスター

アカウント（マスター）

  • 氏名

    加畑　馨(カハタ　カオル), カハタ　カオル

所属（マスター）

  • 北海道大学病院　医療・ヘルスサイエンス研究開発機構

所属（マスター）

  • 北海道大学病院　医療・ヘルスサイエンス研究開発機構

独自項目

syllabus

  • 2021, トランスレーショナルリサーチ概論, Introduction to Translational Research, 修士課程, 医学院, 臨床研究、トランスレーショナルリサーチ
  • 2021, トランスレーショナルリサーチ概論, Introduction to Translational Research, 博士後期課程, 医学院, 臨床研究、トランスレーショナルリサーチ
  • 2021, トランスレーショナルリサーチ概論, An Introduction to Translational Research, 学士課程, 医学部, トランスレーショナルリサーチ 臨床研究
  • 2021, 一般教育演習(ﾌﾚｯｼｭﾏﾝｾﾐﾅｰ), Freshman Seminar, 学士課程, 全学教育, がん、生命、固形がん、白血病、薬物療法、外科療法、造血幹細胞移植、遺伝子、免疫

researchmap

プロフィール情報

学位

  • 医学博士（北海道大学）

プロフィール情報

  • 姓

    加畑

  • 名

    馨

  • ID各種

    201501048770754036

業績リスト

研究キーワード

  • Regenerative medicine   Cell therapy   Oncology   Hematology   

論文

  • Preeti Prerna M Vaswani, Masahiro Onozawa, Yuta Hasegawa, Hiroyuki Ohigashi, Takahide Ara, Toshihiro Matsukawa, Atsushi Yasumoto, Souichi Shiratori, Hideki Goto, Masao Nakagawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
    Bone marrow transplantation 2023年09月05日
  • Tomoyasu Jo, Satoshi Yoshihara, Yoshiki Okuyama, Keiko Fujii, Tomoko Henzan, Kaoru Kahata, Rie Yamazaki, Wataru Takeda, Yoshihiro Umezawa, Kentaro Fukushima, Takashi Ashida, Minami Yamada-Fujiwara, Ryo Hanajiri, Noboru Yonetani, Yuma Tada, Yuji Shimura, Hidekazu Nishikii, Norio Shiba, Naoya Mimura, Jun Ando, Takayuki Sato, Yasuhiro Nakashima, Junko Ikemoto, Keita Iwaki, Shin-Ichiro Fujiwara, Masaki Ri, Tokiko Nagamura-Inoue, Ryuji Tanosaki, Yasuyuki Arai
    British journal of haematology 2023年04月25日 
    For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 104 /μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3-24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105 /μL; p = 0.022) or low CD4/CD8 ratios (
  • Hideki Sudo, Takashi Miyakoshi, Yudai Watanabe, Yoichi M Ito, Kaoru Kahata, Khin Khin Tha, Nozomi Yokota, Hiroe Kato, Tomoko Terada, Norimasa Iwasaki, Teruyo Arato, Norihiro Sato, Toshiyuki Isoe
    BMJ open 13 2 e065476  2023年02月02日 
    INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.
  • 安本 篤史, 加畑 馨, 豊嶋 崇徳
    臨床検査 65 12 1310 - 1316 株式会社医学書院 2021年12月15日
  • 安本 篤史, 加畑 馨, 豊嶋 崇徳
    臨床検査 65 12 1310 - 1316 (株)医学書院 2021年12月 
    ＜文献概要＞POINT ●ヒト白血球型抗原(HLA)タイピングはドナーとレシピエントの組織適合性を判断するうえで最も重要な検査である.次世代シーケンシングによる超高解像度HLA遺伝子検査が可能となった.●HLA不適合移植では抗HLA抗体の検出が重要である.ルミネックス(Luminex )法による抗HLA抗体の検出だけでなく,免疫複合体キャプチャー(ICFA)法によるHLA交差適合検査も併せて評価する.●CD34陽性細胞測定法はシングルプラットフォーム法が標準である.●サイトメガロウイルス(CMV)感染症の診断は国際的に定量PCR法が標準である.わが国でもようやく認可された.
  • 加畑 馨
    医学のあゆみ 277 10 850 - 854 医歯薬出版 2021年06月05日 [査読無し][招待有り]
  • Souichi Shiratori, Hiroyuki Ohigashi, Takahide Ara, Atsushi Yasumoto, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
    Annals of Hematology 100 5 1321 - 1328 2021年05月 [査読有り][通常論文]
     
    Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 × 109/L vs 0.06 × 109/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD.
  • Shinpei Harada, Kohei Okada, Shota Yokoyama, Daisuke Hidaka, Eiko Hayase, Masahiro Onozawa, Hideki Goto, Daigo Hashimoto, Kaoru Kahata, Tomoyuki Endo, Takanori Teshima
    [Rinsho ketsueki] The Japanese journal of clinical hematology 62 11 1609 - 1614 2021年 
    A 25-year-old male with a medical history of stress polycythemia was admitted to a previous hospital for leukocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed left-shifted myeloid hyperplasia without increased blasts and normal male karyotype. No mutations of JAK2, V617F, and colony-stimulating factor 3 receptor gene (CSF3R) were detected. Fluorescence in-situ hybridization for BCR-ABL1 and FIP1L1-PDGFRA were negative. Based on these findings, a diagnosis of an unclassifiable myeloproliferative neoplasm was made, and he was started on hydroxyurea treatment. He was referred to our hospital in April 2016 for transfusion dependence. Bone marrow examination performed at our hospital revealed granulocytic dysplasia and CSF3R T618I was detected. After induction therapy, CSF3R T618I became undetectable, and he went on to undergo allogeneic stem cell transplantation in October 2016. He has been in remission for >4 years posttransplantation. CSF3R T618I is one of the genes responsible for chronic neutrophilic leukemia and atypical chronic myeloid leukemia, suggesting its involvement in the pathogenesis of this case.
  • 加畑 馨
    Pharm stage 20 8 42 - 45 技術情報協会 2020年11月 [査読無し][招待有り]
  • Hideki Goto, Daisuke Hidaka, Satoshi Yamamoto, Koji Hayasaka, Rie Michimata, Ikuko Kagawa, Kana Sunagoya, Hiroaki Iijima, Eiko Hayase, Souichi Shiratori, Kohei Okada, Junichi Sugita, Masahiro Onozawa, Daigo Hashimoto, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Chikara Shimizu, Takanori Teshima
    Journal of clinical apheresis 35 5 413 - 419 2020年09月 [査読有り][通常論文]
     
    BACKGROUND: Pegfilgrastim has equivalent efficacy to daily granulocyte colony-stimulating factor (G-CSF) in enhancing neutrophil recovery after chemotherapy, but data on its use for peripheral blood stem cell (PBSC) mobilization are limited. We evaluated the safety and efficacy of CD34+ PBSC mobilization by low-dose (3.6 mg) pegfilgrastim after chemotherapy in patients with malignant lymphoma. STUDY DESIGN AND METHODS: Twenty patients with malignant lymphoma were enrolled in this study. Cytotoxic chemotherapy was started on day 1, and 3.6 mg of pegfilgrastim was subcutaneously administered on day 7. CD34+ cells were counted in the peripheral blood daily from days 11 to 14 using a flow cytometric analysis. RESULTS: In 19 of the 20 patients (95%), the CD34+ cell counts in the peripheral blood exceeded 10 × 106/L, with a mean value of 20.3 on day 11, 38.0 on day 12, 40.3 on day 13, and 40.1 on day 14. Older age was associated with lower maximum CD34+ cell mobilization. The most frequent adverse events associated with pegfilgrastim were back pain, nausea, appetite loss, and lactate dehydrogenase elevation. CONCLUSION: Our data indicated that a single dose of 3.6 mg pegfilgrastim on day 7 after chemotherapy safely and effectively mobilized CD34+ cells.
  • Souichi Shiratori, Hiroyuki Ohigashi, Shuichiro Takahashi, Takahide Ara, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
    Annals of hematology 99 3 591 - 598 2020年03月 [査読有り][通常論文]
     
    Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m2 on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.
  • 加畑 馨
    日本アフェレシス学会雑誌 39 1 24 - 27 (一社)日本アフェレシス学会 2020年02月 [査読無し][招待有り]
     
    Extracorporeal photopheresis(ECP:体外循環式光療法)は、その治療原理や効果から、体外循環式光化学療法や体外循環式光免疫療法とも呼ばれる。ECPの作用機序、実施方法、適応疾患、副作用について概説した。日本では、インライン方式のECPがステロイド抵抗性の難治性慢性移植片対宿主病の治療法として保険承認される見通しである。今後、様々な病態への応用が期待される。
  • Takashi Ikeda, Keita Mori, Koji Kawamura, Takehiko Mori, Shotaro Hagiwara, Yasunori Ueda, Kaoru Kahata, Naoyuki Uchida, Nobuhiro Tsukada, Satoshi Murakami, Masahide Yamamoto, Tsutomu Takahashi, Tatsuo Ichinohe, Makoto Onizuka, Yoshiko Atsuta, Yoshinobu Kanda, Shinichiro Okamoto, Kazutaka Sunami, Hiroyuki Takamatsu
    Hematological oncology 37 5 586 - 594 2019年12月 [査読有り][通常論文]
     
    Allogeneic stem cell transplantation (allo-SCT) offers a clinical option to young patients with multiple myeloma (MM) relapsing/progressing after autologous SCT (ASCT); however, this claim remains debatable. Thus, in this retrospective study, we analyzed 526 patients with MM who underwent SCT for MM relapsing/progressing after the prior ASCT using the registry data of the Japan Society for Hematopoietic Cell Transplantation (2001-2015) and compared overall survival (OS) between allo-SCT (n = 192) and autologous stem cell retransplantation groups (ReASCT; n = 334) based on risk factor points. Significant adverse factors for OS in all patients were (1) male sex, (2) less than partial response to SCT, (3) performance status of 2 to 4, and (4) short duration from the prior ASCT. We scored factor 2 as 1 point, factor 3 as 2 points, and factor 4 as 0, 1, or 2 points for more than 30, 9 to 30, or less than 9 months, respectively. We categorized patients into three risk subgroups based on their total points (0, 1-3, and 4-5 points), indicating the usefulness of this scoring system for prognosis prediction and treatment selection. Subgroup comparison revealed OS after ReASCT to be higher than that after allo-SCT in the intermediate-risk subgroup comprising the largest population (28.2% vs 21.5%, P < .004). We observed no significant advantages of allo-SCT over ReASCT in the low- and high-risk subgroups. These findings suggest that ReASCT is more advantageous than allo-SCT in many patients with MM relapsing/progressing after the prior ASCT. However, long-term survival patients were noted only in the allo-SCT group, and allo-SCT could exhibit clinical efficacy, particularly in the low-risk group. While further examination is warranted, allo-SCT could be a potential tool for a specific population with MM relapsing/progressing after the prior ASCT.
  • 骨髄異形成症候群の理解のために 分類と予後因子のup-to-date
    加畑 馨
    日本検査血液学会雑誌 20 2 308 - 314 (一社)日本検査血液学会 2019年07月 [査読無し][招待有り]
     
    骨髄異形成症候群は異形成と無効造血で定義づけられ、多彩な臨床症状を呈する造血器悪性腫瘍である。現在使用されている診断基準には必須基準、決定的基準、および補助基準が規定されているが、しばしば診断確定には困難を伴う。特に形態学的評価である異形成は、評価者間の差が生まれやすいため、定義に従った記述的、定量的評価を心がけなければならない。また最新の分類をよく理解し病型を決定することにより、予後予測に基づいた層別化と治療方針の決定が可能となる。骨髄異形成症候群の病態の本質は、造血幹細胞レベルの遺伝子変異とそれに由来するクローン造血、さらにクローン進展による白血病への移行であるが、近年遺伝子変異の詳細と分子学的機序の解明が目覚ましい。こうした病態の背景を知ることは、日常診療において重要である。(著者抄録)
  • 渡邊 千秋, 加畑 馨, 早瀬 英子, 伊藤 誠, 上床 貴代, 魚住 諒, 林 泰弘, 秋沢 宏次, 清水 力
    日本輸血細胞治療学会誌 65 3 645 - 645 (一社)日本輸血・細胞治療学会 2019年06月
  • Hidaka D, Hayase E, Shiratori S, Hasegawa Y, Ishio T, Tateno T, Okada K, Goto H, Sugita J, Onozawa M, Nakagawa M, Kahata K, Endo T, Hashimoto D, Teshima T
    Clinical transplantation 32 9 e13361  2018年09月 [査読有り][通常論文]
     
    Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-vs-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo-SCT. Among 213 patients who underwent allo-SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.
  • Junichi Hashiguchi, Masahiro Onozawa, Satoshi Oguri, Shinichi Fujisawa, Masahisa Tsuji, Kohei Okada, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Takeshi Kondo, Chikara Shimizu, Takanori Teshima
    Journal of Molecular Diagnostics 20 4 446 - 454 2018年07月01日 [査読有り][通常論文]
     
    Intragenic deletion of IKZF1 is a recurrent genomic alteration in acute lymphoblastic leukemia. The deletions are mediated by illegitimate variable(diversity)joining recombination via cryptic recombination signal sequences (RSSs). We developed a fluorescence in situ hybridization (FISH) probe set that can detect any type of IKZF1 deletion, including the commonly deleted exon 4 to 7 region. The probe set consists of a designed probe for the commonly deleted region (Cy3 red) and a bacterial artificial chromosomes clone probe for detecting the 3′ flanking region (Spectrum Green). Intact IKZF1 showed a fusion signal, and the deleted allele showed loss of the red signal (0R1G1F). The FISH probes worked correctly for human leukemic cell lines and clinical samples. One case showed an atypical break-apart signal (1R1G1F). Inverse PCR of the case revealed rearrangement of the excised IKZF1 fragment into a legitimate RSS site at Ig κ on chromosome 2, suggesting a pathogenic role of this recombination-activating gene 1/2-mediated event. In this study, we established FISH probe detecting IKZF1 deletion in a quick, quantitative, and cost-effective manner, and the results provided a novel insight into B-cell receptor editing by rearrangement of a cryptic RSS-mediated genomic fragment in acute lymphoblastic leukemia pathology.
  • Hidaka D, Onozawa M, Hashiguchi J, Miyashita N, Kasahara K, Fujisawa S, Hayase E, Okada K, Shiratori S, Goto H, Sugita J, Nakagawa M, Hashimoto D, Kahata K, Endo T, Yamamoto S, Tsutsumi Y, Haseyama Y, Nagashima T, Mori A, Ota S, Sakai H, Ishihara T, Imai K, Miyagishima T, Kakinoki Y, Kurosawa M, Kobayashi H, Iwasaki H, Shimizu C, Kondo T, Teshima T
    Clinical lymphoma, myeloma & leukemia 18 11 e469-e479  2018年07月 [査読有り][通常論文]
     
    BACKGROUND: The prognostic effect of Wilms tumor 1 (WT1) expression at the diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of the present study was to determine the correlations of WT1 expression at the diagnosis of AML with established prognostic alterations. PATIENTS AND METHODS: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, single nucleotide polymorphism (SNP) in the WT1 gene (rs16754), and Fms-like tyrosine kinase receptor-3 internal tandem duplication (FLT3-ITD) mutation were analyzed for all patients. The nucleophosmin 1 (NPM1) mutation and CCAAT/enhancer-binding protein-α (CEBPA) double mutation were analyzed for cytogenetically normal (CN)-AML. The KIT mutation was analyzed for core-binding factor AML. RESULTS: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly greater than that in AML with t(8;21). In cases with CN-AML, FLT3-ITD and NPM1 mutations both correlated with greater expression of WT1, and the CEBPA double mutation was related to lower WT1 expression. The existence of both FLT3-ITD and NPM1 mutations showed synergistically greater expression of WT1 in CN-AML. SNP in the WT1 gene (rs16754) was significantly associated with lower expression of WT1. The WT1 levels were not prognostic factors in the total cohort or any cytogenetic group or stratified by SNP status. CONCLUSION: Because WT1 expression has correlated with known prognostic factors, the prognostic effect of WT1 levels could be misunderstood depending on the distribution of the collaborative mutations in each cohort. We have concluded that the prognostic significance of WT1 at the diagnosis of AML is weak compared with the other established prognostic factors.
  • Shinichiro Okamoto, Takanori Teshima, Mizuha Kosugi-Kanaya, Kaoru Kahata, Naomi Kawashima, Jun Kato, Takehiko Mori, Yukiyasu Ozawa, Koichi Miyamura
    International Journal of Hematology 108 3 1 - 8 2018年06月29日 [査読有り][通常論文]
     
    There are few established therapies for chronic graft-versus-host disease (cGVHD) refractory to first-line treatment with steroids. We evaluated the efficacy and safety of extracorporeal photopheresis (ECP) with a third-generation TC-V device in Japanese patients with cGVHD. Fifteen patients with steroid-resistant or -intolerant cGVHD after allogeneic hematopoietic stem cell transplantation participated in this multicenter open-label study. Extracorporeal photopheresis was conducted on days 1–3, week 1 days 1–2, weeks 2–12 and days 1–2, weeks 16, 20, and 24. The composite primary endpoint consisted of evaluation of response and changes in steroid dose 24 weeks after ECP initiation. Secondary endpoints included response over time, concomitant drug dose, quality of life, and safety. Twelve patients completed scheduled ECP therapy eight (66.7%) showed a response at week 24. In all 15 patients, the mean (± standard deviation) steroid dose decreased 0.115 ± 0.230 mg/kg/day from screening to week 24. Five serious, potentially treatment-related adverse events (heart failure, thrombosis in the device, pneumonia, edema, and wheezing) occurred none were fatal. This study confirmed that ECP using the TC-V device was effective, with an acceptable toxicity profile. Further studies in larger cohorts are clearly warranted to determine its optimal use in Japanese patients with cGVHD.
  • Chika Kawajiri-Manako, Emiko Sakaida, Chikako Ohwada, Toshihiro Miyamoto, Taichi Azuma, Jun Taguchi, Takehiko Mori, Yuichi Hasegawa, Tadakazu Kondo, Toshiaki Yujiri, Makoto Yoshimitsu, Kazunori Imada, Shingo Kurahashi, Kaoru Kahata, Tatsuo Ichinohe, Makoto Hirokawa, Yoshiko Atsuta, Chiaki Nakaseko
    Biology of Blood and Marrow Transplantation 24 6 1180 - 1186 2018年06月01日 [査読有り][通常論文]
     
    POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range,.31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70 median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.
  • Ishio T, Sugita J, Tateno T, Hidaka D, Hayase E, Shiratori S, Okada K, Goto H, Onozawa M, Nakagawa M, Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Teshima T
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 24 10 1990 - 1996 2018年06月 [査読有り][通常論文]
     
    Benign precursors of B lymphocytes, termed hematogones, are observed in the regenerative state of hematopoiesis following chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated that expansion of hematogones correlates with better clinical outcomes after allo-HSCT. We retrospectively analyzed the association between hematogones and clinical outcomes in 309 consecutive patients who underwent allo-HSCT, which is the largest population-based cohort reported so far. The incidence of hematogones was significantly higher in complete remission (CR) patients at the time of transplantation than in non-CR patients, after myeloablative conditioning than after reduced-intensity conditioning, with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis than with cyclosporine-based prophylaxis, and with disease other than malignant lymphoma (all P < .05). Patients with hematogones developed less acute GVHD and infections than did those without them (P < .05). Emergence of hematogones was associated with superior GVHD-free relapse-free survival and lower nonrelapse mortality, and was an independent prognostic factor for overall survival, irrespective of donor sources.
  • Miyashita N, Onozawa M, Hayasaka K, Yamada T, Migita O, Hata K, Okada K, Goto H, Nakagawa M, Hashimoto D, Kahata K, Kondo T, Kunishima S, Teshima T
    Annals of hematology 97 4 629 - 640 2018年04月01日 [査読有り][通常論文]
     
    We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbβ3 was partially activated in a resting status, but platelet expression of αIIbβ3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/β3 (p.T720del)-transfected 293T cells in suspension conditions. Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization of αIIbβ3 were observed in αIIb/β3 (p.T720del)-transfected CHO cells. Such morphological changes were reversed by treatment with an FAK inhibitor. These findings imply spontaneous, but partial, activation of αIIbβ3 followed by phosphorylation of FAK as the initial mechanism of abnormal thrombopoiesis. Internalization and decreased surface expression of αIIbβ3 would contribute to aggregation dysfunction. We reviewed the literature of congenital macrothrombocytopenia associated with heterozygous ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the membrane proximal region of αIIbβ3, which affected the critical interaction between αIIb R995 and β3 D723, resulting in a constitutionally active form of the αIIbβ3 complex. Macrothrombocytopenia caused by a heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal region forms a distinct entity of rare congenital thrombocytopenia.
  • 上床 貴代, 後藤 了一, 渡邊 千秋, 秋沢 宏次, 嶋村 剛, 清水 力, 豊嶋 崇徳, 早瀬 英子, 加畑 馨, 橋本 大吾, 伊藤 誠, 魚住 諒, 林 泰弘, 杉田 純一, 腰塚 靖之
    日本輸血細胞治療学会誌 64 5 641 - 648 一般社団法人 日本輸血・細胞治療学会 2018年 [査読有り][通常論文]
     
    <p>＜背景＞肝移植患者は，凝固障害によりしばしば大量出血をきたし，大量の輸血製剤が必要となる．肝移植時のフィブリノゲン製剤の使用で輸血使用量が減少したとの報告があり<sup>1)</sup>，当院でも2012年より脳死肝移植でのフィブリノゲン製剤の使用を導入した．今回，脳死肝移植でのフィブリノゲン製剤の使用による術中出血量と輸血使用量について検討した．＜対象＞2001年2月から2016年8月の間に当院で脳死肝移植を施行した成人44例を対象とし，フィブリノゲン製剤非投与群25例，投与群19例で術中出血量，輸血使用量の比較検討を行った．また，術中出血量が循環血液量を超えた症例33例（非投与群16例，投与群17例）で同様に検討を行った．＜結果＞全症例での比較では両群で術中出血量，輸血使用量に有意差は認めなかった．循環血液量以上の出血を来した33例でサブ解析を施行したところ，投与群で術中出血量が有意に減少した．輸血使用量は投与群において濃厚血小板の使用量が有意に減少し，赤血球液，新鮮凍結血漿は減少傾向が認められた．＜結論＞脳死肝移植ではフィブリノゲン製剤の使用により大量出血を抑制し，輸血使用量を削減できると考えられた．</p>
  • 伊藤 誠, 高橋 秀一郎, 宮下 直洋, 後藤 秀樹, 小野澤 真弘, 白鳥 聡一, 杉田 純一, 橋本 大吾, 秋沢 宏次, 佐藤 典宏, 豊嶋 崇徳, 早瀬 英子, 渡邊 千秋, 上床 貴代, 魚住 諒, 林 泰弘, 早坂 光司, 茂木 祐子, 加畑 馨
    日本輸血細胞治療学会誌 64 6 742 - 751 一般社団法人 日本輸血・細胞治療学会 2018年 [査読有り][通常論文]
     
    <p><b>背景：</b>Spectra Optia<sup>Ⓡ</sup>は，自動インターフェイス管理システムにより，簡便な操作での末梢血幹細胞採取を可能にした．今回我々は末梢血幹細胞採取において，Spectra Optia<sup>Ⓡ</sup>のMNCモード（MNC群）とCMNCモード（CMNC群）の採取産物のCD34陽性細胞数およびCD34陽性細胞採取効率（採取効率）を後方視的に比較検討した．</p><p><b>対象：</b>2013年8月から2018年2月までに当院で末梢血幹細胞採取を行った233例（自家103例，同種130例）を対象とした．</p><p><b>結果：</b>自家末梢血幹細胞採取における採取産物のCD34陽性細胞数および採取効率は，両群において有意差を認めなかった．同種末梢血幹細胞採取においてMNC群と比較してCMNC群の採取産物のCD34陽性細胞数は有意に高値であり，採取効率も有意に良好であった．同種末梢血幹細胞採取の採取効率に影響する因子として，末梢血血小板数と末梢血ヘモグロビン値が挙げられた．</p><p><b>結語：</b>自家末梢血幹細胞採取においては両群ともに良好な成績であったが，同種末梢血幹細胞採取においては，CMNCモードを用いることでより効率的な採取を行える可能性が示唆された．</p>
  • Yasuyuki Arai, Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Michihiro Hidaka, Naoki Kobayashi, Koji Iwato, Toru Sakura, Makoto Onizuka, Yukiyasu Ozawa, Tetsuya Eto, Mineo Kurokawa, Kaoru Kahata, Naoyuki Uchida, Yoshiko Atsuta, Shuichi Mizuta, Shinichi Kako
    AMERICAN JOURNAL OF HEMATOLOGY 93 1 47 - 57 2018年01月 [査読有り][通常論文]
     
    Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30-40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30-40 mg/kg) (N=376) and CY/TBI (N=1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56-1.00; P=.05) with a corresponding improvement in leukemia-free survival (hazard ratio [HR], 0.76; 95%CI, 0.62-0.93; P=.01), particularly in patients transplanted at CR1 with advanced-risk (positive minimal residual disease, presence of poor-risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56-1.00; P=.05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39-0.88; P=.01). The addition of VP16 did not increase post-transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65-1.18; P=.38). This study is the first to reveal the efficacy of the addition of medium-dose VP16 to CY/TBI in high-risk ALL. To establish new myeloablative conditioning regimens including VP16, a large-scale prospective study is necessary.
  • Kahata K, Dadras MS, Moustakas A
    Cold Spring Harbor perspectives in biology 10 1 2018年01月 [査読無し][招待有り]
  • Nakano K, Iwami D, Yamada T, Morita K, Yasuda K, Shibuya H, Kahata K, Shinohara N, Shimizu C
    Transplantation direct 4 1 e337  2018年01月 [査読有り][通常論文]
     
    Background: Mycophenolic acid (MPA) concentration measured by homogeneous particle-enhanced turbidimetric inhibition immunoassay (PETINA) may be overestimated due to its cross-reactivity with pharmacologically inactive MPA glucuronide (MPAG), as well as other minor metabolites, accumulated with renal function impairment or co-administered cyclosporine A. In contrast, high-performance liquid chromatography (HPLC) is precise because it can exclude the cross-reactivity. In this study, we assumed HPLC values for MPA (HPLC-MPA) as a reference and aimed to develop a formula correcting PETINA values for MPA (PETINA-MPA) to more precisely reflect HPLC-MPA. Methods: MPA trough concentrations were measured both by HPLC-UV and PETINA in 39 samples issued from 39 solid-organ transplant recipients. MPAG concentrations were also measured using HPLC UV assay. We determined the impacts of renal function and coadministered calcineurin inhibitor on concentrations of MPA and MPAG measured by HPLC. Then, we evaluated the difference between PETINA-MPA and HPLC-MPA. Finally, we develop a formula to reflect HPLC-MPA by using multilinear regression analysis. Results: MPAG concentration was negatively correlated with estimated glomerular filtration rate (eGFR) (R2 = 0.376, P < 0.001), although MPA was not correlated with eGFR. There were no significant differences in MPA or MPAG concentrations per dose between the patients who were co-administered tacrolimus versus cyclosporine A. Finally, we developed the formulas to reflect HPLC-MPA:Formula 1: Estimated MPA concentration = 0.048 + 0.798 × PETINA-MPAFormula 2: Estimated MPA concentration = - 0.059 + 0.800 × PETINA-MPA + 0.002 × eGFRHowever, there was no significant improvement in the coefficient of determination with addition of eGFR in the formula, suggesting that HPLC-MPA can be well predicted by only 1 variable, PETINA-MPA. Conclusions: This study developed a formula so that PETINA-MPA can be corrected to more precisely reflect HPLC-MPA.
  • Mutsumi Nishida, Kaoru Kahata, Eiko Hayase, Akio Shigematsu, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Takahito Iwai, Junichi Sugita, Hitoshi Shibuya, Chikara Shimizu, Takanori Teshima
    Biology of Blood and Marrow Transplantation 24 9 1896 - 1900 2018年 [査読有り][通常論文]
     
    Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a well-documented complication after hematopoietic stem cell transplantation (HSCT). Transabdominal ultrasonography (US) enables the visualization of blood flow abnormalities and is therefore useful for the diagnosis of SOS/VOD. We herein prospectively evaluated accuracy of a novel US diagnostic scoring system of SOS/VOD based on US findings. We carried out US in 106 patients on day 14 and when SOS/VOD was suspected after allogeneic HSCT. Among 106 patients, 10 patients (9.4%) were diagnosed as SOS/VOD by Baltimore or Seattle criteria. According to univariate analysis of 17 US findings (US-17 screening), we established a novel scoring system (HokUS-10) consisting of 10 parameters, such as gallbladder wall thickening, ascites, and blood flow signal in the paraumbilical vein. The sensitivity and specificity were 100% and 95.8%, respectively. Diagnostic performance of the HokUS-10 was significantly better than US-17 screening. In 4 of 10 patients US detection of SOS/VOD preceded to clinical diagnosis. The HokUS-10 scoring system is useful in the diagnosis of SOS/VOD however, our results should be validated in other cohorts.
  • Koji Kawamura, Shinichi Kako, Shuichi Mizuta, Ken Ishiyama, Jun Aoki, Shingo Yano, Takahiro Fukuda, Naoyuki Uchida, Yukiyasu Ozawa, Tetsuya Eto, Koji Iwato, Heiwa Kanamori, Kaoru Kahata, Tadakazu Kondo, Masashi Sawa, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 23 12 2079 - 2087 2017年12月 [査読有り][通常論文]
     
    The optimal conditioning regimen for elderly patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) remains unclear. We retrospectively analyzed 1607 patients aged 50 years or older with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome (MDS) who underwent allo-HCT using fludarabine/busulfan (FB) or fludarabine/melphalan (FM) between 2007 and 2014. We compared the clinical outcomes among FB2 (busulfan at 6.4 mg/kg iv, n = 463), FB4 (busulfan at 12.8 mg/kg iv, n = 721), and FM140 (melphalan at 140 mg/m(2), n = 423). The nonrelapse mortality (NRM) rates in the FB4 and FM140 groups were higher than that in the FB2 group (hazard ratio [HR], 1.63 [P<.001]; and HR, 1.71 [P<.001], respectively). Conversely, the relapse rates in the FB4 and FM140 groups were lower than that in the FB2 group (HR, .73 [P=.011]; and HR, .56 [P<.001], respectively). There were no significant differences in overall survival (OS) among the FB2, FB4, and FM140 groups. The 3-year OS in patients with high-risk AML and MDS in the FM140 group (37.0% and 60.2%) were superior to those in the FB2 group (24.4% and 45.5%) and the FB4 group (24.6% and 40.6%) (P=.016 and P=.023), whereas there were no differences in OS in the other patients among the 3 groups. In conclusion, the lower rates of relapse in the FB4 and FM140 groups were largely offset by a worse NRM. However, FM140 might be associated with better OS in patients with high-risk AML and MDS. (C) 2017 American Society for Blood and Marrow Transplantation.
  • Shiratori S, Kosugi-Kanaya M, Hayase E, Okada K, Goto H, Sugita J, Onozawa M, Nakagawa M, Kahata K, Hashimoto D, Endo T, Kondo T, Teshima T
    Transplant immunology 46 21 - 22 2017年11月 [査読有り][通常論文]
  • Yusuke Kudo, Taisei Mikami, Mutsumi Nishida, Kazunori Okada, Sanae Kaga, Nobuo Masauzi, Satomi Omotehara, Hitoshi Shibuya, Kaoru Kahata, Chikara Shimizu
    JOURNAL OF MEDICAL ULTRASONICS 44 4 305 - 314 2017年10月 [査読有り][通常論文]
     
    Flow velocity oscillation rate (FVOR) of the renal interlobar vein has been reported to be decreased in patients with urinary obstruction or diabetic nephropathy, and increased in those with hypertension during pregnancy. To clarify the clinical role of the renal interlobar venous FVOR, we investigated the flow velocity patterns of the renal vessels in patients with hypertension (HT) and/or diabetes (DM). Pulsed-wave Doppler sonography was performed in 34 patients: 15 with HT, 10 with DM, and nine with both HT and DM (HT-DM). Each FVOR of the right and left interlobar veins was closely and positively correlated with the ipsilateral interlobar arterial resistive index (RI), especially in the HT group, but not with the estimated glomerular filtration rate. The right interlobar venous FVOR was decreased in the DM and HT-DM groups compared to the HT group. The renal interlobar venous FVOR is strongly influenced by the arterial RI in HT patients, and is reduced in DM patients without an obvious relationship with diabetic nephropathy. These findings should be noted for the clinical application of renal interlobar venous flow analysis.
  • Yusuke Kudo, Taisei Mikami, Mutsumi Nishida, Kazunori Okada, Sanae Kaga, Nobuo Masauzi, Satomi Omotehara, Hitoshi Shibuya, Kaoru Kahata, Chikara Shimizu
    Journal of Medical Ultrasonics 45 1 197 - 197 2017年10月01日 [査読有り][通常論文]
     
    In the original publication of this paper the legend of Fig. 1 should read as: Fig. 1 Pulsed Doppler flow velocity recordings of the aorta (a), right renal artery (b), right renal interlobar artery (c), inferior vena cava (d), right renal vein (e), and right renal interlobar vein (f). PSV peak systolic velocity, EDV end-diastolic velocity, VMAX maximum velocity, VMIN minimum velocity. The second sentence under the heading “Pulsed-wave Doppler sonography” should read as: Pulsed-wave Doppler sonography was performed under the guide of B-mode or color Doppler imaging with simultaneous electrocardiogram recording (Fig. 1). In the same paragraph the sentence after the first equation should read as: We then measured the maximum velocity (VMAX) and minimum velocity (VMIN) of the inferior vena cava and the right and left renal and renal interlobar veins during inspiration and expiration, respectively, and calculated the mean value for each vein.
  • Takahiro Tateno, Masahiro Onozawa, Junichi Hashiguchi, Takashi Ishio, Sayaka Yuzawa, Satomi Matsuoka, Mizuha Kosugi-Kanaya, Kohei Okada, Souichi Shiratori, Hideki Goto, Taichi Kimura, Junichi Sugita, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Shinya Tanaka, Satoshi Hashino, Takanori Teshima
    TRANSPLANT INFECTIOUS DISEASE 19 4 2017年08月 [査読有り][通常論文]
     
    We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post-mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.
  • Satoshi Kondo, Kazuya Takagi, Mutsumi Nishida, Takahito Iwai, Yusuke Kudo, Kouji Ogawa, Toshiya Kamiyama, Hitoshi Shibuya, Kaoru Kahata, Chikara Shimizu
    IEEE TRANSACTIONS ON MEDICAL IMAGING 36 7 1427 - 1437 2017年07月 [査読有り][通常論文]
     
    This paper proposes an automatic classification method based on machine learning in contrast-enhanced ultrasonography (CEUS) of focal liver lesions using the contrast agent Sonazoid. This method yields spatial and temporal features in the arterial phase, portal phase, and post-vascular phase, as well as max-hold images. The lesions are classified as benign or malignant and again as benign, hepatocellular carcinoma (HCC), or metastatic liver tumor using support vector machines (SVM) with a combination of selected optimal features. Experimental results using 98 subjects indicated that the benign and malignant classification has 94.0% sensitivity, 87.1% specificity, and 91.8% accuracy, and the accuracy of the benign, HCC, and metastatic liver tumor classifications are 84.4%, 87.7%, and 85.7%, respectively. The selected features in the SVM indicate that combining features from the three phases are important for classifying FLLs, especially, for the benign and malignant classifications. The experimental results are consistent with CEUS guidelines for diagnosing FLLs. This research can be considered to be a validation study, that confirms the importance of using features from these phases of the examination in a quantitative manner. In addition, the experimental results indicate that for the benign and malignant classifications, the specificity without the post-vascular phase features is significantly lower than the specificity with the post-vascular phase features. We also conducted an experiment on the operator dependency of setting regions of interest and observed that the intra-operator and inter-operator kappa coefficients were 0.45 and 0.77, respectively.
  • Naohiro Miyashita, Tomoyuki Endo, Masahiro Onozawa, Daigo Hashimoto, Takeshi Kondo, Katsuya Fujimoto, Kaoru Kahata, Junichi Sugita, Hideki Goto, Toshihiro Matsukawa, Satoshi Hashino, Takanori Teshima
    TRANSPLANT INFECTIOUS DISEASE 19 3 2017年06月 [査読有り][通常論文]
     
    Background: Human herpesvirus 6 (HHV-6) encephalitis/myelitis is now a well-known complication after allogeneic stem cell transplantation (allo-HSCT), particularly after cord blood transplantation (CBT). In this study, we evaluated the risk factors of HHV-6 encephalitis/myelitis. Methods: We evaluated 253 patients who received allo-HSCT from 2007 to 2015 at our institute. HHV-6 encephalitis/myelitis was defined as HHV-6 DNA detection in the cerebrospinal fluid or peripheral blood by polymerase chain reaction in the presence of typical manifestations without other concurrent condition that led to the manifestations. Results: HHV-6 encephalitis/myelitis occurred in 11 patients (4.5%) (9 encephalitis, 3.7%; 2 myelitis, 0.8%). Multivariate analysis showed that CBT, mycophenolate mofetil (MMF) for graft-versus-host disease prophylaxis, history of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and engraftment syndrome (ES) were significantly associated with incidence of HHV-6 encephalitis/myelitis (P=.025, P=.017, P=.017, and P=.014, respectively). Conclusion: Although it has been shown that CBT, ES, and history of allo-HSCT are risk factors for HHV-6 encephalitis/myelitis, our study demonstrated MMF is also a risk factor for the disease.
  • M. Kanaya, Y. Hayashi, D. Hashimoto, T. Endo, J. Sugita, H. Ohigashi, J. Hashiguchi, T. Matsukawa, S. Matsuoka, M. Kosugi-Kanaya, H. Goto, M. Onozawa, K. Kahata, K. Fujimoto, T. Kondo, K. Akizawa, H. Shibuya, C. Shimizu, T. Teshima
    BONE MARROW TRANSPLANTATION 52 5 778 - 780 2017年05月 [査読有り][通常論文]
  • 魚住 諒, 加畑 馨, 渡邊 千秋, 伊藤 誠, 上床 貴代, 林 泰弘, 岩見 大基, 渋谷 斉, 清水 力
    日本輸血細胞治療学会誌 63 2 148 - 148 (一社)日本輸血・細胞治療学会 2017年04月
  • Kahata K, Maturi V, Moustakas A
    Cold Spring Harbor perspectives in biology 10 3 2017年03月 [査読有り][通常論文]
     
    Epithelial cells contribute to the development of various vital organs by generating tubular and/or glandular architectures. The fully developed forms of ductal organs depend on processes of branching morphogenesis, whereby frequency, total number, and complexity of the branching tissue define the final architecture in the organ. Some ductal tissues, like the mammary gland during pregnancy and lactation, disintegrate and regenerate through periodic cycles. Differentiation of branched epithelia is driven by antagonistic actions of parallel growth factor systems that mediate epithelial-mesenchymal communication. Transforming growth factor-β (TGF-β) family members and their extracellular antagonists are prominently involved in both normal and disease-associated (e.g., malignant or fibrotic) ductal tissue patterning. Here, we discuss collective knowledge that permeates the roles of TGF-β family members in the control of the ductal tissues in the vertebrate body.
  • 中央診療部門における成人先天性心疾患および小児の心エコーの実施に向けた取り組み
    横山 しのぶ, 山田 聡, 佐々木 理, 岩野 弘幸, 西野 久雄, 井上 真美子, 武田 充人, 西田 睦, 澁谷 斉, 加畑 馨, 清水 力
    日本成人先天性心疾患学会雑誌 6 1 147 - 147 日本成人先天性心疾患学会 2017年01月
  • 中野 恵一, 山田 武宏, 安田 慶子, 山下 直樹, 澁谷 斉, 加畑 馨, 井関 健, 清水 力
    日本臨床検査自動化学会会誌 41 5 659 - 664 (一社)日本臨床検査自動化学会 2016年11月 [査読無し][通常論文]
     
    免疫抑制薬として用いられているミコフェノール酸モフェチルは、消化管で吸収され、加水分解を受けてミコフェノール酸(MPA)に変換される。さらに、MPAは肝臓でグルクロン酸抱合体(MPAG)に代謝され、その大部分が腎臓から排泄される。また、一部は胆汁へ排泄され、腸管循環によりMPAとして再吸収され、血中へ移行する。MPA濃度の測定方法は、従来からHPLC法を原理として測定されてきた。近年では、簡便かつ迅速に測定できる免疫学的測定法(EMIT法やPETINA法)が開発され普及してきているが、免疫学的測定法は代謝産物と交差反応することが報告されている。今回、自験44例のMPAG濃度を測定し、腎機能や併用カルシニューリン阻害剤がMPAGの蓄積にどの程度影響しているか検討するとともに、MPAG蓄積がMPAの血中濃度測定へ及ぼす影響について検討した。結果、MPAG蓄積に対して腎機能とシクロスポリンが有意な影響を及ぼしていることが明らかになり、PETINA法でMPAを測定する際にはこれらの影響を考慮する必要があると考えられた。
  • 伊藤 誠, 加畑 馨, 上床 貴代, 魚住 諒, 林 泰弘, 渡邊 千秋, 澁谷 斉, 後藤 了一, 嶋村 剛, 清水 力
    MHC: Major Histocompatibility Complex 23 2Suppl. 86 - 86 (一社)日本組織適合性学会 2016年10月
  • Yachiyo Kuwatsuka, Junya Kanda, Hirohito Yamazaki, Takehiko Mori, Koichi Miyamura, Shinichi Kako, Naoyuki Uchida, Kazuteru Ohashi, Yukiyasu Ozawa, Yoshiyuki Takahashi, Chiaki Kato, Koji Iwato, Ken Ishiyama, Hikaru Kobayashi, Tetsuya Eto, Kaoru Kahata, Jun Kato, Toshihiro Miyamoto, Koji Kato, Shinicihro Mori, Yoshiko Atsuta, Fumihiko Kimura, Yoshinobu Kanda
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 22 10 1836 - 1843 2016年10月 [査読有り][通常論文]
     
    Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8 matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio pin.55; 95% confidence interval [CI],.32 to.94; P=.029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR,.55; 95% CI,.29 to 1.02) or 6/8-matched UBMT (HR,.67; 95% CI,.32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old, survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. (C) 2016 American Society for Blood and Marrow Transplantation.
  • Shinobu Yokoyama, Hiroyuki Iwano, Satoshi Yamada, Mahito Takeda, Sanae Kaga, Masahiro Nakabachi, Hisao Nishino, Ayako Ichikawa, Ayumu Abe, Kazunori Okada, Daisuke Murai, Taichi Hayashi, Mutsumi Nishida, Hitoshi Shibuya, Kaoru Kahata, Chikara Shimizu, Taisei Mikami, Hiroyuki Tsutsui
    Journal of cardiology cases 14 3 82 - 86 2016年09月 
    Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of thrombi on previously undamaged heart valves in the absence of bacteremia and predominantly affects patients with hypercoagulable state. Although the diagnosis is usually based on transthoracic echocardiography, little is known about the serial changes of the vegetation in response to treatment. We experienced a 42-year-old woman with advanced uterine cancer and asymptomatic cerebral embolization. Plasma d-dimer level was markedly elevated and echocardiography showed highly mobile masses attached to the anterior and posterior mitral leaflets with moderate regurgitation. Based on these findings, she was diagnosed as having NBTE associated with uterine cancer and intravenous administration of heparin and chemotherapy were performed. Follow-up echocardiography revealed the disappearance of the vegetation and reduction of mitral regurgitation. Uterine cancer was successfully treated by surgery and recurrence of the valvular lesion did not occur. .
  • Keiichi Nakano, Keiko Yasuda, Hitoshi Shibuya, Takanori Moriyama, Kaoru Kahata, Chikara Shimizu
    ANNALS OF CLINICAL BIOCHEMISTRY 53 4 511 - 515 2016年07月 [査読有り][通常論文]
     
    We report a case of transient human anti-mouse antibody from a 64-year-old man in a carbohydrate antigen 19-9 immunoassay using an AIA 1800 analyser that generated immune enhancement after surgical resection of recurrent cancer. Methods: The carbohydrate antigen 19-9 concentration was measured using an AIA 1800 analyser and a UniCel Dxl 800. Size-exclusion high-performance liquid chromatography was carried out on a Superose 12 column to estimate the carbohydrate antigen 19-9 elution profile using an AIA 1800 analyser. To determine whether IgM in the patient contributed to the carbohydrate antigen 19-9 immunoassay, immunoprecipitation was performed. Furthermore, mouse immunoglobulins were added to the patient's serum to verify that the patient's IgM reacted with it. Results: The carbohydrate antigen 19-9 concentration was > 400 and 9.5 kU/L using an AIA 1800 analyser and using a UniCel Dxl 800, respectively. In the single carbohydrate antigen 19-9 peak, the molecular weight corresponded to IgM by size-exclusion high-performance liquid chromatography on a Superose 12 column. In the immunoprecipitation reaction and addition of mouse immunoglobulins, there was interference for anti-human IgM and mouse immunoglobulins whose recoveries were 3.2 and 14.2%, respectively. These results indicated that IgM in the patient's serum interfered with the carbohydrate antigen 19-9 immunoassay using an AIA 1800 analyser. Conclusion: A novel transient human anti-mouse antibody generated with immune activation in a carbohydrate antigen 19-9 immunoassay using an AIA 1800 analyser was identified in a patient with rectal cancer after surgical resection. These findings demonstrate the importance of monitoring tumour markers in patients after treatment with mouse monoclonal antibody.
  • Toshihiro Matsukawa, Daigo Hashimoto, Junichi Sugita, Seitarou Nakazawa, Takae Matsushita, Haruhiko Kashiwazaki, Hideki Goto, Masahiro Onozawa, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Yutaka Yamazaki, Takanori Teshima
    INTERNATIONAL JOURNAL OF HEMATOLOGY 104 1 117 - 124 2016年07月 [査読有り][通常論文]
     
    Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT. Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m(2); days +3 and +6: 10 mg/m(2)) with 10-7-7 MTX (day +1: 10 mg/m(2); day +3 and +6: 7 mg/m(2)) in combination with tacrolimus. The cumulative incidence rates of grades II-IV acute GVHD, grades III-IV acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent. The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11-31 days), while that in the 10-7-7 group was 15 days (range, 12-19 days) (P = 0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13-49 days) than that in the 15-10-10 MTX group (27 days; range, 9-405 days) (P = 0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P = 0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD.
  • Mutsumi Nishida, Kaoru Kahata, Akio Shigematsu, Megumi Satoh, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Akihiro Iguchi, Junichi Sugita, Hitoshi Shibuya, Chikara Shimizu, Takanori Teshima
    GASTROENTEROLOGY 150 4 S922 - S922 2016年04月 [査読無し][通常論文]
  • 岩井 孝仁, 西田 睦, 佐藤 恵美, 工藤 悠輔, 表原 里実, 藤田 裕美, 真鍋 徳子, 小松 嘉人, 加畑 馨, 清水 力
    超音波医学 43 1 115 - 122 一般社団法人 日本超音波医学会 2016年 
    症例は70歳代，女性．主訴は心窩部痛．ALT持続正常HCVキャリアで，前医にて経過観察中であった．1年半前の超音波検査（US）で，肝S4に均質的な低エコー域を認めていたが，明らかな腫瘤としては認識されず，同時期のCTでも異常所見は指摘されなかったため経過観察されていた．経過観察中のUSで低エコー域は明瞭化，サイズ増大し明らかな腫瘤性病変として認識された．CTにては肝腫瘤および胃食道接合部に肥厚を認め，胃食道接合部癌と転移性肝癌の疑いで，精査加療目的に当院紹介となった．当院USにて，肝S4を主座とする境界明瞭な最大径91 mmの充実性腫瘤を認めた．辺縁は低エコーで中心部は高エコーを呈していた．肝門部には境界明瞭で低エコーのリンパ節腫大を多数認めた．Sonazoid®造影超音波検査（CEUS）では，動脈相で辺縁から内部に流入する微細点状の造影効果を認め，主に辺縁は強く造影されたが，中心部の造影効果はみられなかった．門脈相で辺縁の造影効果は減弱し，後血管相で造影欠損像を呈した．CTでは，内部に変性ないし壊死を疑う低吸収域を伴う乏血性腫瘤の形態であった．また，肝門部の他，頸部と左腋窩にリンパ節腫大像を認めた．診断目的で肝腫瘍生検が施行され，病理組織学的診断は，びまん性大細胞型B細胞リンパ腫であり，悪性リンパ腫の肝浸潤と診断された．悪性リンパ腫の肝臓病変は，低エコーで均質な性状を呈する腫瘤性病変が多く，中心部が壊死を呈する症例の報告は少ない．今回，CEUSを施行した中心部に変性または壊死を疑う悪性リンパ腫肝浸潤の1症例を経験したので報告する．
  • Erna Raja, Kalliopi Tzavlaki, Robin Vuilleumier, Karolina Edlund, Kaoru Kahata, Agata Zieba, Anita Moren, Yukihide Watanabe, Iryna Voytyuk, Johan Botling, Ola Soderberg, Patrick Micke, George Pyrowolakis, Carl-Henrik Heldin, Aristidis Moustakas
    ONCOTARGET 7 2 1120 - 1143 2016年01月 [査読有り][通常論文]
     
    The protein kinase LKB1 regulates cell metabolism and growth and is implicated in intestinal and lung cancer. Bone morphogenetic protein (BMP) signaling regulates cell differentiation during development and tissue homeostasis. We demonstrate that LKB1 physically interacts with BMP type I receptors and requires Smad7 to promote downregulation of the receptor. Accordingly, LKB1 suppresses BMP-induced osteoblast differentiation and affects BMP signaling in Drosophila wing longitudinal vein morphogenesis. LKB1 protein expression and Smad1 phosphorylation analysis in a cohort of non-small cell lung cancer patients demonstrated a negative correlation predominantly in a subset enriched in adenocarcinomas. Lung cancer patient data analysis indicated strong correlation between LKB1 loss-of-function mutations and high BMP2 expression, and these two events further correlated with expression of a gene subset functionally linked to apoptosis and migration. This new mechanism of BMP receptor regulation by LKB1 has ramifications in physiological organogenesis and disease.
  • 魚住 諒, 岩崎 澄央, 福元 達也, 秋沢 宏次, 渋谷 斉, 加畑 馨, 清水 力
    臨床病理 63 補冊 141 - 141 (一社)日本臨床検査医学会 2015年10月
  • E-Jean Tan, Kaoru Kahata, Oskar Idas, Sylvie Thuault, Carl-Henrik Heldin, Aristidis Moustakas
    NUCLEIC ACIDS RESEARCH 43 1 162 - 178 2015年01月 [査読有り][通常論文]
     
    The loss of the tumour suppressor E-cadherin (Cdh1) is a key event during tumourigenesis and epithelial-mesenchymal transition (EMT). Transforming growth factor-beta (TGF beta) triggers EMT by inducing the expression of non-histone chromatin protein High Mobility Group A2 (HMGA2). We have previously shown that HMGA2, together with Smads, regulate a network of EMT-transcription factors (EMT-TFs) like Snail1, Snail2, ZEB1, ZEB2 and Twist1, most of which are well-known repressors of the Cdh1 gene. In this study, we show that the Cdh1 promoter is hypermethylated and epigenetically silenced in our constitutive EMT cell model, whereby HMGA2 is ectopically expressed in mammary epithelial NMuMG cells and these cells are highly motile and invasive. Furthermore, HMGA2 remodels the chromatin to favour binding of de novo DNA methyltransferase 3A (DNMT3A) to the Cdh1 promoter. E-cadherin expression could be restored after treatment with the DNA de-methylating agent 5-aza-2'-deoxycytidine. Here, we describe a new epigenetic role for HMGA2, which follows the actions that HMGA2 initiates via the EMT-TFs, thus achieving sustained silencing of E-cadherin expression and promoting tumour cell invasion.
  • Paraskevi Heldin, Kaustuv Basu, Berit Olofsson, Helena Porsch, Inna Kozlova, Kaoru Kahata
    JOURNAL OF BIOCHEMISTRY 154 5 395 - 408 2013年11月 [査読有り][通常論文]
     
    Clinical and experimental data indicate that hyaluronan accumulates in breast cancer compared with normal breast epithelium, which correlates to poor prognosis. In this review, we discuss the expression of genes encoding enzymes that synthesize or degrade hyaluronan, i.e. hyaluronan synthases and hyaluronidases or bind hyaluronan, i.e. CD44 and receptor for hyaluronan-mediated motility (RHAMM, also designated as HMMR or CD168), in relation to breast cancer progression. Hyaluronan and hyaluronan receptors have multi-faceted roles in signalling events in breast cancer. A better understanding of the molecular mechanisms underlying these signalling pathways is highly warranted and may lead to improvement of cancer treatment.
  • Satoshi Hashino, Shojiro Takahashi, Rena Morita, Hiroe Kanamori, Masahiro Onozawa, Takahito Kawamura, Kaoru Kahata, Takeshi Kondo, Issei Tokimatsu, Takashi Sugita, Koji Akizawa, Masahiro Asaka
    Blood Research 48 2 154 - 156 2013年 [査読有り][通常論文]
  • Caja L, Kahata K, Moustakas A
    Current pharmaceutical design 18 27 4072 - 4086 2012年09月 [査読有り][通常論文]
     
    The transforming growth factor beta (TGF beta) family embraces many growth factors including the Activins and bone morphogenetic proteins (BMPs). The pathways mediated by these growth factors are implicated in many fundamental biological processes such as early embryonic development, organ morphogenesis and adult tissue homeostasis and in a large number of pathologies including cancer. The action of these pathways is often contextual, which means that different cell types present different physiological responses to these ligands or that the response of one cell type to a certain ligand differs depending on the presence of other signaling proteins that stimulate the target cell together with TGF beta/BMP. The latter usually reflects developmental stage or progression to a specific pathological stage. Not only diverse growth factors and cytokines can influence the response of tissues to TGF beta/BMP, but a single cell type may also show drastically different physiological outcomes to TGF beta or Activin signaling as compared to BMP signaling. This review describes differential physiological outcomes of TGF beta and BMP signaling in normal embryonic or adult stem cells and eventually in cancer stem cells and the process of epithelial-mesenchymal transition. We also summarize evidence on the mechanistic antagonism between TGF beta and BMP signaling as established in vascular differentiation and the progression of tissue fibrosis and cancer. The article ends by discussing possible advantages that the acquired knowledge of these signaling mechanisms offers to new regimes of cancer therapy and the ever-lasting problem of drug resistance elicited by tumor initiating cells.
  • S. Hashino, L. Morita, H. Kanamori, M. Takahata, M. Onozawa, M. Nakagawa, T. Kawamura, F. Fujisawa, K. Kahata, K. Izumiyama, M. Yonezumi, K. Chiba, T. Kondo, M. Asaka
    EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES 31 2 173 - 178 2012年02月 [査読有り][通常論文]
     
    Despite the availability of newer classes of antibiotics, infection with multi-drug-resistant bacteria is a serious problem. To suppress the appearance of multi-drug-resistant bacteria and to avoid severe infection derived from febrile neutropenia (FN), we conducted cycling the administration of antibiotics for FN in patients with hematological malignancy. The treatment protocol consisted of the administration of four antibiotics each for 3 months in 1 year. The above regimen was repeated for 4 years. A total of 193 patients were registered in the protocol. The mean duration of the administration of cycling antibiotics was 5.9 days (range: 1-16 days). The frequency of FN before the study and during the study was unchanged until the third year, but decreased significantly in the fourth year. The frequency of detection of multi-drug-resistant bacteria in the first year was the same as that before the study was started, but dramatically decreased after the second year. Bacteriological treatment success rates were similar in each trimester and each year. The effective rate was not statistically different in each trimester and each year. We conclude that cycling the administration of antibiotics in patients with FN is useful for suppressing the appearance of multi-drug-resistant bacteria and for obtaining excellent clinical efficacy.
  • Kohei Okada, Asumi Higashiyama, Mutsumi Takahata, Masahiro Onozawa, Kaoru Kahata, Sachiko Ando, Junji Tanaka, Satoshi Hashino, Masahiro Imamura
    INTERNAL MEDICINE 51 20 2937 - 2941 2012年 [査読有り][通常論文]
     
    The prognosis of patients who relapse with acute myeloid leukemia (AML) after undergoing stem cell transplantation (SCT) is poor. There exist some treatments for relapsed AML; however, almost all treatments are associated with a high level of regimen-related toxicities (RRTs). The RRT of donor lymphocyte infusion is lower than that of other treatments; however, the efficacy of this treatment in treating patients with relapsed AML is lower than that observed in patients with chronic myelomonocytic leukemia. We herein report a case of relapsed AML after SCT in a 65-year-old man. We performed donor lymphocyte infusion; however, it was not effective. We then administered chemotherapy with cytosine arabinoside and macrophage colony-stimulating factor/granulocyte colony-stimulating factor and complete remission was achieved. Since graft-versus-host disease occurred after the administration of low-dose chemotherapy in this case, we speculated that the chemotherapy induced a graft-versus-leukemia effect.
  • Maria Sideridou, Roubini Zakopoulou, Konstantinos Evangelou, Michalis Liontos, Athanassios Kotsinas, Emmanouil Rampakakis, Sarantis Gagos, Kaoru Kahata, Kristina Grabusic, Kalliopi Gkouskou, Ioannis P. Trougakos, Evangelos Kolettas, Alexandros G. Georgakilas, Sinisa Volarevic, Aristides G. Eliopoulos, Maria Zannis-Hadjopoulos, Aristidis Moustakas, Vassilis G. Gorgoulis
    JOURNAL OF CELL BIOLOGY 195 7 1123 - 1140 2011年12月 [査読有り][通常論文]
     
    E-cadherin (CDH1) loss occurs frequently in carcinogenesis, contributing to invasion and metastasis. We observed that mouse and human epithelial cell lines overexpressing the replication licensing factor Cdc6 underwent phenotypic changes with mesenchymal features and loss of E-cadherin. Analysis in various types of human cancer revealed a strong correlation between increased Cdc6 expression and reduced E-cadherin levels. Prompted by these findings, we discovered that Cdc6 repressed CDH1 transcription by binding to the E-boxes of its promoter, leading to dissociation of the chromosomal insulator CTCF, displacement of the histone variant H2A. Z, and promoter heterochromatinization. Mutational analysis identified the Walker B motif and C-terminal region of Cdc6 as essential for CDH1 transcriptional suppression. Strikingly, CTCF displacement resulted in activation of adjacent origins of replication. These data demonstrate that Cdc6 acts as a molecular switch at the E-cadherin locus, linking transcriptional repression to activation of replication, and provide a telling example of how replication licensing factors could usurp alternative programs to fulfill distinct cellular functions.
  • Iwasaki J, Onozawa M, Takahashi S, Okada K, Takahata M, Shigematsu A, Kahata K, Kondo T, Hashino S, Imamura M, Asaka M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 52 3 124 - 128 「臨床血液」編集部 2011年03月 [査読有り][通常論文]
  • Shigematsu A, Yamamoto S, Sugita J, Kondo T, Onozawa M, Kahata K, Endo T, Shiratori S, Ota S, Yamaguchi K, Wakasa K, Takahata M, Goto H, Ito S, Takemura R, Tanaka J, Hashino S, Nishio M, Koike T, Asaka M, Imamura M
    Transplant infectious disease : an official journal of the Transplantation Society 12 5 412 - 420 2010年10月 [査読有り][通常論文]
     
    Although bacterial infection is a major cause of death even after reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), little is known about the epidemiology and risk factors. The incidence of bacterial infection in 43 patients who received allogeneic bone marrow transplantation (BMT) using a RIC regimen was compared with that in 68 patients who received BMT using a myeloablative conditioning regimen, and risk factors for bacterial infection were identified. Before engraftment, incidences of febrile neutropenia (FN) and documented infections (DI) were significantly decreased in RIC patients (FN: 59.5% vs. 89.6%, P<0.01, DI: 4.8% vs. 17.9%, P<0.01). However, incidence of bacterial infection was significantly increased in RIC patients in the post-engraftment phase (53.8% vs. 11.1%, log-rank, P<0.01). Blood stream was the most frequent focus of infection in both groups. In multivariate analysis, RIC and acute graft-versus-host disease were revealed to be significant risk factors for bacterial infection in this phase. In summary, risk of bacterial infection after engraftment was significantly higher in RIC patients, although infection was decreased before engraftment, and we need to develop a RIC-specific strategy against bacterial infection after RIC SCT.
  • Higashiyama A, Hashino S, Onozawa M, Takahata M, Okada K, Kahata K, Taniguchi N, Nasuhara Y, Kubota K, Fujimoto N, Matsuno Y, Nishimura M, Asaka M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 51 5 353 - 356 「臨床血液」編集部 2010年05月 [査読有り][通常論文]
  • Mutsumi Takahata, Satoshi Hashino, Kohei Okada, Masahiro Onozawa, Kaoru Kahata, Junichi Sugita, Akio Shigematsu, Takeshi Kondo, Satoshi Yamamoto, Tomoyuki Endo, Mitsufumi Nishio, Yoichi M. Ito, Junji Tanaka, Takao Koike, Masahiro Asaka, Masahiro Imamura
    AMERICAN JOURNAL OF HEMATOLOGY 85 4 243 - 248 2010年04月 [査読有り][通常論文]
     
    Reduced intensity conditioning (RIC) regimens are widely used in allogeneic stem cell transplantation (SCT). In this study, we retrospectively investigated the clinical outcomes of RIC with fludarabine (Flu; 180 mg/m(2)), intravenous busulfan (BU; 6.4 mg/kg) or oral BU (8 mg/kg), and low-dose total body irradiation (TBI; 4 Gy) (Flu-BU2-TBI) in 66 patients (median age: 54.5 years) with various hematological malignancies. Thirty-eight patients (58%) were high-risk patients (median age: 56 years). The overall survival rate at 2 years of the high-risk patients was 64.5%, which was comparable to the survival rate of 70.9% in standard-risk patients (P = 0.68). The relapse rates at 2 years in the standard-risk and high-risk patients were 16 and 28%, respectively, and day 100 treatment-related mortality rates were 0 and 6%, respectively. The Flu-BU2-TBI regimen for high-risk patients showed therapeutic effects equivalent to those for standard-risk patients and favorable outcomes compared with those of other previous RIC regimens. Am. J. Hematol. 84:243-248, 2010. (C) 2010 Wiley-Liss, Inc.
  • Takeshi Kondo, Atsushi Yasumoto, Kotaro Arita, Jun-ichi Sugita, Akio Shigematsu, Kohei Okada, Mutsumi Takahata, Masahiro Onozawa, Kaoru Kahata, Yukari Takeda, Masato Obara, Satoshi Yamamoto, Tomoyuki Endo, Mitsufumi Nishio, Norihiro Sato, Junji Tanaka, Satoshi Hashino, Takao Koike, Masahiro Asaka, Masahiro Imamura
    INTERNATIONAL JOURNAL OF HEMATOLOGY 91 2 310 - 321 2010年03月 [査読有り][通常論文]
     
    Acute myelogenous leukemia (AML) with favorable cytogenetics responds well to chemotherapy. If the leukemia relapses, allogenic hematopoietic stem transplantation (allo-HSCT) is considered as a treatment option. Since the efficacy of reduced-intensity stem cell transplantation (RIST) for AML with favorable cytogenetics has not been established, we retrospectively analyzed the outcomes of allo-HSCT in AML patients according to cytogenetic risks. The outcome of allo-HSCT for AML patients with favorable cytogenetics seemed to be superior to that for AML patients with intermediate cytogenetics. In AML patients with favorable cytogenetics, the 3-year overall survival (OS) and relapse-free survival (RFS) rates were 88 and 76%, respectively, in the RIST group. Both the 3-year OS and RFS rates were 81% in the conventional stem cell transplantation (CST) group. The outcome of RIST for AML patients with favorable cytogenetics was comparable to that for patients who received CST despite the more advanced age and greater organ dysfunction in RIST group than in CST group. None of the patients died within 90 days after RIST. Moreover, there was no relapse in patients with favorable cytogenetics who were in hematological remission prior to RIST. Thus, RIST for AML patients with favorable cytogenetics in remission is safe and effective.
  • Mukaiyama Y, Hashino S, Onozawa M, Okada K, Takahata M, Kahata K, Asaka M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 50 12 1706 - 1710 「臨床血液」編集部 2009年12月 [査読有り][通常論文]
  • MORITA R, HASHINO S, OKADA K, TAKAHATA M, ONOZAWA M, KAHATA K, KONDO T, IMAMURA M, ASAKA M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 50 11 1655 - 1657 2009年11月 [査読有り][通常論文]
     
    A 53-year-old woman had demonstrated idiopathic thrombocytopenic purpura (ITP) and iron deficiency anemia (IDA) since 1978. Although she was treated with prednisolone for ITP and oral iron compounds for IDA, neither ITP nor IDA showed any improvement. Since her (13)C-urea breath test was positive, Helicobacter pylori (H. pylori) eradication therapy was performed in 2001. The therapy was effective for IDA but not for ITP. Analysis of cases such as this will be useful for clarifying the mechanisms underlying the development of ITP and IDA associated with H. pylori.
  • K. O. Kohei, S. Ando, S. Hasino, H. Huse, R. Morita, M. Takahata, M. Onozawa, K. Kahata, T. Kondo, S. Ota, T. Kawamura, M. Kurosawa, K. Aikawa, T. Ogawa, S. Suzuki, S. Takahashi, K. Izumiyama, H. Iwasaki, M. Maemori, H. Sakai, M. Asaka
    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL 94 619 - 620 2009年06月 [査読無し][通常論文]
  • Akio Shigematsu, Atsushi Yasumoto, Satoshi Yamamoto, Junichi Sugita, Takeshi Kondo, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Shuichi Ota, Norihiro Sato, Mutsumi Takahata, Kohei Okada, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Takao Koike, Masahiro Asaka, Masahiro Imamura
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15 6 679 - 685 2009年06月 [査読有り][通常論文]
     
    Cytomegalovirus (CMV) infection is I of the major causes of morbidity in patients undergoing allogeneic stem cell transplantation (allo-SCT). The incidences of CMV antigenemia and CMV disease in 43 patients who received allogeneic bone marrow trans plantation (BMT) using a reduced-intensity conditioning (RIC) regimen, which mainly consisted of fluclarabine (Flu), busulfan (Bu), and total body irradiation (TBI), were compared with those in 68 patients who received a myeloablative conditioning (MAC) regimen, and risk factors for CMV antigenemia and CMV disease were identified. Before engraftment, grade 3-4 mucosal injury because of the conditioning regimen was significantly decreased in RIC patients (stomatitis: P=.02; diarrhea: P<.01). Rate of engraftment, incidences of acute graft-versus-host disease (aGVHD), and rate of corticosteroid administration were not different in RIC patients and MAC patients. Although the incidences of CMV antigenemia were not significantly different in RIC patients and MAC patients (64.1% versus 57.8%, log rank, P=.59), the incidence of CMV disease was significantly decreased in RIC patients (5.4% versus 20.3%, log rank, P=.04). CMV seropositivity in the patients (P<.01) and corticosteroid administration (P<.01) were revealed by multivariate analysis to be significant risk factors for CMV antigenemia. Grade II-IV aGVHD (P=.02) and grade 3-4 diarrhea before engraftment (P=.04) were revealed to be risk factors for CMV disease. The present study is the first study to show that severe diarrhea before engraftment is a significant risk factor for CMV disease. In summary, risk of CMV disease was significantly decreased in patients without severe mucosal injury of the gut because of the conditioning regimen before engraftment. Biol Blood Marrow Transplant 15: 679-685 (2009) (C) 2009 American Society for Blood and Marrow Transplantation
  • Okada K, Hashino S, Takahata M, Onozawa M, Kahata K, Kondo T, Imamura M, Asaka M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 50 5 419 - 423 一般社団法人 日本血液学会 2009年05月 [査読有り][通常論文]
     
    症例は30歳代，男性で，1997年発症の重症再生不良性貧血である。前医でmPSLパルス療法，ATG, cyclosporineで治療が行われたが，寛解・再燃を繰り返し，徐々に治療耐性となったため，同種骨髄移植目的に当院へ転院となった。移植前精査で，無症候性胆嚢胆石・総胆管結石を認めたが，白血球が低値であることから移植後に結石除去を行う方針とした。転院後，発熱を認め，G-CSFを連日投与しても好中球100/μl以下であり発熱性好中球減少症の状態であった。抗生剤投与により解熱後，骨髄非破壊的前処置でHLA一致ドナーより，非血縁者間同種骨髄移植を行った。移植後day 9に総胆管結石に伴う閉塞性胆管炎を発症した。無菌解除の上，内視鏡的にEBDチューブを挿入し，その後胆管炎症状は軽快した。day 24に骨髄生着し，血小板回復後のday 57にESTを施行し，総胆管結石の排石を行った。
    本症例は生着前の時期に閉塞性胆管炎を発症したが，内科的治療（EBD, 抗生剤投与）により救命しえた。移植前の無症候性胆道結石の扱いについて，定まった方針はなく，その適応に関しては，今後の症例の蓄積とさらなる検討が必要と考えられた。しかし一方で本症例により，たとえ移植前に手術や処置ができなくても，内科的治療により感染を乗り切ることができる可能性も示唆された。
  • R. Morita, S. Hashino, K. Kubota, M. Onozawa, K. Kahata, T. Kondo, S. Suzuki, Y. Matsuno, M. Imamura, M. Asaka
    BONE MARROW TRANSPLANTATION 43 6 507 - 508 2009年03月 [査読無し][通常論文]
  • Onozawa M, Takahashi S, Kanamori H, Kahata K, Kondo T, Hashino S, Asaka M
    Internal medicine journal 39 1 65 - 66 2009年01月 [査読有り][通常論文]
  • 薬剤性過敏症症候群類似の経過を辿った低ガンマグロブリン血症
    白井 慎一, 橋野 聡, 守田 玲菜, 小野澤 真弘, 川村 孝仁, 加畑 馨, 近藤 健, 今村 雅寛, 浅香 正博
    臨床血液 50 1 23 - 28 (一社)日本血液学会-東京事務局 2009年01月 [査読無し][通常論文]
     
    30歳男性。患者は上腹部痛および黒色便が出現し近医を受診、十二指腸潰瘍を認め入院後、肝機能障害と発熱、上半身に紅斑が出現し、肝生検で巨細胞性肝炎の所見からウイルス性肝炎を疑い、天然型インターフェロンα投与が行なわれた。その結果、皮疹は軽快したものの、リンパ球の減少をはじめガンマグロブリン低値、異型リンパ球出現、敗血症を認めたため、著者らの施設へ紹介入院となった。所見では発熱と多数の表在リンパ節腫脹がみられたが、3日目以降、解熱となり、リンパ節腫脹も縮小傾向となった。一方、FDG-PETを行なったところ、両側鼠径、脇窩リンパ節に集積が認められ、入院時の可溶性IL-2レセプター高値から悪性リンパ腫と考えたが、左鼠径リンパ節生検でDermatopathic lymphoadenopathyと診断された。病態が薬剤性過敏症症候群と類似していたためヒトヘルペスウイルス(HHV)-6型の抗体価測定を行なったところ、前医で160倍であったHHV-6 IgGは2560倍に上昇していた。以後、患者は症状が軽減し、退院となった。
  • Shirai S, Hashino S, Morita R, Onozawa M, Kawamura T, Kahata K, Kondo T, Imamura M, Asaka M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 50 1 23 - 28 2009年01月 [査読有り][通常論文]
     
    A 30-year-old man consulted a local hospital because of upper abdominal pain and tarry stool and was admitted because of duodenal ulcer and hepatic dysfunction. On the fifth hospital day, he developed fever and erythema on the upper body. Liver biopsy demonstrated giant cell hepatitis, and interferon alpha was therefore administered. Liver function improved, though total bilirubin increased to 22.3 mg/dl. The eruption and fever improved in the 3rd hospital week, deteriorated again in the 5th hospital week, and then improved again in the 8th hospital week. Thereafter, he was transferred to our hospital for detailed examination of atypical lymphocytosis, lymphopenia, and hypogammaglobulinemia. Many lymph nodes measuring about 1 cm were detected by palpation. After admission to our hospital, lymphoadenopathy and fever improved. We measured the level of HHV-6 antibody since the clinical course was similar to that of drug-induced hypersensitivity syndrome (DIHS). HHV-6 IgG was x2,560, although it had been x160 at the previous hospital. The clinical course appeared similar to that of DIHS, but drugs known to cause DIHS had not been administered.
  • Masahiro Onozawa, Satoshi Hashino, Stephanie Darmanin, Kohei Okada, Rena Morita, Mutsumi Takahata, Akio Shigematsu, Kaoru Kahata, Takeshi Kondo, Junji Tanaka, Masahiro Imamura, Masahiro Asaka
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 14 11 1226 - 1230 2008年11月 [査読有り][通常論文]
     
    Hepatitis B virus (HBV)-reverse seroconversion (RS) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a frequent late-onset complication in recipients with previous HBV infection. We followed 38 allo-HSCT recipients with previous HBV infection, and conducted posttransplant HB vaccine intervention in 13 recipients. First, we followed the recipients without any intervention (historic control) until 2003; hence, we commenced HB vaccination. Out of the patients who underwent transplantation after 2003, 13 recipients were immunized by a standard three-dose regimen after immunosuppressant cessation (vaccine group), whereas 12 recipients were observed without any intervention (nonvaccine group). Eight of the 13 historic control group recipients and 3 of the 12 nonvaccine group recipients, but none of the 13 vaccine group recipients, suffered HBV-RS. Cumulative risks of HBV-RS at 3 years post-HSCT in the historic control, nonvaccine and vaccine groups were 41%, 39%, and 0% respectively (P = .022). We therefore conclude that intervention with HB vaccines is significantly effective in preventing post-HSCT HBV-RS.
  • Rena Morita, Satoshi Hashino, Shinichi Shirai, Noriaki Fujita, Masahiro Onozawa, Kaoru Kahata, Takeshi Kondo, Masahiro Imamura, Masahiro Asaka
    INTERNATIONAL JOURNAL OF HEMATOLOGY 88 2 248 - 250 2008年09月 [査読有り][通常論文]
  • Hashino S, Morioka M, Irie T, Shiroshita N, Kawamura T, Suzuki S, Iwasaki H, Umehara S, Kakinoki Y, Kurosawa M, Kahata K, Izumiyama K, Kobayashi H, Onozawa M, Takahata M, Fujisawa F, Kondo T, Asaka M
    International journal of laboratory hematology 30 4 292 - 299 2008年08月 [査読有り][通常論文]
  • Souichi Shiratori, Atsushi Yasumoto, Junji Tanaka, Akio Shigematsu, Satoshi Yamamoto, Mitsufumi Nishio, Satoshi Hashino, Rena Morita, Mutsumi Takahata, Masahiro Onozawa, Kaoru Kahata, Takeshi Kondo, Shuichi Ota, Kentaro Wakasa, Junichi Sugita, Takao Koike, Masahiro Asaka, Masaharu Kasai, Masahiro Imamura
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 14 7 817 - 823 2008年07月 [査読有り][通常論文]
     
    Adult T cell leukemia/lymphoma (ATL) is a highly aggressive T cell malignancy, and has a poor prognosis. Recently, allogeneic-hematopoietic stem cell transplantation (allo-HSCT) has been suggested to improve the outcome. We retrospectively analyzed 15 patients with ATL who had received allo-HSCT in 2 institutions in Hokkaido, Japan. The median age of the patients was 57 years. The estimated 3-year overall survival (OS) and progression-free survival (PFS) rates were 73.3% and 66.7%, respectively. Calcineurin inhibitor dosage was reduced and administration was discontinued abruptly in 6 of the 15 patients for disease control; as a result, 4 (66.7%) of the 6 patients achieved complete response (CR) or partial response. Therefore, a graft-versus-leukemia/lymphoma (GVL) effect might be induced by discontinuation of immunosuppression. Thirteen of the 15 patients were followed up by monitoring HTLV-1 proviral DNA levels. In 10 of the 11 patients with positive HTLV-1 proviral DNA before allo-HSCT, HTLV-1 proviral DNA became undetectable at least once after allo-HSCT, and only 1 of the 5 patients in whom HTLV-1 proviral DNA became detectable after allo-HSCT relapsed. Compared to the results of past studies, these results show that allo-HSCT greatly improved the prognosis of ATL and suggest a contribution of the induction of a GVL effect. (C) 2008 American Society for Blood and Marrow Transplantation.
  • M. Onozawa, S. Hashino, R. Morita, K. Kahata, T. Kondo, J. Tanaka, M. Imamura, M. Asaka
    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL 93 182 - 182 2008年06月 [査読無し][通常論文]
  • Akio Shigematsu, Takeshi Kondo, Satoshi Yamamoto, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Soichi Shiratori, Shuichi Ota, Masato Ohara, Kentaro Wakasa, Mutsumi Takahata, Yukari Takeda, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Takao Koike, Masahiro Asaka, Masahiro Imamura
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 14 5 568 - 575 2008年05月 [査読有り][通常論文]
     
    We retrospectively evaluated the outcomes of 37 adult patients with acute lymphoblastic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) conditioned with medium-dose VP-16 (VP, 30 mg/kg), cyclophosphamide, (CY, 120 mg/kg), and fractionated total-body irradiation (TBI, 12 Gy) (medium-dose VP/CY/TBI). The median age of the patients was 26 years. Thirteen patients underwent transplantation from HLA-matched related donors (MRD), 18 patients underwent transplantation from HLA-matched unrelated donors (MUD), and 6 patients underwent transplantation from HLA-mismatched donors (MMD). Thirty-two patients received bone marrow and 4 patients received peripheral blood stem cells. Ten patients were Philadelphia chromosome-positive (Ph+) and 35 patients were in complete remission (CR) at transplantation. All of the patients achieved engraftment, and grade 3 organ toxicity before engraftment occurred in 27 patients. Grade H-M acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15 and 18 patients, respectively. No patient developed grade IV acute GVHD (aGVHD) or died of GVHD. At median follow-up of 35.1 months, 32 patients were alive and all Ph+ patients were alive. Three patients died of relapse and 2 died of transplant-related mortality (TRM). The actuarial 3-year overall survival (OS) rate, relapse rate, and TRM rate were 89.2%, 8.1%, and 5.4%, respectively. Non-CR at transplantation, MRD, and no aGVHD were significant adverse prognostic factors for survival. Medium-dose VP/CY/TBI for adult ALL patients was associated with lower relapse rate and no increase in toxicity, resulting in better survival. (C) 2008 American Society for Blood and Marrow Transplantation.
  • Satoshi Hashino, Sumiko Kobayashi, Mutsumi Takahata, Masahiro Onozawa, Masao Nakagawa, Takahito Kawamura, Fumie Fujisawa, Koh Izumiyama, Kaoru Kahata, Takeshi Kondo, Masahiro Asaka
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 13 2 176 - 180 2008年04月 [査読有り][通常論文]
     
    A 27-year-old man with advanced colon cancer that was resistant to conventional chemoradiotherapies was treated with reduced-intensity allogeneic peripheral blood stem cell transplantation (PBSCT). After obtaining complete donor-type chimerism, there was an apparent graft-versus-tumor effect accompanied by severe hepatic graft-versus-host disease (GVHD) showing hyperbilirubinemia, resulting in a stable disease condition that lasted for 18 months, which had not been seen previously in his previous disease history. The antitumor effect observed in this patient was insufficient for the patient to achieve complete remission, because the disease was at an already widespread and treatment-resistant stage. He finally died of hepatic failure due to extensive liver GVHD 65 months after the diagnosis of the advanced colon cancer and 29 months after the allogeneic PBSCT. Prospective studies are necessary to achieve better clinical results in patients with advanced colon cancer.
  • K. Kahata, S. Hashino, L. Morita, M. Onozawa, T. Kondo, M. Imamura, M. Asaka
    BONE MARROW TRANSPLANTATION 41 S209 - S209 2008年03月 [査読無し][通常論文]
  • T. Toubai, D. Hirate, Y. Shono, S. Ota, M. Ibata, S. Mashiko, J. Sugita, A. Shigematsu, Y. Miura, N. Kato, S. Umehara, K. Kahata, Y. Tsutsumi, N. Iwao, N. Toyoshima, J. Tanaka, M. Asaka, M. Imamura
    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY 30 1 75 - 81 2008年02月 [査読有り][通常論文]
     
    A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (> 0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.
  • Morita R, Hashino S, Takahashi S, Kanamori H, Onozawa M, Kahata K, Kondo T, Imamura M, Asaka M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 49 2 89 - 93 2008年02月 [査読有り][通常論文]
     
    We report that granulocyte transfusion (GTX) was effective for prolonged pneumonia at allogeneic bone marrow transplantation. A 58-year-old man with MDS-RAEB-2 was admitted to our hospital for allogeneic bone marrow transplantation. He was complicated with pneumonia, which was not improved with G-CSF and antibiotics. We therefore decided to perform a GTX transplantation. During the period of neutropenia, pneumonia did not deteriorate. A combination of allogeneic stem cell transplantation and GTX is expected not only to improve transplantation results but also to expand the adaptation for transplantation. However, detailed investigation of the effect of GTX in allogeneic stem cell transplantation should be performed, and more cases should be accumulated.
  • Satoshi Hashino, Lena Morita, Mutsumi Takahata, Masahiro Onozawa, Masao Nakagawa, Takahito Kawamura, Fumie Fujisawa, Kaoru Kahata, Koh Izumiyama, Masakatsu Yonezumi, Koji Chiba, Takeshi Kondo, Masahiro Asaka
    INTERNATIONAL JOURNAL OF HEMATOLOGY 87 1 91 - 97 2008年01月 [査読有り][通常論文]
     
    Invasive fungal infection is one of the major causes of death in neutropenic patients undergoing allogeneic stem cell transplantation (SCT). Although prophylactic antifungal therapy with fluconazole (FLCZ) has become the standard care for these patients, there remains a need for more effective and cost-beneficial alternative drugs. We conducted a prospective study to evaluate the usefulness of the administration of micafungin (MCFG) as a prophylactic antifungal therapy for patients undergoing allogeneic SCT. The results were compared with previous data for patients who had received FLCZ. A total of 44 patients who underwent allogeneic SCT were enrolled in the study. Data from 29 patients who received allogeneic SCT using prophylactic FLCZ before this study were used as historical control data. Underlying diseases included acute leukemia (n = 16), non- Hodgkin's lymphoma (n = 11), myelodysplastic syndrome (n = 6), and others (n = 11) in the MCFG group and acute leukemia (n = 18), chronic myelogenous leukemia (n = 6), and others (n = 5) in the FLCZ group. The median durations of administration of MCFG and FLCZ were 36 and 34 days, respectively. Prophylactic success, defined as the absence of proven, probable, and possible invasive fungal infection (IFI) until the end of prophylactic therapy was achieved in 36 (87.8%) of the 41 evaluated patients in the MCFG group and in 65.5% of the patients in the FLCZ group (P = 0.038). No patients in the MCFG group showed proven or probable IFI, whereas proven or probable IFI was observed in three patients in the FLCZ group. Four patients in the MCFG group required dose escalation due to febrile neutropenia. Although one patient in the MCFG group required the discontinuation of MCFG due to allergic skin eruption (grade 2), none of the other patients in either group required dose reduction due to adverse effects. Although the study design was not a prospective randomized trial, our results indicate that the administration of MCFG at a daily dose of 100 mg is promising for prophylactic antifungal therapy in patients undergoing allogeneic SCT.
  • Kahata K, Hashino S, Takahata M, Fujisawa F, Kondo T, Kobayashi S, Fujita Y, Shimizu H, Imamura M, Asaka M
    Acta haematologica 120 1 14 - 18 2008年 [査読有り][通常論文]
     
    A 22-year-old Japanese man was diagnosed with Sezary syndrome with large cell transformation. His skin lesions persisted after treatment with 7 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), psoralen and ultraviolet light A, and total skin electron beam irradiation. He subsequently underwent allogeneic bone marrow transplantation by reduced-intensity conditioning from a human leukocyte antigen-identical unrelated donor. He developed grade II of acute graft-versus-host disease and extensive-type chronic graft-versus-host disease. He has no signs of disease 36 months after the transplantation. The prognosis of patients with advanced stage of mycosis fungoides or Sezary syndrome is very poor. Allogeneic hematopoietic stem cell transplantation, especially by reduced-intensity conditioning, is expected to become a curative treatment option, and graft-versus-tumor effect might play a critical role for sustained remission. Copyright (C) 2008 S. Karger AG, Basel.
  • Takeshi Kondo, Akio Mori, Masahiro Onozawa, Kaoru Kahata, Satoshi Hashino, Junji Tanaka, Masahiro Imamura, Masanobu Morioka, Masahiro Asaka
    BLOOD 110 11 539A - 539A 2007年11月 [査読無し][通常論文]
  • Masahiro Onozawa, Satoshi Hashino, Shojiro Takahashi, Rena Morita, Hiroe Kanamori, Kaoru Kahata, Takeshi Kondo, Masahiro Asaka
    INTERNATIONAL JOURNAL OF HEMATOLOGY 86 4 374 - 376 2007年11月 [査読有り][通常論文]
  • S. Hashino, K. Kahata, M. Onozawa, T. Kondo, H. Kanamori, S. Takahashi, M. Asaka
    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL 92 452 - 452 2007年06月 [査読無し][通常論文]
  • Masao Nakagawa, Satoshi Hashino, Mutsumi Takahata, Takahito Kawamura, Fumie Fujisawa, Kaoru Kahata, Takeshi Kondo, Masahiro Imamura, Sachiko Ando, Masahiro Asaka
    INTERNATIONAL JOURNAL OF HEMATOLOGY 85 5 443 - 445 2007年06月 [査読有り][通常論文]
     
    A 56-year-old woman with a poor-prognosis chronic active Epstein-Barr virus (CAEBV) infection underwent reduced-intensity stem cell transplantation (RIST) using cryopreserved cord blood (CB). Administration of EBV-seronegative CB cells following a reduced-intensity conditioning regimen was effective and well tolerated. Complete remission with no symptoms, low titers of EBV-related antibodies, and an undetectable level of EBV DNA in peripheral blood mononuclear cells continued for 16 months after RIST This report is the first of successful RIST with CB for an adult with CAEBV infection. The results also show that a graft-versus-CAEBV effect can be achieved in an allogeneic hematopoietic stem cell transplantation setting.
  • Masahiro Onozawa, Satoshi Hashino, Mutsumi Takahata, Fumie Fujisawa, Takahito Kawamura, Masao Nakagawa, Kaoru Kahata, Takeshi Kondo, Shuichi Ota, Junji Tanaka, Masahiro Imamura, Masahiro Asaka
    JOURNAL OF CLINICAL MICROBIOLOGY 44 12 4441 - 4443 2006年12月 [査読有り][通常論文]
     
    Reactivation of latent varicella-zoster virus (VZV), presenting as localized zoster or as disseminated infection, is a common and potentially serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence hemagglutination method after HSCT and also studied VZV DNA by real-time PCR during clinical VZV reactivation using cryopreserved serum samples. No significant difference was found between anti-VZV titers in 13 patients with VZV infection (localized zoster in 11 patients and disseminated zoster in 2 patients) and in 13 subjects without VZV infection at each time point after HSCT. Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than those of localized zoster cases (P = 0.10). Serum VZV DNA copy numbers at the onset of disseminated zoster cases tended to be higher than those of localized zoster cases (P = 0.09). A strong inverse correlation was found between preexisting anti-VZV titer and serum VZV DNA at onset (r = -0.90, P = 0.006). In HSCT recipients, preexisting antibody does not prevent the development of VZV reactivation but may contribute to decreased viral load at onset, resulting in a mild clinical course.
  • Masahiro Onozawa, Takeshi Kondo, Hiroe Kanamori, Kaoru Kahata, Satoshi Hashino, Masahiro Asaka
    BLOOD 108 11 545A - 545A 2006年11月 [査読無し][通常論文]
  • Tomomi Toubai, Junji Tanaka, Shuichi Ota, Naoko Kato, Shintaro Umehara, Kaoru Kahata, Nobuyasu Toyoshima, Masahiro Asaka, Masahiro Imamura
    Japanese Journal of Antibiotics 58 6 507 - 517 2005年12月 [査読有り][通常論文]
     
    We have previously reported that itraconazole (ITCZ) at a dose of 200 mg/day is more effective than ITCZ at a dose of 100mg/day and is safe for prophylaxis of mycosis. In this prospective study, 37 patients with hematological malignancies were administered 200 mg/day of ITCZ for prophylaxis of mycosis during neutropenia. Although none of the patients developed mycosis, 31 patients (83.8%) of the ITCZ administered patients developed neutropenia (neutrophil < 1000/μL), and 12 patients of them showed the possibility of fugitive fungal infection. The prolonged neutropenia and low neutrophil level were observed in the patients with malignant lymphoma at stage III-IV, which suggested the necessity of prophylactic antifungal drugs. Four patients showed the adverse events which might be caused by drug interactions between ITCZ and vinca alkaloid. However adequately modified administration of ITCZ prevented these effect. There were no other obvious side effects which were supposed to be caused by prophylactic ITCZ administration. Twenty-eight patients were measured plasma concentration of ITCZ about 10 days after the beginning of administration and mean trough ITCZ level was expected to be above the effective level (250ng/ml). These results suggested that ITCZ is effective and safe for prophylaxis of mycosis during neutropenia in patients with hematological malignancies.
  • T Toubai, J Tanaka, S Ota, A Mori, M Ibata, Y Shono, S Mashiko, J Sugita, Y Miura, N Kato, S Umehara, K Kahata, N Toyoshima, M Asaka, M Imamura
    INTERNAL MEDICINE 44 5 476 - 479 2005年05月 [査読有り][通常論文]
     
    A 56-year-old man was admitted for treatment of non-Hodgkin's lymphoma (NHL). He had undergone a partial small bowel and colon resection and had ileostomy due to bowel perforation induced by chemotherapy. After the operation, his disease status was in partial remission (PR), and reduced-intensity allogeneic stem cell transplantation (RIST) was therefore performed for further improvement of disease status. The conditioning regimen consisted of fludarabine and busulfan. Graft-versus-host disease (GVHD) prophylaxis was performed using cyclosporin and short-term methotrexate. The occurrence of serious infection during the period of neutropenia was prevented by the administration of amphotericin B, fluconazole and acyclovir. This case report provides important information on the appropriate strategy for treating patients who have ileostomy.
  • Kahata K, Asaka M, Miyazono K
    Nihon rinsho. Japanese journal of clinical medicine 63 Suppl 4 4 549 - 554 2005年04月 [査読無し][招待有り]
  • M Onozawa, S Hashino, K Izumiyama, K Kahata, M Chuma, A Mori, T Kondo, N Toyoshima, S Ota, S Kobayashi, S Hige, T Toubai, J Tanaka, M Imamura, M Asaka
    TRANSPLANTATION 79 5 616 - 619 2005年03月 [査読有り][通常論文]
     
    Reactivation of resolved hepatitis B virus (HBV) infection, which is known as reverse seroconversion (RS), has been reported as a rare complication of allogeneic hematopoietic stern cell transplantation. We retrospectively studied HBV serologic markers in 14 recipients with pretransplant ariti-hepatitis B surface antigen antibody (anti-HBs). Progressive decreases in anti-HBs titer were observed in all cases. In 12 cases, anti-HBs titer had decreased to under the protective value. RS occurred in seven cases after disappearance of anti-HBs. Although reseroconversion occurred in five cases, two cases remained in an HBV-carrier status after resolution of hepatitis. In the other five cases, RS did not occur even after disappearance of anti-HBs. The actual risks of anti-HBs disappearance and RS were estimated to be 75.0% and 39.8% at 2 years and 100.0% and 70.0% at 5 years, respectively. In conclusion, RS is a late-onset complication with high frequency that can be predicted by careful monitoring of progressive decrease in anti-HBs titer.
  • T Toubai, J Tanaka, T Higa, S Ota, M Ibata, Y Shono, S Mashiko, Y Miura, S Umehara, K Kahata, N Toyoshima, M Morioka, M Asaka, M Kasai, M Imamura
    AMERICAN JOURNAL OF HEMATOLOGY 78 1 67 - 70 2005年01月 [査読有り][通常論文]
     
    A case of a leukemic transformation following a 27-year history of idiopathic myelofibrosis (IMF) is presented. The patient had two chromosomal abnormalities: a deletion of chromosome 13, del 13(q12q14), and a deletion of chromosome 11, del 11 (q14q23). This patient's final diagnosis was acute micromegakaryocytic leukemia, and she died 1 month after leukemic transformation with an additional chromosomal abnormality, trisomy 8. IMF with myeloid metaplasia associated with deletion of the long arms of chromosomes 11 and 13 has not been previously reported. We speculate that the leukemic transformation in this patient was associated with chromosomal abnormalities del 11 and trisomy (C) 2004 Wiley-Liss, Inc.
  • T Toubai, J Tanaka, A Mori, S Hashino, S Kobayashi, S Ota, Y Miura, N Kato, K Kahata, K Izumiyama, M Yonezumi, K Chiba, T Kondo, N Toyoshima, M Asaka, M Imamura
    CLINICAL TRANSPLANTATION 18 5 552 - 557 2004年10月 [査読有り][通常論文]
     
    Introduction: A combination of fractionated total body irradiation (TBI) with etoposide (VP-16) and cyclophosphamide (CY) as a preconditioning regimen (VP/CY/TBI) has been reported to be safe and effective for both adults and children undergoing allogeneic bone marrow transplantation (allo-BMT). However, the reported doses of VP-16 were different. We evaluated the efficacy and safety of a VP-16 (at less than the usual dose)/CY/TBI regimen for adults with hematological malignancies who are required to receive allo-BMT. Patients and methods: Thirty-eight patients received VP-16, CY and TBI (VP/CY/TBI) as a preconditioning regimen for allo-BMT. Twenty-one patients were in first complete remission (1CR), six patients were in second remission (2CR) and 11 patients were in non-remission status (non-CR) before allo-BMT. These patients received allo-BMT from related donors (n = 14) and unrelated donors (n = 24). The preconditioning regimen consisted of VP-16 (15 mg/kg/d for 2 d), CY (60 mg/kg/d for 2 d) and 12 Gy TBI in six fractions for 3 d. Results: Two patients died on day 30 after transplantation. The median follow-up period for all patients was 35.0 months (range 0.8-159.6 months). At the time of analysis, 10 patients had died. Seven of those 10 patients died because of relapse. The estimated 5-yr disease-free survival (DFS) rates for all cases and acute myelogenous leukemia and acute lymphoblastic leukemia cases were 73.6, 66.7 and 100%, respectively. The estimated 5-yr DFS rates for 1CR, 2CR and non-CR cases were 90.5, 83.3 and 40.9%, respectively (p < 0.05). Conclusion: Based on these findings, we suggest that a VP/CY/TBI regimen is effective and safe for adult patients with hematological malignancies in 1CR and 2CR.
  • J Tanaka, T Toubai, Y Tsutsumi, Y Miura, N Kato, S Umehara, K Kahata, A Mori, N Toyoshima, S Ota, T Kobayashi, M Kobayashi, M Kasai, M Asaka, M Imamura
    BLOOD 104 3 768 - 774 2004年08月 [査読有り][通常論文]
     
    Inhibitory natural killer cell receptor (NKR)-expressing cells may induce a graft-versus-leukemia/tumor (GVL/T) effect against leukemic cells and tumor cells that have mismatched or decreased expression of HLA class I molecules and may not cause graft-versus-host disease (GVHD) against host cells that have normal expression of HLA class I molecules. In our study, we were able to expand inhibitory NKR (CD94/NKG2A)-expressing CD8(+) T cells from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs) by more than 500-fold using stimulation by an anti-CD3 monoclonal antibody with interleukin 15 (IL-15). These expanded and purified CD94-expressing cells attacked various malignant cell lines, including solid cancer cell lines, as well as the patients' leukemic cells but not autologous and allogeneic phytohemagglutinin (PHA) blasts in vitro. Also, these CD94-expressing cells prevented the growth of K562 leukemic cells and CW2 colon cancer cells in NOD/SCID mice in vivo. On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in mixed lymphocyte culture (MLC) and have high transforming growth factor (TGF)-beta1- but low IL-2-producing capacity. Therefore, CD94-expressing cells with cytolytic activity against the recipient's leukemic and tumor cells without enhancement of alloresponse might be able to be expanded from donor G-PBMCs.
  • S Ota, J Tanaka, K Kahata, T Toubai, K Kondo, A Mori, N Toyoshima, M Musashi, M Asaka, M Imamura
    INTERNATIONAL JOURNAL OF HEMATOLOGY 79 4 390 - 393 2004年05月 [査読有り][通常論文]
     
    We treated a 52-year-old woman with acute lymphoblastic leukemia (ALL) who developed invasive pulmonary aspergillosis (IPA) as a result of neutropenia following remission-induction chemotherapy Although serological test results, such as those for platelia and pastrex, were all negative and the serum level of beta-D-glucan was low, Aspergillus DNA was detected in blood by the polymerase chain reaction method. A clinically documented diagnosis of IPA was made on the basis of chest x-rays, computed tomography scan findings, and the detection of Aspergillus DNA. Micafungin (FK463), a candin class antifungal agent, was administered at a dose of 75 to 150 mg/day, because other antifungal agents were not effective. The increase in serum concentration of micafungin was dose-dependent and was accompanied by improvement of symptoms and objective findings. Micafungin was effective for the treatment of IPA in this patient with ALL. (C) 2004 The Japanese Society of Hematology.
  • K Kahata, M Hayashi, M Asaka, U Hellman, H Kitagawa, J Yanagisawa, S Kato, T Imamura, K Miyazono
    GENES TO CELLS 9 2 143 - 151 2004年02月 [査読有り][通常論文]
     
    Smad proteins are intracellular signalling mediators of transforming growth factor-beta (TGF-beta) superfamily. In the nucleus, activated Smad complexes regulate transcriptional responses of the target genes in cooperation with transcriptional coactivators and corepressors. To identify new components of transcriptional complexes containing Smad proteins, we purified DNA-binding proteins from human breast cancer MCF-7 cell nuclear extract using a Smad-binding DNA element as bait, and identified a coactivator GCN5 as a direct partner of activated Smad complexes. GCN5 is structurally similar to PCAF, which was previously identified as a coactivator for receptor-regulated Smads (R-Smads) for TGF-beta signalling pathways. GCN5 functions like PCAF, in that it binds to TGF-beta-specific R-Smads, and enhances transcriptional activity induced by TGF-beta. In addition, GCN5, but not PCAF, interacts with R-Smads for bone morphogenetic protein (BMP) signalling pathways, and enhances BMP-induced transcriptional activity, suggesting that GCN5 and PCAF have distinct physiological functions in vivo. Moreover, silencing of the GCN5 gene by RNA interference results in repression of transcriptional activities induced by TGF-beta. In conclusion we identified GCN5 as a Smad-binding transcriptional coactivator which positively regulates both TGF-beta and BMP signalling pathways.
  • S Hashino, A Mori, S Suzuki, K Izumiyama, K Kahata, M Yonezumi, K Chiba, T Kondo, S Ota, N Toyashima, N Kato, J Tanaka, M Imamura, M Asaka
    INTERNATIONAL JOURNAL OF HEMATOLOGY 77 2 188 - 191 2003年02月 [査読有り][通常論文]
     
    The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H pylori infection was found in 14 (63.6 %) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H pytori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 X 10(9)/L and an increase of more than 30 X 109/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H pylori reinfection. Another patient, in whom H pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H pylori eradication is not clear, the results of this study indicated that H pylori eradication treatment is a good option for some patients with chronic ITP. (C) 2003 The Japanese Society of Hematology.
  • J Tanaka, Y Tutumi, L Zhang, A Mori, K Kahata, N Toyoshima, S Ohta, S Kobayashi, S Hashino, M Asaka, M Imamura
    ACTA HAEMATOLOGICA 105 2 89 - 91 2001年 [査読有り][通常論文]
     
    In the present study, we investigated the inhibitory natural killer cell receptor (NKR) expression of CD94/NKG2A on PBMC after allogeneic bone marrow transplantation (BMI). The proportion of CD94 expression on PBMC was higher in patients without chronic graft-versus-host disease (cGVHD) and also in cGVHD patients with good response to conventional immunosuppressive therapy than in cGVHD patients with poor response. Also, the proportions of CD94+/CD3+ cells and CD94+/CD8+ cells were higher in cGVHD patients showing good response. In addition, the proportion of NKG2A-expressing cells was higher in patients without cGVHD than in patients with cGVHD. Therefore, chronic allostimulation after allo-BMT may augment the proportion of CD94/NKG2A-positive cells, and these cells may play some role in the regulation of alloresponse in some patients, Copyright (C) 2001 S. Karger AG, Basel.
  • A Mori, S Hashino, M Imamura, K Kahata, H Kawakami, M Shibata, S Kobayashi, J Tanaka, M Asaka
    BONE MARROW TRANSPLANTATION 21 6 615 - 617 1998年03月 [査読有り][通常論文]
     
    We report a case of bone marrow infarction in a 20-year-old woman with acute lymphocytic leukemia (ALL) who underwent unrelated bone marrow transplantation (BMT), Hematopoietic engraftment occurred on day 9 and, thereafter, the patient developed acute dermal and hepatic graft-versus-host disease (GVHD), She also experienced severe arthralgia in her knee joints on day 21, Immunosuppressive therapy with prednisolone (PSL) for acute GVHD was given, and the arthralgia improved rapidly, correlating with the improvement in dermal and hepatic GVHD, Based on the laboratory findings and analysis of magnetic resonance images, she was diagnosed as having bone marrow infarction, The cause of the bone marrow infarction was thought to be acute GVHD-related microangiopathy.
  • A Mori, S Hashino, M Imamura, K Kahata, H Kawakami, S Kobayashi, J Tanaka, M Musashi, M Asaka
    ACTA HAEMATOLOGICA 99 2 98 - 101 1998年 [査読有り][通常論文]
     
    We report a 46-year-old man suffering from angiocentric lymphoma of the skin. On admission, he had atypical cells rich in basophilic granules in the bone marrow and peripheral blood, in addition to skin eruptions and bone marrow dysplasia. Immediately after diagnosis, the patient was treated with multidrug combination chemotherapy. At first, the chemotherapy markedly relieved the skin eruption and bone marrow dysplasia, and atypical cells in the bone marrow and peripheral blood disappeared rapidly. However, the disease gradually became resistant to chemotherapy, resulting in a gradual deterioration of the skin eruption and bone marrow dysplasia, and reappearance of atypical cells. The levels of serum cytokines such as interleukin-4 and interleukin-6, and of soluble interleukin-2 receptor correlated well with the disease states. These results suggest that the lymphoma cells directly or indirectly induce the production of these cytokines and that a dysregulated cytokine network, which might be caused by lymphoma cells, induces an increase in atypical cells.
  • K Kahata, S Hashino, M Imamura, A Mori, S Kobayashi, M Asaka
    BONE MARROW TRANSPLANTATION 20 11 1001 - 1003 1997年12月 [査読有り][通常論文]
     
    A 34-year-old male suffered from an allergic reaction after inhalation of decontaminating drugs for BMT. Clinical challenge tests were undertaken to determine the causal drug. It was found that vancomycin hydrochloride (VCM) repeatedly induced dyspnea, fever, hypoxia, eosinophilia, and elevation of CRP. Therefore, clindamycin (CLDM) was used instead of VCM for decontamination of patient respiratory tract. Although complete decontamination of the respiratory tract was not achieved during the leukocytopenic period, BMT was successful, and there were no life-threatening infectious complications. Although inhaled VCM-induced allergic reaction mag be a very rare complication in the BMT setting, careful clinical attention should be paid to such patients.
  • 加畑馨, 橋野聡, 河上洋, 柴田美香, 盛暁生, 小林寿美子, 今村雅寛, 浅香正博
    無菌生物 27 2 98-100  1997年 [査読無し][通常論文]

MISC

  • Tomoyasu Jo, Tomoko Henzan, Daisuke Tomizawa, Satoru Yoshihara, Kaoru Kahata, Minami Yamada-Fujiwara, Yoshiki Okuyama, Norio Shiba, Keiko Fujii, Yoshihiro Umezawa, Rie Yamazaki, Wataru Takeda, Ryo Hanajiri, Kentaro Fukushima, Naoya Mimura, Junko Ikemoto, Keita Iwaki, Noboru Yonetani, Shin-Ichiro Fujiwara, Masaki Ri, Tokiko Nagamura-Inoue, Ryuji Tanosaki, Yasuyuki Arai [Rinsho ketsueki] The Japanese journal of clinical hematology 64 (5) 331 -337 2023年 
    The frequency of the manufacturing failure of chimeric antigen receptor (CAR)-T cell therapy in clinical practice is unknown. To clarify the current state of how likely CAR-T cell production is to succeed or fail for B-cell acute lymphoblastic leukemia (B-ALL), we analyzed cases in which the production of tisagenlecleucel was performed for patients with B-ALL at 15 facilities in Japan from October 2019 to March 2022. Total 81 patients (47 males and 34 females) were analyzed. The median age at apheresis was 13 years (1-25) with a median number of prior treatments of 4 (1-9). The numbers of patients with histories of allogeneic transplantation, inotuzumab ozogamicin, or blinatumomab treatments were 51 (63.0%), 26 (32.1%), and 37 (45.7%), respectively. The median blast percentage and CD3+ cell counts in peripheral blood were 0% (0-91.5), and 611/µl (35-4,210) at apheresis, and the median number of CD3+ cells shipped was 2.2×109 (0.5-8.3). While cases with a history of heavy prior treatment before apheresis were included, no manufacturing failures were observed. Continuing to monitor the status of manufacturing failures is necessary as the number of B-ALL cases treated with CAR-T cell therapy increases.
  • 安本 篤史, 加畑 馨, 豊嶋 崇徳 臨床検査 = Journal of clinical laboratory medicine 65 (12) 1310 -1316 2021年12月
  • Takahide Ara, Yuta Hasegawa, Hiroyuki Ohigashi, Souichi Shiratori, Atsushi Yasumoto, Hideki Goto, Junichi Sugita, Masahiro Onozawa, Masao Nakagawa, Kaoru Kahata, Daigo Hashimoto, Takanori Teshima BLOOD 138 2021年11月 
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  • AMLにおけるWT1発現量と染色体・遺伝子異常の関連
    日高 大輔, 小野澤 真弘, 橋口 淳一, 宮下 直洋, 笠原 耕平, 藤澤 真一, 早瀬 英子, 岡田 耕平, 白鳥 聡一, 後藤 秀樹, 杉田 純一, 中川 雅夫, 加畑 馨, 橋本 大吾, 遠藤 知之, 山本 聡, 堤 豊, 長谷山 美仁, 永嶋 貴博, 盛 暁生, 太田 秀一, 酒井 基, 石原 敏道, 今井 陽俊, 宮城島 拓人, 柿木 康孝, 黒澤 光俊, 小林 一, 岩崎 博, 清水 力, 近藤 健, 豊嶋 崇徳 臨床血液 59 (7) 964 -964 2018年07月 [査読無し][通常論文]
  • ステロイド抵抗性急性移植片対宿主病に対するヒト間葉系幹細胞療法の後方視的解析
    白鳥 聡一, 早瀬 英子, 岡田 耕平, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 中川 雅夫, 加畑 馨, 橋本 大吾, 遠藤 知之, 近藤 健, 豊嶋 崇徳 日本輸血細胞治療学会誌 64 (2) 452 -452 2018年04月 [査読無し][通常論文]
  • 加畑 馨 Frontiers in haemophilia 5 (1) 44 -47 2018年02月
  • 伊藤誠, 早瀬英子, 早瀬英子, 渡邊千秋, 上床貴代, 魚住諒, 林泰弘, 砂後谷華奈, 道又理恵, 早坂光司, 茂木祐子, 加畑馨, 加畑馨, 橋本大吾, 佐藤典宏, 豊嶋崇徳, 清水力 日本造血細胞移植学会総会プログラム・抄録集 40th 256 2017年12月11日 [査読無し][通常論文]
  • 中枢神経血管内リンパ腫の5例
    工藤 彰彦, 佐藤 翔紀, 佐藤 智香, 長沼 亮滋, 上床 尚, 白井 慎一, 高橋 育子, 松島 理明, 加納 崇裕, 矢部 一郎, 白鳥 聡一, 後藤 秀樹, 加畑 馨, 近藤 健, 佐々木 秀直 神経治療学 34 (6) S223 -S223 2017年11月 [査読無し][通常論文]
  • 中枢神経血管内リンパ腫の5例
    工藤 彰彦, 佐藤 翔紀, 佐藤 智香, 長沼 亮滋, 上床 尚, 白井 慎一, 高橋 育子, 松島 理明, 加納 崇裕, 矢部 一郎, 白鳥 聡一, 後藤 秀樹, 加畑 馨, 近藤 健, 佐々木 秀直 神経治療学 34 (6) S223 -S223 2017年11月 [査読無し][通常論文]
  • 岩井 孝仁, 西田 睦, 表原 里実, 薮崎 哲史, 小川 浩司, 岡村 圭祐, 平野 聡, 三橋 智子, 加畑 馨, 清水 力 超音波医学 44 (5) 447 -455 2017年09月 [査読無し][通常論文]
     
    症例は40歳代女性.主訴なし.前医にて肝S6の孤立性壊死性結節を経過観察中であった.造影CTにて,肝S6結節は経時的にほぼ消失したが,新たに肝S5に早期濃染を伴う10mmの腫瘤性病変を指摘された.超音波検査(US)とGd-EOB-DTPA造影MRIを施行し,悪性病変を否定できず,切除希望のため当院紹介となった.当院での初回USにて,肝S5に境界不明瞭な低エコー腫瘤を認め,Sonazoid造影超音波検査(CEUS)では,動脈相で微細点状の豊富な造影効果を認め,その後,結節状に強く造影された.門脈相で造影効果は遷延し,後血管相で造影効果は認めなかった.半年後のUSにて,肝S5腫瘤に増大はみられず,CEUS動脈相,後血管相に著変はなかったが,門脈相で早期の造影効果減弱を認めた.造影CTでも門脈相,平衡相の洗い出しが明瞭化した.これらの変化は肝細胞癌の脱分化など悪性病変を否定できず,腹腔鏡下肝部分切除術が施行された.病理組織学的所見では,被膜を有さない境界明瞭な腫瘤で,炎症細胞浸潤を背景に小血管の増生を伴っていた.免疫染色でαSMA陽性,ALK陰性,EBER陰性,IgG4陽性細胞をほとんど認めず,炎症性偽腫瘍(IPT)と診断された.IPTは特徴的な画像所見に乏しく,CEUSでIPTを経過観察し得た報告は少ない.今回,経時的にCEUS所見が変化したIPTの1症例を経験したので,若干の文献的考察を含めて報告する.(著者抄録)
  • 表原 里実, 西田 睦, 佐藤 恵美, 工藤 悠輔, 岩井 孝仁, 菊池 穏香, 倉島 庸, 木内 隆之, 外丸 詩野, 澁谷 斉, 加畑 馨, 清水 力 超音波検査技術 42 (Suppl.) S239 -S239 2017年06月
  • 岩井 孝仁, 西田 睦, 松井 雄一郎, 佐藤 恵美, 工藤 悠輔, 表原 里実, 高杉 莉佳, 船越 忠直, 岩崎 倫政, 澁谷 斉, 加畑 馨, 清水 力 超音波検査技術 42 (Suppl.) S282 -S282 2017年06月
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  • 山本桂子, 髭修平, 山本洋一, 中西満, 藤澤文絵, 小野澤真弘, 加畑馨, 中馬誠, 近藤健, 橋野聡, 渡部恵子, 大野稔子, 浅香正博, 田中淳司, 今村雅寛, 佐藤典宏, 小池隆夫 日本エイズ学会誌 9 (4) 537 -537 2007年11月20日 [査読無し][通常論文]
  • 小野澤真弘, 近藤健, 加畑馨, 橋野聡, 浅香正博 臨床血液 48 (9) 921 2007年09月30日 [査読無し][通常論文]
  • 守田玲菜, 加畑馨, 小野澤真弘, 近藤健, 橋野聡, 今村雅寛, 浅香正博 臨床血液 48 (9) 1108 2007年09月30日 [査読無し][通常論文]
  • 近藤健, 盛暁生, 小野澤真弘, 加畑馨, 橋野聡, 森岡正信, 今村雅寛, 浅香正博 臨床血液 48 (9) 923 2007年09月30日 [査読無し][通常論文]
  • 加畑馨, 佐藤典宏, 西尾充史, 太田秀一, 橋野聡, 今村雅寛, 浅香正博, 小池隆夫 日本輸血細胞治療学会誌 53 (1) 63 -64 2007年02月26日 [査読無し][通常論文]
  • 藤澤文絵, 近藤健, 橋野聡, 加畑馨, 渡部恵子, 大野稔子, 今村顕史, 浅香正博 日本エイズ学会誌 8 (4) 380 2006年11月20日 [査読無し][通常論文]
  • 荘拓也, 髭修平, 夏井坂光輝, 中西満, 加畑馨, 中馬誠, 近藤健, 太田秀一, 橋野聡, 渡部恵子, 大野稔子, 浅香正博, 田中淳司, 今村雅寛, 藤本勝也, 佐藤典宏, 小池隆夫 日本エイズ学会誌 8 (4) 346 -346 2006年11月20日 [査読無し][通常論文]
  • 川村孝仁, 川村孝仁, 中川雅夫, 小野澤真弘, 横山朗子, 加畑馨, 近藤健, 橋野聡, 浅香正博 臨床血液 47 (9) 1091 2006年09月30日 [査読無し][通常論文]
  • 小野澤真弘, 橋野聡, 金森弘恵, 加畑馨, 近藤健, 太田秀一, 田中淳司, 今村雅寛, 浅香正博 臨床血液 47 (9) 1207 2006年09月30日 [査読無し][通常論文]
  • 加畑馨, 金森弘恵, 小野澤真弘, 近藤健, 太田秀一, 小林寿美子, 橋野聡, 田中淳司, 今村雅寛, 浅香正博 臨床血液 47 (9) 1209 2006年09月30日 [査読無し][通常論文]
  • 近藤健, 小野沢真弘, 川村孝仁, 加畑馨, 橋野聡, 田中淳司, 今村雅寛, 浅香正博 臨床血液 46 (8) 902 2005年08月30日 [査読無し][通常論文]
  • 加畑馨, 高畑むつみ, 川村孝仁, 藤沢文絵, 近藤健, 小林寿美子, 橋野聡, 浅香正博, 今村雅寛, 藤田靖幸, 清水宏 臨床血液 46 (8) 964 2005年08月30日 [査読無し][通常論文]
  • 川村孝仁, 工藤大樹, 高畑むつみ, 小野沢真弘, 藤沢文絵, 泉山康, 加畑馨, 近藤健, 小林寿美子, 橋野聡, 浅香正博 臨床血液 46 (8) 966 2005年08月30日 [査読無し][通常論文]
  • 小野沢真弘, 橋野聡, 高畑むつみ, 川村孝仁, 藤沢文絵, 加畑馨, 近藤健, 太田秀一, 小林寿美子, 田中淳司, 今村雅寛, 高橋理明, 浅香正博 臨床血液 46 (8) 737 2005年08月30日 [査読無し][通常論文]
  • 加藤菜穂子, 杉田純一, 東梅友美, 近藤恵一, 太田秀一, 川村孝仁, 加畑馨, 近藤健, 橋野聡, 田中淳司, 浅香正博, 今村雅寛 臨床血液 46 (8) 926 2005年08月30日 [査読無し][通常論文]
  • S Hashino, A Mori, S Suzuki, K Izumiyama, K Kahata, M Yomezumi, K Chiba, T Kondo, S Ota, N Toyoshima, N Kato, J Tanaka, M Imamura, M Asaka BLOOD 98 (11) 755A -755A 2001年11月 [査読無し][通常論文]
  • 橋野聡, 盛暁生, 鈴木左知子, 泉山康, 加畑馨, 米積昌克, 加藤菜穂子, 田中淳司, 今村雅寛 臨床血液 42 (10) 949 2001年10月30日 [査読無し][通常論文]
  • 盛暁生, 加畑馨, 加藤貴司, 豊島経康, 橋野聡, 浅香正博, 小林寿美子, 田中淳司, 今村雅寛 Int J Hematol Suppl 73 (Supplement 1) 213 2001年03月 [査読無し][通常論文]
  • 加畑馨, 豊島経康, 太田秀一, 盛暁生, 橋野聡, 浅香正博, 田中淳司, 今村雅寛 Int J Hematol Suppl 73 (Supplement 1) 225 2001年03月 [査読無し][通常論文]
  • A Mori, J Tanaka, S Hashino, K Kahata, N Toyoshima, S Ota, Y Yamamoto, S Kobayashi, M Asaka, M Imamura BLOOD 96 (11) 305B -305B 2000年11月 [査読無し][通常論文]
  • J Tanaka, Y Tutumi, A Mori, K Kahata, N Toyoshima, S Ohta, M Asaka, M Imamura BLOOD 96 (11) 763A -763A 2000年11月 [査読無し][通常論文]
  • 盛暁生, 加畑馨, 豊島経康, 太田秀一, 橋野聡, 浅香正博, 小林寿美子, 田中淳司, 今村雅寛 臨床血液 41 (10) 1140 2000年10月30日 [査読無し][通常論文]

書籍等出版物

  • 再生医療等製品/遺伝子治療用製品の承認取得/審査の視点と実務戦略
    加畑 馨 (担当:分担執筆範囲:再生医療等製品の有効性評価における製造工程への着眼と品質管理)
    サイエンス&テクノロジー社 2020年09月

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 石森 直樹, 横田 卓, 加畑 馨
     
    近年わが国では急速な高齢化が進行してがん患者数は増加し、国民の２人に１人は生涯がんに罹患すると言われている。がんの早期発見や治療法の進歩により、がん患者の生命予後は著しく改善してきたが、再発がん患者では「がん死」に次いで死因第２位に「心血管病」が挙がっており、がん診療での心血管病の制御はきわめて重要な課題となっている。 アドリアマイシンをはじめとするアントラサイクリン系抗がん剤は、分子標的薬が登場した現代においてもリンパ腫、乳がんおよび肉腫などに対する標準的化学療法薬として重要な位置づけにある。しかし、累積使用量（アドリアマイシン換算）400mg/m2で約5％、700mg/m2では約25％と用量依存的に心筋障害を合併し、時に難治性心不全をきたして死に至る。疫学研究によって累積使用量のほか、年齢や放射線治療歴など心筋障害合併リスク因子が明らかにされているが、化学療法から年余を経て突然心不全を発症し、薬剤性心筋症と診断される例も少なくなく、細心の注意が必要である。 近年、加齢関連疾患の病態形成においていわゆる老化関連T細胞が出現する「免疫老化」の寄与が注目されている。我々はアドリアマイシン心筋症の発症・進展において「免疫老化」を基盤として慢性炎症が遷延し、心筋症発症に寄与するとの仮説を立てた。本研究の遂行によって、アドリアマイシン心筋症発症リスクのより正確な予測が可能となるばかりでなく、慢性炎症の制御という新たなコンセプトに基づくアドリアマイシン心筋症の予防・治療法の開発に貢献することが期待して本研究を立案した。 現在、標準的化学療法薬としてアドリアマイシンを用いたレジメで治療された悪性リンパ腫患者の治療フローを確認しながら、アドリアマイシン心筋症に関するレジストリ構築中である。

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