2020年11月, クラリベイト・アナリティクス, 高被引用論文著者 2020年 免疫学　　　　　　　　　　　　　　　

2019年11月, クラリベイト・アナリティクス, 高被引用論文著者 2019年　　　　　　　　　　　　　　　
免疫学
橋本 大吾

2018年11月, クラリベイト・アナリティクス, 高被引用論文著者 2018年　　　　　　　　　　　　　　　
免疫学
橋本 大吾

2017年11月, クラリベイト・アナリティクス, 高被引用論文著者 2017年　　　　　　　　　　　　　　　
免疫学
橋本 大吾

2016年11月, クラリベイト・アナリティクス, 高被引用論文著者 2016年　　　　　　　　　　　　　　　
免疫学
橋本 大吾

Early cardiotoxicity in post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis after HLA-haploidentical hematopoietic stem cell transplantation.
Toshihiro Matsukawa, Junichi Sugita, Daigo Hashimoto, Masayuki Aiba, Kohei Okada, Takanori Teshima
International journal of hematology, 2025年03月23日, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Post-transplant cyclophosphamide (PTCy)-based prophylaxis for graft-versus-host disease (GVHD) is widely used in HLA-haploidentical hematopoietic cell transplantation (haplo-HCT). One of the major drawbacks of PTCy is the risk of rare but potentially lethal cardiotoxicity, which prompted the development of regimens with reduced doses of PTCy. METHODS: We retrospectively compared the incidence of early cardiotoxicity with standard-dose of PTCy (cyclophosphamide 50 mg/kg/day for 2 days, PTCy100) versus reduced-dose (40 mg/kg/day for 2 days, PTCy80). In total, 179 patients underwent PTCy-based haplo-HCT, including PTCy100 (n = 111) and PTCy80 (n = 68). RESULTS: The PTCy80 group included significantly more elderly patients, patients who received reduced-intensity conditioning, and patients with a history of HCT than the PTCy100 group. Nine eligible patients (5.0%) experienced severe cardiotoxicity. The incidence of severe cardiotoxicity did not differ significant between PTCy80 and PTCy100 (4.4% vs. 5.4%; p = 1). The incidence of fatal cardiotoxicity was lower with PTCy80, but the small size may have prevented the difference from reaching statistical significance. CONCLUSION: Reducing the cyclophosphamide dose in PTCy-based GVHD prophylaxis may lower the risk of fatal cardiotoxicity without significantly altering the overall incidence of severe cardiotoxicity.

Chronic graft-versus-host disease myelitis successfully treated with rituximab.
Emi Yokoyama, Yuta Hasegawa, Kentaro Wakaki, Touma Suzuki, Sayaka Kajikawa, Minoru Kanaya, Koh Izumiyama, Makoto Saito, Masanobu Morioka, Jun Nagai, Tomoe Ichiki, Ryo Kikuchi, Satomi Okada, Hiroyuki Ohigashi, Hideki Goto, Masahiro Onozawa, Daigo Hashimoto, Akio Mori, Takanori Teshima, Takeshi Kondo
International journal of hematology, 2025年01月31日, ［国内誌］
英語, 研究論文（学術雑誌）, Chronic graft-versus-host disease (cGVHD) is a major serious complication after allogeneic stem-cell transplantation (allo-HSCT), and often mimics autoimmune diseases. Central nervous system (CNS) symptoms are rare manifestations of cGVHD, and are difficult to diagnose. CNS manifestations of cGVHD were discussed in the 2020 National Institutes of Health cGVHD Consensus Project as one of the "atypical cGVHD manifestations" with involvement of various organ systems other than classical cGVHD organs. We experienced a case of myelitis after allo-HSCT diagnosed as cGVHD of the CNS. The neurological symptoms progressed after corticosteroid pulse therapy, resulting in severe paralysis and paresthesia of the lower extremities. The clinical course and magnetic resonance imaging findings showed some similarities with multiple sclerosis. We decided to use rituximab after the patient became refractory to corticosteroids because rituximab has been reported to be effective in multiple sclerosis by suppressing B cells on both sides of the blood-brain barrier. Rituximab was effective for the neurologic symptoms in our case. In atypical cGVHD, treatments used in corresponding autoimmune diseases may be reasonable and effective.

FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML.
Toshihiro Matsukawa, Masahiro Onozawa, Takeshi Kondo, Minoru Kanaya, Daisuke Hidaka, Shuichi Ota, Akio Mori, Akio Shigematsu, Takuto Miyagishima, Yasutaka Kakinoki, Junichi Hashiguchi, Satoshi Yamamoto, Masayo Yamamoto, Kentaro Wakasa, Mutsumi Takahata, Toshimichi Ishihara, Yoshihito Haseyama, Akihito Fujimi, Tetsuya Igarashi, Takehiro Sarashina, Satoshi Iyama, Ryoji Kobayashi, Hajime Sakai, Katsuya Fujimoto, Junki Inamura, Yuji Kanisawa, Shinsuke Hirabayashi, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
Annals of hematology, 103, 12, 5333, 5340, 2024年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT.

Calcineurin inhibitor blocks tolerance by suppressing donor T cell terminal exhaustion after allogeneic hematopoietic cell transplantation.
Hajime Senjo, Daigo Hashimoto, Takanori Teshima
The Journal of clinical investigation, 134, 20, 2024年10月15日, ［国際誌］
英語, 研究論文（学術雑誌）

GVHD targets organoid-forming bile duct stem cells via a TGF-β-dependent manner.
Yuta Hasegawa, Daigo Hashimoto, Zixuan Zhang, Toru Miyajima, Yumika Saito, Wenyu Li, Ryo Kikuchi, Hajime Senjo, Tomoko Sekiguchi, Takahiro Tateno, Xuanzhong Chen, Emi Yokoyama, Shuichiro Takahashi, Hiroyuki Ohigashi, Takahide Ara, Eiko Hayase, Isao Yokota, Takanori Teshima
Blood, 2024年06月21日, ［国際誌］
英語, 研究論文（学術雑誌）, Graft-versus-host disease (GVHD) is a major life-threatening complication that occurs after allogeneic hematopoietic cell transplantation (HCT). While adult tissue stem cells have been identified as targets of GVHD in the skin and gut, their role in hepatic GVHD is yet to be clarified. In the current study, we explored the fate of bile duct stem cells (BDSCs), capable of generating liver organoids in vitro, during hepatic GVHD after allogeneic HCT. We observed a significant expansion of biliary epithelial cells (BECs) upon injury early after allogeneic HCT. Organoid-forming efficiency from the bile duct was also significantly increased early after allogeneic HCT. Subsequently, the organoid-forming efficiency from bile ducts was markedly decreased in association with the reduction of BECs and the elevation of plasma concentrations of bilirubin, suggesting that GVHD targets BDSCs and impairs the resilience of BECs. The growth of liver organoids in the presence of liver-infiltrating mononuclear cells from allogeneic recipients, but not from syngeneic recipients, significantly reduced in a TGF--dependent manner. Administration of SB-431542, an inhibitor of TGF-β signaling, from day 14 to day 28 protected organoid-forming BDSCs against GVHD and mitigated biliary dysfunction after allogeneic HCT, suggesting that BDSCs are a promising therapeutic target for hepatic GVHD.

Acute onset of constrictive pericarditis due to acute myelomonocytic leukemia: A case and literature review.
Naoki Kosaka, Takanori Uchiyama, Masahiro Onozawa, Jun Nagai, Jiro Koya, Suguru Ishizaka, Toshiyuki Nagai, Yohei Ikebe, Kenjiro Kato, Zen-Ichi Tanei, Jun Sakakibara-Konishi, Yuta Hasegawa, Hiroyuki Ohigashi, Hideki Goto, Daigo Hashimoto, Hideki Ujiie, Satoshi Hirano, Satoshi Konno, Toshihisa Anzai, Koji Taniguchi, Shinya Tanaka, Takanori Teshima
Internal medicine (Tokyo, Japan), 2024年04月16日, ［国内誌］
英語, 研究論文（学術雑誌）, We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after COVID-19 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified. This case indicates that leukemic infiltration can cause CP and that clinicians should include leukemia in the differential diagnosis of CP.

Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.
Yutaka Morishima, Masahito Kawabori, Kazuyoshi Yamazaki, Soichiro Takamiya, Sho Yamaguchi, Yo Nakahara, Hajime Senjo, Daigo Hashimoto, Sakiko Masuda, Yoichiro Fujioka, Yusuke Ohba, Yuki Mizuno, Yuji Kuge, Miki Fujimura
International journal of molecular sciences, 25, 4, 2024年02月18日, ［国際誌］
英語, 研究論文（学術雑誌）, Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 μg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.

再発難治性びまん性大細胞型B細胞リンパ腫に対するCAR-T細胞療法後にpseudo-progressionを認めた1例　　　　　　　　　　　　　　　
藤井 文彰, 千葉 雅尋, 橋田 里妙, 長谷川 祐太, 大東 寛幸, 安本 篤史, 後藤 秀樹, 山口 圭介, 小野澤 真弘, 橋本 大吾, 豊嶋 崇徳
臨床血液, 64, 12, 1523, 1524, (一社)日本血液学会-東京事務局, 2023年12月
日本語

HokUS-10 scoring system predicts the treatment outcome for sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation.
Souichi Shiratori, Kohei Okada, Junichi Sugita, Mutsumi Nishida, Takahito Iwai, Shuichi Ota, Daigo Hashimoto, Takanori Teshima
Scientific reports, 13, 1, 17374, 17374, 2023年10月13日, ［国際誌］
英語, 研究論文（学術雑誌）, Hepatic sinusoidal obstruction syndrome (SOS) is a severe and life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a multi-center retrospective study to evaluate the utility of our ultrasonographic scoring system for the diagnosis of SOS (HokUS-10) in predicting SOS-related mortality (SOS-RM). We analyzed a total of 42 patients who developed SOS after HSCT. The cumulative incidences of SOS-RM, non-relapse mortality (NRM), and overall survival at day 180 after the diagnosis of SOS were 26.4%, 28.8% and 54.5%, respectively. The area under the receiver operating characteristic curve analysis showed that the optimal cut-off value of HokUS-10 total score to predict SOS-RM was 8 points after the treatment of SOS. In the individual HokUS-10 score, ascites and portal vein flow-related scores (PV mean velocity and PV flow direction) after the treatment of SOS were shown as significant risk factors for SOS-RM. Our study suggested that US findings after the treatment can predict the treatment outcomes for SOS.

Incidence and course of Epstein-Barr virus viremia after allogeneic hematopoietic stem cell transplant for adult-onset systemic chronic active Epstein-Barr virus disease.
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, ［国際誌］
英語

Type 1 Cryoglobulinemic Vasculitis Due to Monoclonal Gammopathy of Undetermined Significance Successfully Treated by Bortezomib Plus Dexamethasone.
Ryo Kikuchi, Masahiro Onozawa, Jun Nagai, Satomi Okada, Yuta Hasegawa, Hiroyuki Ohigashi, Shintaro Mitamura, Taku Maeda, Emi Takakuwa, Yuichiro Fujieda, Hideki Goto, Daigo Hashimoto, Yoshihiro Matsuno, Takanori Teshima
Internal medicine (Tokyo, Japan), 2023年06月14日, ［国内誌］
英語, 研究論文（学術雑誌）, Cryoglobulins are immunoglobulins that precipitate in cold conditions. Type I cryoglobulinemic vasculitis is associated with hematological malignancies. We herein report a case of steroid-resistant type 1 cryoglobulinemic vasculitis associated with monoclonal gammopathy of undetermined significance (MGUS) in a 47-year-old woman. By immunofixation of cryoglobulin, we found that the main component of cryoglobulin was the M protein due to MGUS, so treatment of MGUS was needed. Bortezomib+dexamethasone therapy resulted in a rapid decrease in cryoglobulin and improvement in the symptoms of cryoglobulinemic vasculitis. In refractory type I cryoglobulinemic vasculitis, treatment of the underlying gammaglobulinopathy should be considered.

Calcineurin inhibitor inhibits tolerance induction by suppressing terminal exhaustion of donor T cells after allo-HCT.
Hajime Senjo, Shinpei Harada, Shimpei I Kubota, Yuki Tanaka, Takahiro Tateno, Zixuan Zhang, Satomi Okada, Xuanzhong Chen, Ryo Kikuchi, Naoki Miyashita, Masahiro Onozawa, Hideki Goto, Tomoyuki Endo, Yuta Hasegawa, Hiroyuki Ohigashi, Takahide Ara, Yoshinori Hasegawa, Masaaki Murakami, Takanori Teshima, Daigo Hashimoto
Blood, 2023年05月22日, ［国際誌］
英語, 研究論文（学術雑誌）, Calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis is standard in allogeneic hematopoietic stem cell transplantation (HCT) but fails to induce long-term tolerance without chronic GVHD in a considerable number of patients. In this study, we addressed this long-standing question in mouse models of HCT. After HCT, alloreactive donor T cells rapidly differentiated into PD-1+ TIGIT+ terminally exhausted T cells (terminal-Tex). GVHD prophylaxis with cyclosporine (CSP) suppressed donor T-cell expression of TOX, a master regulator to promote differentiation of transitory exhausted T cells (transitory-Tex), expressing both inhibitory receptors and effector molecules, into terminal-Tex, and inhibited tolerance induction. Adoptive transfer of transitory-Tex, but not terminal-Tex, into secondary recipients developed chronic GVHD. Transitory-Tex maintained alloreactivity and thus PD-1 blockade restored graft-versus-leukemia (GVL) activity of transitory-Tex, not terminal-Tex. In conclusion, CSP inhibits tolerance induction by suppressing the terminal exhaustion of donor T cells, while maintaining GVL effects to suppress leukemia relapse.

Subclinical minute FLT3-ITD clone can be detected in clinically FLT3-ITD-negative acute myeloid leukaemia at diagnosis.
Shota Yokoyama, Masahiro Onozawa, Shota Yoshida, Naoki Miyashita, Hiroyuki Kimura, Shogo Takahashi, Toshihiro Matsukawa, Hideki Goto, Shinichi Fujisawa, Kosuke Miki, Daisuke Hidaka, Junichi Hashiguchi, Kentaro Wakasa, Makoto Ibata, Yukari Takeda, Akio Shigematsu, Katsuya Fujimoto, Yutaka Tsutsumi, Akio Mori, Toshimichi Ishihara, Yasutaka Kakinoki, Takeshi Kondo, Daigo Hashimoto, Takanori Teshima
British journal of haematology, 201, 6, 1144, 1152, 2023年04月17日, ［国際誌］
英語, 研究論文（学術雑誌）, Recent advances in next-generation sequencing (NGS) have enabled the detection of subclinical minute FLT3-ITD. We selected 74 newly diagnosed, cytogenetically normal acute myeloid leukaemia (AML) samples in which FLT3-ITD was not detected by gel electrophoresis. We sequenced them using NGS and found minute FLT3-ITDs in 19 cases. We compared cases with clinically relevant FLT3-ITD (n = 37), cases with minute FLT3-ITD (n = 19) and cases without detectable FLT3-ITD (n = 55). Molecular characteristics (location and length) of minute FLT3-ITD were similar to those of clinically relevant FLT3-ITD. Survival of cases with minute FLT3-ITD was similar to that of cases without detectable FLT3-ITD, whereas the relapse rate within 1 year after onset was significantly higher in cases with minute FLT3-ITD. We followed 18 relapsed samples of cases with clinically FLT3-ITD-negative at diagnosis. Two of 3 cases with minute FLT3-ITD relapsed with progression to clinically relevant FLT3-ITD. Two of 15 cases in which FLT3-ITD was not detected by NGS relapsed with the emergence of minute FLT3-ITD, and one of them showed progression to clinically relevant FLT3-ITD at the second relapse. We revealed the clonal dynamics of subclinical minute FLT3-ITD in clinically FLT3-ITD-negative AML. Minute FLT3-ITD at the initial AML can expand to become a dominant clone at relapse.

Subcutaneous Panniculitis-like T-cell Lymphoma Lacking Subcutaneous Tumor Mimicking Adult-onset Still's Disease.
Maria Tada, Shion Kachi, Masahiro Onozawa, Yuichiro Fujieda, Shota Yoshida, Yotaro Oki, Kazuro Kamada, Jun Nagai, Satomi Okada, Ryo Kikuchi, Ryo Hisada, Yuta Hasegawa, Hiroyuki Ohigashi, Hideki Goto, Daigo Hashimoto, Shinichi Nakazato, Yoshihiro Matsuno, Takanori Teshima, Tatsuya Atsumi
Internal medicine (Tokyo, Japan), 2023年03月15日, ［国内誌］
英語, 研究論文（学術雑誌）, We herein report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) resembling adult-onset Still's disease (AOSD). A 40-year-old woman presented with a fever, erythema, and painful subcutaneous nodules on the trunk. Laboratory data and a bone marrow analysis showed hemophagocytic syndrome. Although AOSD was suspected, based on a histopathological evaluation of the erythema, she was diagnosed with SPTCL. She was refractory to combination chemotherapy but achieved durable remission with cyclosporine monotherapy. Genetic testing revealed a homozygous HAVCR2 c.245A>G variant (rs184868814) that had caused NLRP3 inflammasome activation. SPTCL and AOSD share a pathogenesis in terms of NLRP3 inflammasome activation, so the clinical phenotype of SPTCL reasonably mimics AOSD.

Decreased Paneth cell α-defensins promote fibrosis in a choline-deficient L-amino acid-defined high-fat diet-induced mouse model of nonalcoholic steatohepatitis via disrupting intestinal microbiota
Shunta Nakamura, Kiminori Nakamura, Yuki Yokoi, Yu Shimizu, Shuya Ohira, Mizu Hagiwara, Zihao Song, Li Gan, Tomoyasu Aizawa, Daigo Hashimoto, Takanori Teshima, Andre J. Ouellette, Tokiyoshi Ayabe
Scientific Reports, 13, 1, Springer Science and Business Media LLC, 2023年03月09日
研究論文（学術雑誌）, Abstract

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fibrosis that develops from fatty liver. Disruption of intestinal microbiota homeostasis, dysbiosis, is associated with fibrosis development in NASH. An antimicrobial peptide α-defensin secreted by Paneth cells in the small intestine is known to regulate composition of the intestinal microbiota. However, involvement of α-defensin in NASH remains unknown. Here, we show that in diet-induced NASH model mice, decrease of fecal α-defensin along with dysbiosis occurs before NASH onset. When α-defensin levels in the intestinal lumen are restored by intravenous administration of R-Spondin1 to induce Paneth cell regeneration or by oral administration of α-defensins, liver fibrosis is ameliorated with dissolving dysbiosis. Furthermore, R-Spondin1 and α-defensin improved liver pathologies together with different features in the intestinal microbiota. These results indicate that decreased α-defensin secretion induces liver fibrosis through dysbiosis, further suggesting Paneth cell α-defensin as a potential therapeutic target for NASH.

Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation.
Roni Shouval, Nicholas R Waters, Antonio L C Gomes, Corrado Zuanelli Brambilla, Teng Fei, Sean M Devlin, Chi L Nguyen, Kate A Markey, Anqi Dai, John B Slingerland, Annelie G Clurman, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Tobias M Hohl, Ying Taur, Anthony D Sung, Daniela Weber, Daigo Hashimoto, Takanori Teshima, Nelson J Chao, Ernst Holler, Michael Scordo, Sergio A Giralt, Miguel-Angel Perales, Jonathan U Peled, Marcel R M van den Brink
Clinical cancer research : an official journal of the American Association for Cancer Research, 29, 1, 165, 173, 2023年01月04日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The gut microbiota is subject to multiple insults in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. We hypothesized that preparative conditioning regimens contribute to microbiota perturbation in allo-HCT. EXPERIMENTAL DESIGN: This was a retrospective study that evaluated the relationship between conditioning regimens exposure in 1,188 allo-HCT recipients and the gut microbiome. Stool samples collected from 20 days before transplantation up to 30 days after were profiled using 16S rRNA sequencing. Microbiota injury was quantified by changes in α-diversity. RESULTS: We identified distinct patterns of microbiota injury that varied by conditioning regimen. Diversity loss was graded into three levels of conditioning-associated microbiota injury (CMBI) in a multivariable model that included antibiotic exposures. High-intensity regimens, such as total body irradiation (TBI)-thiotepa-cyclophosphamide, were associated with the greatest injury (CMBI III). In contrast, the nonmyeloablative regimen fludarabine-cyclophosphamide with low-dose TBI (Flu/Cy/TBI200) had a low-grade injury (CMBI I). The risk of acute GVHD correlated with CMBI degree. Pretransplant microbial compositions were best preserved with Flu/Cy/TBI200, whereas other regimens were associated with loss of commensal bacteria and expansion of Enterococcus. CONCLUSIONS: Our findings support an interaction between conditioning at the regimen level and the extent of microbiota injury.

Separation of GVL from GVHD -location, location, location.
Takanori Teshima, Daigo Hashimoto
Frontiers in immunology, 14, 1296663, 1296663, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for various hematologic malignancies. However, alloimmune response is a double-edged sword that mediates both beneficial graft-versus-leukemia (GVL) effects and harmful graft-versus-host disease (GVHD). Separation of GVL effects from GVHD has been a topic of intense research to improve transplant outcomes, but reliable clinical strategies have not yet been established. Target tissues of acute GVHD are the skin, liver, and intestine, while leukemic stem cells reside in the bone marrow. Tissue specific effector T-cell migration is determined by a combination of inflammatory and chemotactic signals that interact with specific receptors on T cells. Specific inhibition of donor T cell migration to GVHD target tissues while preserving migration to the bone marrow may represent a novel strategy to separate GVL from GVHD. Furthermore, tissue specific GVHD therapy, promoting tissue tolerance, and targeting of the tumor immune microenvironment may also help to separate GVHD and GVL.

Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota.
Xuanzhong Chen, Daigo Hashimoto, Ko Ebata, Shuichiro Takahashi, Yu Shimizu, Ryuga Shinozaki, Yuta Hasegawa, Ryo Kikuchi, Hajime Senjo, Kazuki Yoneda, Zixuan Zhang, Shinpei Harada, Eiko Hayase, Takahide Ara, Hiroyuki Ohigashi, Yoichiro Iwakura, Kiminori Nakamura, Tokiyoshi Ayabe, Takanori Teshima
Proceedings of the National Academy of Sciences of the United States of America, 119, 48, e2211230119, 2022年11月29日, ［国際誌］
英語, 研究論文（学術雑誌）, Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1-/- mice, and adoptive transfer of wild-type (WT) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.

Unilateral recurrent laryngeal nerve palsy detected by PET/CT in a patient with mediastinal T-cell lymphoblastic lymphoma.
Toru Miyajima, Yuta Hasegawa, Daigo Hashimoto, Takanori Teshima
International journal of hematology, 116, 1, 3, 4, 2022年07月, ［国内誌］
英語

High CRP-albumin ratio predicts poor prognosis in transplant ineligible elderly patients with newly diagnosed acute myeloid leukemia.
Hajime Senjo, Masahiro Onozawa, Daisuke Hidaka, Shota Yokoyama, Satoshi Yamamoto, Yutaka Tsutsumi, Yoshihito Haseyama, Takahiro Nagashima, Akio Mori, Shuichi Ota, Hajime Sakai, Toshimichi Ishihara, Takuto Miyagishima, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Hajime Kobayashi, Hiroshi Iwasaki, Daigo Hashimoto, Takeshi Kondo, Takanori Teshima
Scientific reports, 12, 1, 8885, 8885, 2022年05月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Acute myeloid leukemia (AML) patients older than 65 years have a poor prognosis. Recently, CAR (C-reactive-protein/albumin ratio) has been actively reported as a prognostic index reflecting the nutritional and inflammatory status of elderly patients with solid tumors, but the usefulness of this index as a prognostic indicator in transplant-ineligible elderly AML patients has not been investigated. We studied genetic alterations and CARs in 188 newly diagnosed AML patients aged 65 years or older who were treated in a multicenter setting and had treated without HSCT. Both NCCN 2017 risk group, reflecting the genetic component of the tumor, and CAR, reflecting the inflammatory and nutritional status of the patient, successfully stratified the overall survival (OS) of the patients (2-year OS; CAR low vs high, 42.3% vs 17.8%, P < 0.001). Furthermore, in multivariate analysis, NCCN 2017 poor group and high CAR were extracted as independent poor prognostic factors predicting 2-year OS in the current study. We found, for the first time, that CAR at diagnosis predicted the prognosis of elderly patients with newly diagnosed AML treated without HSCT.

Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation.
Zixuan Zhang, Yuta Hasegawa, Daigo Hashimoto, Hajime Senjo, Ryo Kikuchi, Xuanzhong Chen, Kazuki Yoneda, Tomoko Sekiguchi, Tatsuya Kawase, Hirofumi Tsuzuki, Takashi Ishio, Takahide Ara, Hiroyuki Ohigashi, Masao Nakagawa, Takanori Teshima
Bone marrow transplantation, 57, 5, 775, 780, 2022年05月, ［国際誌］
英語, 研究論文（学術雑誌）, Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative therapy for FLT3 internal tandem duplication mutant (FLT3-ITD+) acute myeloid leukemia, but relapse rate is high. A recent study showed that sorafenib, a first generation FLT3 and multikinase inhibitor, enhanced graft-versus-leukemia (GVL) effects against FLT3-ITD+ leukemia via interleukin-15 (IL-15) production. However, it remains to be clarified whether this effect could be mediated by selective FLT3 inhibition. We investigated whether gilteritinib, a selective FLT3 inhibitor, could enhance GVL effects against FLT3-ITD transfected Ba/F3 leukemia (Ba/F3-FLT3-ITD) in mice. Oral administration of gilteritinib from day +5 to +14 after allo-SCT reduced expression of the co-inhibitory receptors PD-1 and TIGIT on donor CD8+ T cells and enhanced IL-15 expression in Ba/F3-FLT3-ITD. Bioluminescent imaging using luciferase-transfected Ba/F3-FLT3-ITD demonstrated that gilteritinib significantly suppressed leukemia expansion after allo-SCT, whereas it did not impact the morbidity or mortality of graft-versus-host disease (GVHD), resulting in significant improvement of overall survival. In conclusion, short-term administration of gilteritinib after allo-SCT enhanced GVL effects against FLT3-ITD+ leukemia without exacerbating GVHD.

Rescue Extracranial–Intracranial Bypass for Ischemic Stroke Secondary to Progressive Human Immunodeficiency Virus–Associated Vasculopathy
Makoto Mizushima, Taku Sugiyama, Katsuki Eguchi, Monami Tarisawa, Kikutaro Tokairin, Masaki Ito, Daigo Hashimoto, Ichiro Yabe, Miki Fujimura
Journal of Neurological Surgery Part A: Central European Neurosurgery, 85, 01, 088, 093, Georg Thieme Verlag KG, 2022年02月22日
研究論文（学術雑誌）, Abstract

Background Human immunodeficiency virus (HIV) associated vasculopathy can cause ischemic cerebral stroke; however, there is limited evidence on optimal management. Herein, we report a case of acute ischemic stroke due to progressive internal carotid artery (ICA) stenosis in an HIV-positive patient. Superficial temporal artery to middle cerebral artery (STA-MCA) bypass, in addition to the best medical treatments, prevented stroke progression.

Clinical Description A 39-year-old man with HIV infection presented with a sudden onset of aphasia and right hemiparesis. Magnetic resonance imaging revealed an ischemic lesion in the left basal ganglia and concentric thickening of the vessel wall in the terminal portion of the bilateral ICAs. Despite maximal medical treatments for HIV-associated vasculopathy and possible opportunistic infections, bilateral ICA stenoses progressed, leading to a second hemodynamic stroke event. Because tissue plasminogen activator treatment failed, we performed STA-MCA bypass. A significant improvement in neurologic symptoms and cerebral blood flow was observed after surgery. No further stroke events occurred during the continuation of medical treatments.

Conclusion This is the first case of STA-MCA bypass performed in a patient with recurrent ischemic stroke caused by HIV-associated vasculopathy. Although further evidence is needed, such treatment options can shed new light on the management of progressive HIV-associated vasculopathy, which is refractory to maximal medical treatment.

HIV関連悪性リンパ腫の臨床的特徴
遠藤 知之, 後藤 秀樹, 荒 隆英, 長谷川 祐太, 横山 翔大, 高橋 承吾, 米田 和樹, 橋本 大吾, 橋野 聡, 豊嶋 崇徳
日本エイズ学会誌, 24, 1, 13, 20, (一社)日本エイズ学会, 2022年02月
日本語

[Bing-Neel syndrome successfully treated with tirabrutinib].
Keito Yokoyama, Hiroyuki Ohigashi, Toru Miyajima, Naoki Miyashita, Satomi Okada, Yuta Hasegawa, Junichi Sugita, Masahiro Onozawa, Daigo Hashimoto, Takanori Teshima
[Rinsho ketsueki] The Japanese journal of clinical hematology, 63, 8, 870, 875, 2022年, ［国内誌］
日本語, 研究論文（学術雑誌）, Bing-Neel syndrome (BNS) is a rare disease manifestation of Waldenström's macroglobulinemia characterized by abnormal lymphoplasmacytoid cells infiltration of the central nervous system. In September 2019, a 46-year-old man presented to a previous hospital with hand tremors, nausea, and dysuria. Demyelination of cerebral white matter and the spinal cord was discovered using MRI. Steroid pulse therapy was used to treat inflammatory demyelinating disease, and it provided temporary relief, but the symptoms returned when the steroids were stopped. He was referred to our hospital in June 2020, for further evaluation with the possibility of hematological malignancy. BNS was diagnosed based on the presence of abnormal lymphoplasmacytoid cells in the bone marrow and cerebrospinal fluid (CSF), as well as the presence of the MYD88L265P mutation in the CSF specimen. In July 2020, BR (bendamustine, rituximab) therapy was administered, but it was ineffective. Oral administration of tirabrutinib, which was recently approved for WM, began in August 2020. He has achieved long-term remission and steroid withdrawal, with no notable side effects. This is the second report of successful treatment of BNS with tirabrutinib. More research is needed to confirm tirabrutinib's efficacy in the treatment of BNS.

Intravenous transplantation of amnion-derived mesenchymal stem cells promotes functional recovery and alleviates intestinal dysfunction after spinal cord injury.
Soichiro Takamiya, Masahito Kawabori, Kazuyoshi Yamazaki, Sho Yamaguchi, Aki Tanimori, Koji Yamamoto, Shunsuke Ohnishi, Toshitaka Seki, Kotaro Konno, Khin Khin Tha, Daigo Hashimoto, Masahiko Watanabe, Kiyohiro Houkin, Miki Fujimura
PloS one, 17, 7, e0270606, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Spinal cord injury (SCI) is often accompanied by gastrointestinal dysfunction due to the disconnection of the spinal autonomic nervous system. Gastrointestinal dysfunction reportedly upregulates intestinal permeability, leading to bacterial translocation of the gut microbiome to the systemic circulation, which further activates systemic inflammation, exacerbating neuronal damage. Mesenchymal stem cells (MSC) reportedly ameliorate SCI. Here, we aimed to investigate their effect on the associated gastrointestinal dysfunction. Human amnion-derived MSC (AMSCs) were intravenously transplanted one day after a rat model of midthoracic SCI. Biodistribution of transplanted cells, behavioral assessment, and histological evaluations of the spinal cord and intestine were conducted to elucidate the therapeutic effect of AMSCs. Bacterial translocation of the gut microbiome was examined by in situ hybridization and bacterial culture of the liver. Systemic inflammations were examined by blood cytokines, infiltrating immune cells in the spinal cord, and the size of the peripheral immune tissue. AMSCs released various neurotrophic factors and were mainly distributed in the liver and lung after transplantation. AMSC-transplanted animals showed smaller spinal damage and better neurological recovery with preserved neuronal tract. AMSCs transplantation ameliorated intestinal dysfunction both morphologically and functionally, which prevented translocation of the gut microbiome to the systemic circulation. Systemic inflammations were decreased in animals receiving AMSCs in the chronic phase. Intravenous AMSC administration during the acute phase of SCI rescues both spinal damage and intestinal dysfunction. Reducing bacterial translocation may contribute to decreasing systemic inflammation.

Aleukemic Extramedullary Blast Crisis as an initial presentation of Chronic Myeloid Leukemia with E1A3 BCR-ABL1 Fusion Transcript
Naoki Miyashita, Masahiro Onozawa, Keito Suto, Shinichi Fujisawa, Nanase Okazaki, Daisuke Hidaka, Hiroyuki Ohigashi, Atsushi Yasumoto, Junichi Sugita, Daigo Hashimoto, Yoshihiro Matsuno, Takanori Teshima
Internal Medicine, 61, 7, 1049, 1054, Japanese Society of Internal Medicine, 2022年, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Right neck swelling and pain occurred in a 49-year-old man. A Blood count showed a slight increase in platelet count without leukemoid reaction. After a biopsy of the cervical mass and bone marrow aspiration, a diagnosis of extramedullary blast crisis (EBC) of chronic myeloid leukemia (CML) was made. FISH analysis showed a BCR-ABL1 fusion signal, but results of RT-PCR for major and minor BCR-ABL1 transcripts were negative. We identified a rare e1a3 BCR-ABL1 fusion transcript. Administration of dasatinib resulted in disappearance of the extramedullary tumor. This is the first reported case of CML-EBC with e1a3 transcript. An aleukemic extramedullary tumor can be the initial presentation of CML.

Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors
Souichi Shiratori, Junichi Sugita, Shigeo Fuji, Jun Aoki, Masashi Sawa, Yukiyasu Ozawa, Daigo Hashimoto, Ken-ichi Matsuoka, Kazunori Imada, Noriko Doki, Takashi Ashida, Yasunori Ueda, Masatsugu Tanaka, Yasushi Sawayama, Tatsuo Ichinohe, Seitaro Terakura, Satoko Morishima, Yoshiko Atsuta, Takahiro Fukuda, Takanori Teshima
Bone Marrow Transplantation, 56, 9, 2231, 2240, Springer Science and Business Media LLC, 2021年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Antithymocyte globulin (ATG) has been shown to reduce chronic graft-versus-host disease (GVHD) particularly in allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors; however, anti-GVHD effects of lower doses of ATG remains to be elucidated. We conducted a nationwide retrospective study to compare the outcomes of unrelated PBSCT with or without rabbit ATG (thymoglobulin) in 287 patients. A median ATG dose was 2.0 mg/kg. The primary endpoint, the cumulative incidence of moderate-severe chronic GVHD at 2 years was 22.1% in the ATG group, which was significantly less than that in the non-ATG group (36.3%, P = 0.025). The ATG group had a higher incidence of immunosuppressant discontinuation, GVHD-free, relapse-free survival, and moderate-severe chronic GVHD-free, relapse-free survival at 2 years compared to the non-ATG group. The incidences of grade III-IV aGVHD and moderate-severe chronic GVHD were significantly higher in patients with high absolute lymphocyte count (ALC) before the administration of ATG, whereas relapse rate was significantly higher in patients with low ALC before ATG. In conclusion, low-dose ATG effectively suppresses chronic GVHD in unrelated PBSCT, and ALC before ATG may be a potential predictor for GVHD and relapse.

Novel Insights Into the Mechanism of GVHD-Induced Tissue Damage
Takahide Ara, Daigo Hashimoto
Frontiers in Immunology, 12, Frontiers Media SA, 2021年08月27日, ［査読有り］, ［招待有り］, ［最終著者, 責任著者］
英語, 研究論文（学術雑誌）, Prophylaxis for and treatment of graft-versus-host disease (GVHD) are essential for successful allogeneic hematopoietic stem cell transplantation (allo-SCT) and mainly consist of immunosuppressants such as calcineurin inhibitors. However, profound immunosuppression can lead to tumor relapse and infectious complications, which emphasizes the necessity of developing novel management strategies for GVHD. Emerging evidence has revealed that tissue-specific mechanisms maintaining tissue homeostasis and promoting tissue tolerance to combat GVHD are damaged after allo-SCT, resulting in exacerbation and treatment refractoriness of GVHD. In the gastrointestinal tract, epithelial regeneration derived from intestinal stem cells (ISCs), a microenvironment that maintains healthy gut microbiota, and physical and chemical mucosal barrier functions against pathogens are damaged by conditioning regimens and/or GVHD. The administration of growth factors for cells that maintain intestinal homeostasis, such as interleukin-22 (IL-22) for ISCs, R-spondin 1 (R-Spo1) for ISCs and Paneth cells, and interleukin-25 (IL-25) for goblet cells, mitigates murine GVHD. In this review, we summarize recent advances in the understanding of GVHD-induced tissue damage and emerging strategies for the management of GVHD.

高用量DPP-4阻害薬を用いた同種造血幹細胞移植後の移植片対宿主病予防　　　　　　　　　　　　　　　
橋本 大吾
血液内科, 83, 2, 270, 274, 2021年08月, ［招待有り］, ［筆頭著者］
日本語, 研究論文（その他学術会議資料等）

XIAP欠損症に対して非血縁者間骨髄移植を施行して移植後赤芽球癆を認めた1例　　　　　　　　　　　　　　　
千葉 雅尋, 杉田 純一, 宮下 直樹, 須藤 啓斗, 日高 大輔, 大東 寛幸, 安本 篤史, 小野澤 真弘, 橋本 大吾, 豊嶋 崇徳
臨床血液, 62, 7, 848, 849, (一社)日本血液学会-東京事務局, 2021年07月
日本語

髄外腫瘤で発症したe1a3 BCR-ABL陽性慢性骨髄性白血病　　　　　　　　　　　　　　　
宮下 直樹, 小野澤 真弘, 須藤 啓斗, 日高 大輔, 大東 寛幸, 安本 篤史, 杉田 純一, 橋本 大吾, 豊嶋 崇徳
臨床血液, 62, 7, 849, 849, (一社)日本血液学会-東京事務局, 2021年07月
日本語

High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease
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, Springer Science and Business Media LLC, 2021年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Extramedullary hematopoiesis of the cranial dura
Keito Suto, Junichi Sugita, Daigo Hashimoto, Hiroyuki Kameda, Tomoko Mitsuhashi, Takanori Teshima
International Journal of Hematology, 113, 3, 315, 317, Springer Science and Business Media LLC, 2021年03月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）

急性GVHDの病態　　　　　　　　　　　　　　　
橋本 大吾
炎症と免疫, 29, 2, 137, 142, 2021年02月, ［招待有り］, ［筆頭著者］
日本語, 研究論文（その他学術会議資料等）

[Emergence of mutation in the colony-stimulating factor 3 receptor gene during follow-up of unclassifiable myeloproliferative neoplasm].
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, ［国内誌］
日本語, 研究論文（学術雑誌）, 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.

急性前骨髄球性白血病に対する同種造血幹細胞移植27年後に発症したドナー細胞由来未分化大細胞リンパ腫の1例　　　　　　　　　　　　　　　
菊池 遼, 小野澤 真弘, 今本 鉄平, 高橋 秀一郎, 杉田 純一, 橋本 大吾, 橋野 聡, 松野 吉宏, 豊嶋 崇徳
日本内科学会雑誌, 110, 1, 92, 98, (一社)日本内科学会, 2021年01月
日本語

A novel nutritional index “simplified CONUT” and the disease risk index independently stratify prognosis of elderly patients with acute myeloid leukemia
Hajime Senjo, Masahiro Onozawa, Daisuke Hidaka, Shota Yokoyama, Satoshi Yamamoto, Yutaka Tsutsumi, Yoshihito Haseyama, Takahiro Nagashima, Akio Mori, Shuichi Ota, Hajime Sakai, Toshimichi Ishihara, Takuto Miyagishima, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Hajime Kobayashi, Hiroshi Iwasaki, Daigo Hashimoto, Takeshi Kondo, Takanori Teshima
Scientific Reports, 10, 1, 19400, 19400, Springer Science and Business Media LLC, 2020年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）,
Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

同種造血幹細胞移植後の腸内細菌叢の変化が臨床成績に及ぼす影響　　　　　　　　　　　　　　　
橋本 大吾
血液内科, 81, 5, 707, 712, 2020年11月, ［招待有り］, ［筆頭著者］
日本語, 研究論文（その他学術会議資料等）

Validation and comparison of prognostic values of GNRI, PNI, and CONUT in newly diagnosed diffuse large B cell lymphoma.
Toshihiro Matsukawa, Keito Suto, Minoru Kanaya, Koh Izumiyama, Koichiro Minauchi, Shota Yoshida, Hisashi Oda, Takuto Miyagishima, Akio Mori, Shuichi Ota, Daigo Hashimoto, Takanori Teshima
Annals of hematology, 99, 12, 2859, 2868, 2020年09月24日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Diffuse large B cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma. Emerging evidence indicates that poor nutritional status determined with nutritional indices such as geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) was associated with poor prognosis of DLBCL. We conducted this multicenter retrospective study to validate and compare prognostic values of the three indices in 615 newly diagnosed DLBCL patients. The overall survival (OS) in patients with poor nutritional status determined with each of these nutritional indices were significantly inferior compared with that in those without nutritional risks (5-year OS in patients with GNRI < 95.7 and GNRI ≥ 95.7 were 56.4% and 83.5%, P < 0.001; PNI < 42.4 and PNI ≥ 42.4 were 56.1% and 81.0%, P < 0.001; CONUT > 4 and CONUT ≤ 4 were 53.1% and 77.1%, P < 0.001). GNRI and CONUT were independent prognostic predictors for OS (GNRI < 95.7, hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.22-2.74, P = 0.0032; CONUT > 4, HR 1.53, 95% CI 1.05-2.23, P = 0.028) after multivariate analyses. Nutritional status determined with GNRI affected OS more strongly in the patients with nongerminal center B cell-like (nonGCB) DLBCL compared with that in those with GCB-type DLBCL. In conclusion, baseline poor nutritional status determined based on GNRI or CONUT was an independent risk factor of newly diagnosed DLBCL, and GNRI was also useful as an independent prognostic factor for patients with nonGCB-type DLBCL.

Feasibility and efficacy of low-dose pegfilgrastim for CD34+ cell mobilization in lymphoma.
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, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

同種造血幹細胞移植における免疫チェックポイント阻害薬
橋本 大吾
日本造血細胞移植学会雑誌, 9, 1, 13, 22, The Japan Society for Hematopoietic Stem Cell Transplantation, 2020年09月, ［査読有り］, ［招待有り］, ［筆頭著者］
日本語, 研究論文（学術雑誌）

Intestinal goblet cells protect against GVHD after allogeneic stem cell transplantation via Lypd8.
Takahide Ara, Daigo Hashimoto, Eiko Hayase, Clara Noizat, Ryo Kikuchi, Yuta Hasegawa, Kana Matsuda, Shoko Ono, Yoshihiro Matsuno, Ko Ebata, Reiki Ogasawara, Shuichiro Takahashi, Hiroyuki Ohigashi, Emi Yokoyama, Keitaro Matsuo, Junichi Sugita, Masahiro Onozawa, Ryu Okumura, Kiyoshi Takeda, Takanori Teshima
Science translational medicine, 12, 550, 2020年07月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Graft-versus-host disease (GVHD) and infection are major obstacles to successful allogeneic hematopoietic stem cell transplantation (HSCT). Intestinal goblet cells form the mucus layers, which spatially segregate gut microbiota from host tissues. Although it is well known that goblet cell loss is one of the histologic features of GVHD, effects of their loss in pathophysiology of GVHD remain to be elucidated. In mouse models of allogeneic HSCT, goblet cells in the colon were significantly reduced, resulting in disruption of the inner mucus layer of the colon and increased bacterial translocation into colonic mucosa. Pretransplant administration of interleukin-25 (IL-25), a growth factor for goblet cells, protected goblet cells against GVHD, prevented bacterial translocation, reduced plasma concentrations of interferon-γ (IFN-γ) and IL-6, and ameliorated GVHD. The protective role of IL-25 was dependent on Lypd8, an antimicrobial molecule produced by enterocytes in the colon that suppresses motility of flagellated bacteria. In clinical colon biopsies, low numbers of goblet cells were significantly associated with severe intestinal GVHD, increased transplant-related mortality, and poor survival after HSCT. Goblet cell loss is associated with poor transplant outcome, and administration of IL-25 represents an adjunct therapeutic strategy for GVHD by protecting goblet cells.

Short-term treatment with imetelstat sensitizes hematopoietic malignant cells to a genotoxic agent via suppression of the telomerase-mediated DNA repair process.
Daisuke Hidaka, Masahiro Onozawa, Naohiro Miyashita, Shota Yokoyama, Masao Nakagawa, Daigo Hashimoto, Takanori Teshima
Leukemia & lymphoma, 61, 11, 1, 11, 2020年06月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Imetelstat is a specific and competitive inhibitor of telomerase enzymatic activity. We demonstrated that imetelstat could interfere with the DNA repair process and enhance the effect of DNA damaging agents using hematological tumor cell lines. Short-term administration of imetelstat enhanced growth suppression by anticancer agents and radiation. It also upregulated γH2AX expression induced by irradiation. Immunofluorescence staining showed that both human telomerase reverse transcriptase (hTERT) and γH2AX were upregulated and co-localized in the nucleus of peripheral blood mononuclear cells after irradiation, suggesting that hTERT was involved in the DNA-DSB repair process. Imetelstat enhanced growth inhibitory effect of cytotoxic agents in short-term culture without shortening of telomeres, indicating that this effect was attributed by telomere length independent mechanism. Our results suggest that the combination of short-term treatment with imetelstat and cytotoxic agent is a promising strategy to treat a wide variety of hematopoietic malignancies.

High metabolic heterogeneity on baseline 18FDG-PET/CT scan as a poor prognostic factor for newly diagnosed diffuse large B-cell lymphoma.
Hajime Senjo, Kenji Hirata, Koh Izumiyama, Koichiro Minauchi, Eriko Tsukamoto, Kazuo Itoh, Minoru Kanaya, Akio Mori, Shuichi Ota, Daigo Hashimoto, Takanori Teshima
Blood advances, 4, 10, 2286, 2296, 2020年05月26日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Metabolic heterogeneity (MH) can be measured using 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT), and it indicates an inhomogeneous tumor microenvironment. High MH has been shown to predict a worse prognosis for primary mediastinal B-cell lymphoma, whereas its prognostic value in diffuse large B-cell lymphoma (DLBCL) remains to be determined. In the current study, we investigated the prognostic values of MH evaluated in newly diagnosed DLBCL. In the training cohort, 86 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone-like chemotherapies were divided into low-MH and high-MH groups using receiver operating characteristic analysis. MH was not correlated with metabolic tumor volume of the corresponding lesion, indicating that MH was independent of tumor burden. At 5 years, overall survivals were 89.5% vs 61.2% (P = .0122) and event-free survivals were 73.1% vs 51.1% (P = .0327) in the low- and high-MH groups, respectively. A multivariate Cox-regression analysis showed that MH was an independent predictive factor for overall survival. The adverse prognostic impacts of high MH were confirmed in an independent validation cohort with 64 patients. In conclusion, MH on baseline 18FDG-PET/CT scan predicts treatment outcomes for patients with newly diagnosed DLBCL.

Histological and magnified endoscopic evaluation of villous atrophy in gastrointestinal graft-versus-host disease.
Kana Matsuda, Shoko Ono, Ikko Tanaka, Masaki Inoue, Sayoko Kinowaki, Marin Ishikawa, Momoko Tsuda, Keiko Yamamoto, Yuichi Shimizu, Shuichiro Takahashi, Eiko Hayase, Daigo Hashimoto, Takanori Teshima, Naoya Sakamoto
Annals of hematology, 99, 5, 1121, 1128, 2020年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, AIM:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease. METHODS:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated. RESULTS:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum. CONCLUSION:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicentre, single-arm, phase 2 trial.
Kazuyuki Shimada, Motoko Yamaguchi, Yoshiko Atsuta, Kosei Matsue, Keijiro Sato, Shigeru Kusumoto, Hirokazu Nagai, Jun Takizawa, Noriko Fukuhara, Koji Nagafuji, Kana Miyazaki, Eiichi Ohtsuka, Masataka Okamoto, Yasumasa Sugita, Toshiki Uchida, Satoshi Kayukawa, Atsushi Wake, Daisuke Ennishi, Yukio Kondo, Tohru Izumi, Yoshihiro Kin, Kunihiro Tsukasaki, Daigo Hashimoto, Masaaki Yuge, Atsumi Yanagisawa, Yachiyo Kuwatsuka, Satoko Shimada, Yasufumi Masaki, Nozomi Niitsu, Hitoshi Kiyoi, Ritsuro Suzuki, Takashi Tokunaga, Shigeo Nakamura, Tomohiro Kinoshita
The Lancet. Oncology, 21, 4, 593, 602, 2020年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL. METHODS: PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20-79 years, had an Eastern Cooperative Group performance status of 0-3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m2 intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1-5 of cycle one and days 2-6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m2 intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up. FINDINGS: Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5-5·5). 2-year progression-free survival was 76% (95% CI 58-87). The most frequent adverse events of grade 3-4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment. INTERPRETATION: R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation. FUNDING: The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.

Short-term KRP203 and posttransplant cyclophosphamide for graft-versus-host disease prophylaxis.
Emi Yokoyama, Daigo Hashimoto, Eiko Hayase, Takahide Ara, Reiki Ogasawara, Shuichiro Takahashi, Hiroyuki Ohigashi, Takahiro Tateno, Yuta Hasegawa, Xuanzhong Chen, Takanori Teshima
Bone marrow transplantation, 55, 4, 787, 795, 2020年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Posttransplant high-dose cyclophosphamide (PTCY) has been increasingly used as graft-versus-host disease (GVHD) prophylaxis after HLA-haploidentical or matched hematopoietic stem cell transplantation (SCT). However, PTCY alone is insufficient and requires additional immunosuppressants such as calcineurin inhibitors. In the current study, we evaluated effects of a novel GVHD prophylaxis with PTCY in combination with short-term KRP203, a selective agonist of sphingosine-1-phosphate receptor 1 that regulates egress of lymphocytes from the secondary lymphoid organs (SLOs) in mice. Short-term oral administration of KRP203 alone induced apoptosis of donor T cells in the SLOs and ameliorated GVHD. Administration of KRP203 significantly preserved graft-versus-leukemia effects compared to cyclosporin. A combination of KRP203 on days 0 to +4 and PTCY on day +3 synergistically suppressed donor T-cell migration into the intestine and skin, and ameliorated GVHD more potently than PTCY alone. A combination of short-term KRP203 and PTCY is a promising novel calcineurin-free GVHD prophylaxis in HLA-haploidentical SCT.

Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation.
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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Loss of nivolumab binding to T cell PD-1 predicts relapse of Hodgkin lymphoma.
Reiki Ogasawara, Daigo Hashimoto, Junichi Sugita, Fumihiko Yamawaki, Tomoaki Naka, Tomoko Mitsuhashi, Shuichiro Takahashi, Naohiro Miyashita, Kohei Okada, Masahiro Onozawa, Yoshihiro Matsuno, Takanori Teshima
International journal of hematology, 111, 3, 475, 479, 2020年03月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Nivolumab is effective in the treatment of classical Hodgkin lymphoma that relapsed after allogeneic hematopoietic stem cell transplantation (SCT) with the risk of graft-versus-host disease; however, the optimal time and dose of nivolumab administration remain to be investigated. Nivolumab binding to PD-1 masks flowcytometric detection of PD-1 by the anti-PD-1 monoclonal antibody EH12.1. Using this method, we monitored nivolumab binding on T cells after nivolumab treatment in a patient with classical Hodgkin lymphoma relapsed after allogeneic SCT. Nivolumab was effective while prolonged nivolumab binding was evident, but restoration of PD-1 staining predicted tumor relapse. Flowcytometric monitoring of nivolumab binding on T cells could be a promising biomarker for predicting tumor relapse and determining the timing of nivolumab administration.

Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.
Jonathan U Peled, Antonio L C Gomes, Sean M Devlin, Eric R Littmann, Ying Taur, Anthony D Sung, Daniela Weber, Daigo Hashimoto, Ann E Slingerland, John B Slingerland, Molly Maloy, Annelie G Clurman, Christoph K Stein-Thoeringer, Kate A Markey, Melissa D Docampo, Marina Burgos da Silva, Niloufer Khan, André Gessner, Julia A Messina, Kristi Romero, Meagan V Lew, Amy Bush, Lauren Bohannon, Daniel G Brereton, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Gabriel K Armijo, Yusuke Shono, Míriam Sanchez-Escamilla, Nerea Castillo Flores, Ana Alarcon Tomas, Richard J Lin, Lucrecia Yáñez San Segundo, Gunjan L Shah, Christina Cho, Michael Scordo, Ioannis Politikos, Kasumi Hayasaka, Yuta Hasegawa, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Robert R Jenq, Takanori Teshima, Nelson J Chao, Ernst Holler, Joao B Xavier, Eric G Pamer, Marcel R M van den Brink
The New England journal of medicine, 382, 9, 822, 834, 2020年02月27日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death. RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival. CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).

Salvage Transplantation with Cord Blood for Graft Rejection of Peripheral Blood Stem Cells due to Donor Specific Antibody
Maria Regina Pelobello de Leon, Shuichiro Takahashi, Masahiro Onozawa, Makoto Ito, Manabu Nakano, Hajime Senjo, Masahiro Chiba, Hiroyuki Ohigashi, Emi Yokoyama, Junichi Sugita, Daigo Hashimoto, Takanori Teshima
BLOOD CELL THERAPY / The official journal of APBMT, 3, 3, 74, 77, Asia-Pacific Blood and Marrow Transplantation Group, 2020年, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various kinds of hematological malignancies and disorders. Recently, HLA-haploidentical stem cell transplantation with post-transplantation cyclophosphamide (PTCy-haplo HSCT) has been widely performed due to its safety and favorable immune recovery. However, graft rejection remains an obstacle to PTCy-haplo HSCT. Donor specific antibody (DSA) is considered to be a major factor of graft rejection of haplo HSCT. We herein present a case of graft rejection after PTCy haplo-HSCT due to DSA induced by pretransplant platelet transfusion after donor selection. The patient was dependent on platelet transfusion and had not received cytotoxic chemotherapy because he was diagnosed as myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable. We retrospectively confirmed the level of DSA just before the first transplantation and found that it was dramatically elevated, which was enough to cause graft rejection. We successfully performed cord blood transplantation of the HLA that was not the target of DSA, as salvage transplantation without any desensitization. This case illustrates that we have to confirm the presence of DSA immediately before the haplo-HSCT, particularly in high risk patients who are dependent on platelet transfusion and have no cytotoxic chemotherapy before HSCT.

[Animal models in the study of allogeneic hematopoietic stem cell transplantation].
Daigo Hashimoto
[Rinsho ketsueki] The Japanese journal of clinical hematology, 61, 4, 369, 378, 2020年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, For the past seven decades, animal models of allogeneic hematopoietic stem cell transplantation (SCT) have contributed to the development of clinical SCT. Murine models are particularly useful to study the pathophysiology of graft-versus-host disease (GVHD) and the mechanism of graft-versus-leukemia (GVL) effects after SCT because of the variety of genetically engineered mice and numerous research reagents for immune profiling. SCT models using non-human primates are useful in preclinical studies to evaluate the efficacy and safety of novel therapies developed in murine models. In the present manuscript, the advantage and disadvantages of each animal SCT model is discussed, mainly focusing on the studies of GVHD and GVL effects.

[Graft-versus-host disease: new insights into disease pathogenesis].
Daigo Hashimoto
[Rinsho ketsueki] The Japanese journal of clinical hematology, 61, 8, 959, 964, 2020年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, Graft-versus-host disease (GVHD) is a potentially life-threatening complication associated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Although prophylaxis and GVHD treatment using immunosuppressants are essential for a successful allo-SCT, profound immunosuppression could lead to an infection and/or the recurrence of malignant diseases. Recently, the concept of tissue tolerance has emerged. This concept has been identified as a means to suppress GVHD by relying on tissue-intrinsic mechanisms that are independent from those underlying immune tolerance. Thus, GVHD prophylaxis and treatments targeting the mechanisms that promote tissue tolerance could help suppress GVHD and maintain leukocyte-mediated immune responses against tumors and infectious pathogens. Epithelial regeneration from LGR5-positive intestinal stem cells and epithelial maintenance mediated by metabolites from the intestinal microbiota are representative mechanisms that promote tissue tolerance in the gut. However, these protective mechanisms are weakened by GVHD and conditioning regimens. This review focuses on the pathophysiology of acute GVHD and tissue-intrinsic mechanisms that promote tissue tolerance.

Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease.
Satomi Matsuoka, Daigo Hashimoto, Masanori Kadowaki, Hiroyuki Ohigashi, Eiko Hayase, Emi Yokoyama, Yuta Hasegawa, Takahiro Tateno, Xuanzhong Chen, Kazutoshi Aoyama, Hideyo Oka, Masahiro Onozawa, Kiyoshi Takeda, Koichi Akashi, Takanori Teshima
Haematologica, 105, 1, 226, 234, 2020年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Myeloid differentiation factor 88 (MyD88) signaling has a crucial role in activation of both innate and adoptive immunity. MyD88 transduces signals via Toll-like receptor and interleukin-1 receptor superfamily to the NFκB pathway and inflammasome by forming a molecular complex with interleukin-1 receptor-associated kinase 4. The MyD88/interleukin-1 receptor-associated kinase 4 pathway plays an important role, not only in innate immunity, but also T-cell immunity; however, its role in donor T cells on the pathophysiology of graft-versus-host disease (GvHD) remains to be elucidated. We addressed this issue by using MyD88-deficient T cells in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-SCT). While MyD88-deficient and wild-type T cells proliferated equivalently after transplantation, MyD88-deficient T cells demonstrated impaired survival and differentiation toward Th1, Tc1, and Th17, and induced less severe GvHD compared to wild-type T cells. Administration of interleukin-1 receptor-associated kinase 4 inhibitor PF-06650833 significantly ameliorated GvHD after allo-SCT. These results thus demonstrate that donor T-cell MyD88/interleukin-1 receptor-associated kinase 4 pathway is a novel therapeutic target against GvHD after allo-SCT.

Lactose drives Enterococcus expansion to promote graft-versus-host disease.
C K Stein-Thoeringer, K B Nichols, A Lazrak, M D Docampo, A E Slingerland, J B Slingerland, A G Clurman, G Armijo, A L C Gomes, Y Shono, A Staffas, M Burgos da Silva, S M Devlin, K A Markey, D Bajic, R Pinedo, A Tsakmaklis, E R Littmann, A Pastore, Y Taur, S Monette, M E Arcila, A J Pickard, M Maloy, R J Wright, L A Amoretti, E Fontana, D Pham, M A Jamal, D Weber, A D Sung, D Hashimoto, C Scheid, J B Xavier, J A Messina, K Romero, M Lew, A Bush, L Bohannon, K Hayasaka, Y Hasegawa, M J G T Vehreschild, J R Cross, D M Ponce, M A Perales, S A Giralt, R R Jenq, T Teshima, E Holler, N J Chao, E G Pamer, J U Peled, M R M van den Brink
Science (New York, N.Y.), 366, 6469, 1143, 1149, 2019年11月29日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Unusual computed tomography findings of acute eosinophilic pneumonia after cord blood transplantation.
Hajime Senjo, Daigo Hashimoto
International journal of hematology, 110, 4, 387, 388, 2019年10月, ［査読有り］, ［国内誌］
英語

Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial.
Kenichi Yamahara, Akiko Hamada, Toshihiro Soma, Rika Okamoto, Masaya Okada, Satoshi Yoshihara, Kyoko Yoshihara, Kazuhiro Ikegame, Hiroya Tamaki, Katsuji Kaida, Takayuki Inoue, Yuko Ohsugi, Hiroki Nishikawa, Hiroshi Hayashi, Yoichi M Ito, Hiroaki Iijima, Shunsuke Ohnishi, Daigo Hashimoto, Toshiyuki Isoe, Takanori Teshima, Hiroyasu Ogawa, Norihiro Sato, Yoshihiro Fujimori
BMJ open, 9, 7, e026403, 2019年07月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD. METHODS AND ANALYSIS: This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01. ETHICS AND DISSEMINATION: The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000029945.

Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD.
Hiroyuki Ohigashi, Daigo Hashimoto, Eiko Hayase, Shuichiro Takahashi, Takahide Ara, Tomohiro Yamakawa, Junichi Sugita, Masahiro Onozawa, Masao Nakagawa, Takanori Teshima
Blood advances, 3, 7, 1003, 1010, 2019年04月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A-coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.

生物由来原料基準を満たす国産ウシ血小板溶解物「NeoSERA」を原材料とする羊膜由来間葉系幹細胞の細胞製剤化
山原 研一, 浜田 彰子, 黒田 将子, 池本 純子, 吉原 享子, 吉原 哲, 岡田 昌也, 橋本 大吾, 相馬 俊裕, 豊嶋 崇徳, 藤盛 好啓
日本輸血細胞治療学会誌, 65, 2, 476, 476, (一社)日本輸血・細胞治療学会, 2019年04月
日本語

Serum level of soluble interleukin-2 receptor is positively correlated with metabolic tumor volume on 18 F-FDG PET/CT in newly diagnosed patients with diffuse large B-cell lymphoma.
Hajime Senjo, Minoru Kanaya, Koh Izumiyama, Koichiro Minauchi, Kenji Hirata, Akio Mori, Makoto Saito, Masanori Tanaka, Hiroaki Iijima, Eriko Tsukamoto, Kazuo Itoh, Shuichi Ota, Masanobu Morioka, Daigo Hashimoto, Takanori Teshima
Cancer medicine, 8, 3, 953, 962, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using 18 F-FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18 F-FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin-2 receptor (sIL-2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL-2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ≥150 cm3 or sIL-2R ≥ 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ≥150 cm3 and sIL-2R ≥1300 U/mL was significantly associated with worse 5-year overall survival and event-free survival. Importantly, each of sIL-2R <1300 U/mL or TMTV <150 cm3 identified patients with favorable prognosis among NCCN-IPI high-intermediate and high-risk group. Serum level of sIL-2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by 18 F-FDG PET/CT that can predict treatment outcomes of patients with DLBCL.

UTILITY OF LISS AS AN AUTOANTIBODY ADSORPTION METHOD FOR DETECTION OF COEXISTING ALLOANTIBODIES IN PATIENTS WITH AUTOANTIBODIES
Takayo Uwatoko, Chiaki Watanabe, Makoto Ito, Ryo Uozumi, Yasuhiro Hayashi, Shuichiro Takahashi, Naohiro Miyashita, Souichi Shiratori, Daigo Hashimoto, Junichi Sugita, Eiko Hayase, Koji Akizawa, Takanori Teshima
Japanese Journal of Transfusion and Cell Therapy, 65, 1, 98, 102, Japan Society of Transfusion Medicine and Cell Therapy, 2019年02月28日
研究論文（学術雑誌）

自己抗体保有患者の同種抗体検出におけるLISSを用いた自己抗体吸着法の有用性の検討
上床 貴代, 渡邊 千秋, 伊藤 誠, 魚住 諒, 林 泰弘, 高橋 秀一郎, 宮下 直洋, 白鳥 聡一, 橋本 大吾, 杉田 純一, 早瀬 英子, 秋沢 宏次, 豊嶋 崇徳
日本輸血細胞治療学会誌, 65, 1, 98, 102, (一社)日本輸血・細胞治療学会, 2019年02月
日本語

ニッチ機能による組織常在マクロファージの分化と機能の制御　　　　　　　　　　　　　　　
橋本 大吾
臨床血液, 59, 10, 1886, 1894, 2018年10月, ［査読有り］, ［招待有り］, ［筆頭著者］
日本語, 研究論文（学術雑誌）

Essential role of IFN-γ in T cell–associated intestinal inflammation
Yoshihiro Eriguchi, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuichiro Takahashi, Daigo Hashimoto, Takanori Teshima, Tokiyoshi Ayabe, Michael E. Selsted, André J. Ouellette
JCI Insight, 3, 18, American Society for Clinical Investigation, 2018年09月20日, ［査読有り］
研究論文（学術雑誌）

成人急性リンパ性白血病におけるIKZF1欠失およびCRLF2発現の解析(Analysis of IKZF1 deletion and CRLF2 expression in adult patients with acute lymphoblastic leukemia)　　　　　　　　　　　　　　　
橋口 淳一, 小野澤 真弘, 藤澤 真一, 高橋 秀一郎, 宮下 直洋, 早瀬 英子, 白鳥 聡一, 後藤 秀樹, 杉田 純一, 中川 雅夫, 橋本 大吾, 加畑 馨, 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, 宮城島 拓人, 柿木 康孝, 黒澤 光俊, 岩崎 博, 近藤 健, 豊嶋 崇徳
臨床血液, 59, 9, 1648, 1648, (一社)日本血液学会-東京事務局, 2018年09月
英語

Disseminated fusariosis emerged from prolonged local genital infection after cord blood transplantation
Kohei Okada, Tomoyuki Endo, Daigo Hashimoto, Tomoyuki Saga, Takahide Ara, Reiki Ogasawara, Atsushi Yasumoto, Makoto Ibata, Mutsumi Takahata, Akio Shigematsu, Takeshi Kondo, Yasunori Muraosa, Toshifumi Nomura, Hiromi Kanno-Okada, Satoshi Hashino, Shinya Tanaka, Katsuhiko Kamei, Takanori Teshima
Journal of Infection and Chemotherapy, 24, 8, 660, 663, Elsevier B.V., 2018年08月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia
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, Elsevier B.V., 2018年07月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Intestinal Lymphatic Endothelial Cells Produce R-Spondin3.
Ogasawara R, Hashimoto D, Kimura S, Hayase E, Ara T, Takahashi S, Ohigashi H, Yoshioka K, Tateno T, Yokoyama E, Ebata K, Kondo T, Sugita J, Onozawa M, Iwanaga T, Teshima T
Scientific reports, 8, 1, 10719, 10719, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The R-Spondin (R-Spo) family regulates WNT signaling and stimulates the proliferation and differentiation of intestinal stem cells (ISCs). R-Spo plays a critical role in maintaining intestinal homeostasis, but endogenous producers of R-Spo in the intestine remain to be investigated. We found that R-Spo3 was the major R-Spo family member produced in the intestine and it was predominantly produced by CD45-CD90+CD31+ lymphatic endothelial cells (LECs) in the lamina propria of the intestinal mucosa. Transcriptome analysis demonstrated that LECs highly expressed R-Spo receptor, Lgr5, suggesting an autocrine stimulatory loop in LECs. LECs were significantly reduced in number, and their R-Spo3 production was impaired in intestinal graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. The impaired production of R-Spo3 in the intestine may be a novel mechanism of delayed tissue repair and defective mucosal defense in intestinal GVHD. We demonstrate a novel role of intestinal LECs in producing R-Spondin3 to maintain intestinal homeostasis.

The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation.
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07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia: A Hokkaido Leukemia Net Study.
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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

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, (一社)日本血液学会-東京事務局, 2018年07月
日本語

Hematogones Predict Better Outcome in Allogeneic Hematopoietic Stem Cell Transplantation Irrespective of Graft Sources.
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, Elsevier BV, 2018年06月, ［査読有り］
研究論文（学術雑誌）

Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease
Shuichiro Takahashi, Daigo Hashimoto, Eiko Hayase, Reiki Ogasawara, Hiroyuki Ohigashi, Takahide Ara, Emi Yokoyama, Ko Ebata, Satomi Matsuoka, Geoffrey R. Hill, Junichi Sugita, Masahiro Onozawa, Takanori Teshima
Blood, 131, 18, 2074, 2085, American Society of Hematology, 2018年05月03日, ［査読有り］
英語, 研究論文（学術雑誌）

Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Kana Matsuda, Shoko Ono, Marin Ishikawa, Shuichi Miyamoto, Satoshi Abiko, Momoko Tsuda, Keiko Yamamoto, Takahiko Kudo, Yuichi Shimizu, Eiko Hayase, Daigo Hashimoto, Takanori Teshima, Yoshihiro Matsuno, Naoya Sakamoto
Annals of Hematology, 97, 5, 877, 883, Springer Verlag, 2018年05月01日, ［査読有り］
英語, 研究論文（学術雑誌）

A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.
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, Springer Verlag, 2018年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Vitamin A–coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease
Tomohiro Yamakawa, Hiroyuki Ohigashi, Daigo Hashimoto, Eiko Hayase, Shuichiro Takahashi, Miyono Miyazaki, Kenjiro Minomi, Masahiro Onozawa, Yoshiro Niitsu, Takanori Teshima
Blood, 131, 13, 1476, 1485, American Society of Hematology, 2018年03月29日, ［査読有り］
英語, 研究論文（学術雑誌）

T-cell depletion effects of low-dose antithymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell 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, 2018年02月, ［査読有り］, ［国際誌］
英語

脳死肝移植時のフィブリノゲン製剤使用による術中出血量と輸血使用量に関する検討
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
日本語

R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease
Eiko Hayase, Daigo Hashimoto, Kiminori Nakamura, Clara Noizat, Reiki Ogasawara, Shuichiro Takahashi, Hiroyuki Ohigashi, Yuki Yokoi, Rina Sugimoto, Satomi Matsuoka, Takahide Ara, Emi Yokoyama, Tomohiro Yamakawa, Ko Ebata, Takeshi Kondo, Rina Hiramine, Tomoyasu Aizawa, Yoshitoshi Ogura, Tetsuya Hayashi, Hiroshi Mori, Ken Kurokawa, Kazuma Tomizuka, Tokiyoshi Ayabe, Takanori Teshima
JOURNAL OF EXPERIMENTAL MEDICINE, 214, 12, 3507, 3518, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）

同種造血幹細胞移植を施行したCSF3R T613I変異陽性非定型慢性骨髄性白血病　　　　　　　　　　　　　　　
原田 晋平, 岡田 耕平, 日高 大輔, 早瀬 英子, 後藤 秀樹, 橋本 大吾, 加畑 馨, 遠藤 知之, 豊嶋 崇徳
臨床血液, 58, 11, 2299, 2299, (一社)日本血液学会-東京事務局, 2017年11月
日本語

Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images
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］
英語, 研究論文（学術雑誌）

Diffuse large B-cell lymphoma with a bulky mass in the cranial vault
Minoru Kanaya, Tomoyuki Endo, Daigo Hashimoto, Shogo Endo, Ryo Takemura, Kohei Okada, Kanako C. Hatanaka, Yoshihiro Matsuno, Takanori Teshima
INTERNATIONAL JOURNAL OF HEMATOLOGY, 106, 2, 147, 148, 2017年08月
英語

Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation
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
英語, 研究論文（学術雑誌）

MALDI-TOF MS in post-transplant bloodstream infections: reliable identification of causative bacteria in the neutropenic phase
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
英語

Graft-versus-host disease targets ovary and causes female infertility in mice
Sonoko Shimoji, Daigo Hashimoto, Hidetsugu Tsujigiwa, Kohta Miyawaki, Koji Kato, Shuichiro Takahashi, Reiki Ogasawara, Takashi Jiromaru, Hiromi Iwasaki, Toshihiro Miyamoto, Koichi Akashi, Takanori Teshima
BLOOD, 129, 9, 1216, 1225, 2017年03月
英語, 研究論文（学術雑誌）

Leukemogenic kinase FIP1L1-PDGFRA and a small ubiquitin-like modifier E3 ligase, PIAS1, form a positive cross-talk through their enzymatic activities
Makoto Ibata, Junko Iwasaki, Yoichiro Fujioka, Koji Nakagawa, Stephanie Darmanin, Masahiro Onozawa, Daigo Hashimoto, Yusuke Ohba, Shigetsugu Hatakeyama, Takanori Teshima, Takeshi Kondo
CANCER SCIENCE, 108, 2, 200, 207, 2017年02月
英語, 研究論文（学術雑誌）

Graft-versus-host disease in the ovary potentially causes female infertility after allogeneic hematopoietic stem cell transplantation.
Shimoji S, Hashimoto D, Teshima T
[Rinsho ketsueki] The Japanese journal of clinical hematology, 58, 7, 827, 834, 2017年, ［査読有り］

Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD
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
英語, 研究論文（学術雑誌）

The Mononuclear Phagocyte System in Organ Transplantation
J. Ochando, W. -H. Kwan, F. Ginhoux, J. A. Hutchinson, D. Hashimoto, M. Collin
AMERICAN JOURNAL OF TRANSPLANTATION, 16, 4, 1053, 1069, 2016年04月
英語

Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition
Helene Salmon, Juliana Idoyaga, Adeeb Rahman, Marylene Leboeuf, Romain Remark, Stefan Jordan, Maria Casanova-Acebes, Makhzuna Khudoynazarova, Judith Agudo, Navpreet Tung, Svetoslav Chakarov, Christina Rivera, Brandon Hogstad, Marcus Bosenberg, Daigo Hashimoto, Sacha Gnjatic, Nina Bhardwaj, Anna Karolina Palucka, Brian D. Brown, Joshua Brody, Florent Ginhoux, Miriam Merad
IMMUNITY, 44, 4, 924, 938, 2016年04月
英語, 研究論文（学術雑誌）

Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome
Souichi Shiratori, Katsuya Fujimoto, Machiko Nishimura, Kanako C. Hatanaka, Mizuha Kosugi-Kanaya, Kohei Okada, Junichi Sugita, Akio Shigematsu, Daigo Hashimoto, Tomoyuki Endo, Takeshi Kondo, Riichiro Abe, Satoshi Hashino, Yoshihiro Matsuno, Hiroshi Shimizu, Takanori Teshima
HEMATOLOGICAL ONCOLOGY, 34, 1, 9, 16, 2016年03月
英語, 研究論文（学術雑誌）

Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different Responses to Chemotherapy
Kohei Kasahara, Masahiro Onozawa, Naohiro Miyashita, Emi Yokohata, Miho Yoshida, Minoru Kanaya, Mizuha Kosugi-Kanaya, Ryo Takemura, Shojiro Takahashi, Junichi Sugita, Akio Shigematsu, Mutsumi Takahata, Shinichi Fujisawa, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Takanori Teshima
Case Reports in Hematology, 2016, 1, 5, Hindawi Limited, 2016年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We report a case of acute myeloid leukemia (AML) with two cytogenetically unrelated clones. The patient was a 45-year-old male who was diagnosed with acute monoblastic leukemia (AMoL). Initial G-band analysis showed 51,XY,+6,+8,inv(9)(p12q13)c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis after induction therapy showed 45,XY,-7,inv(9)(p12q13)c[19]/46,XY,inv(9)(p12q13)c[1]. Retrospective FISH analysis revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with multiple trisomies was eliminated after induction therapy and never recurred, but a clone with monosomy 7 was still detected in myelodysplastic marrow with a normal blast percentage. Both clones were successfully eliminated after related peripheral blood stem cell transplantation, but the patient died of relapsed AML with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6, 8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) with chromosome 7 monosomy showing different responses to chemotherapy. Simultaneous onset of cytogenetically unrelated hematological malignancies that each have a different disease status is a rare phenomenon but is important to diagnose for a correct understanding of the disease status and for establishing an appropriate treatment strategy.

Decreased secretion of Paneth cell α-defensins in graft-versus-host disease
Y. Eriguchi, K. Nakamura, D. Hashimoto, S. Shimoda, N. Shimono, K. Akashi, T. Ayabe, T. Teshima
Transplant Infectious Disease, 17, 5, 702, 706, 2015年10月
英語, 研究論文（学術雑誌）

Key players in intestinal GVHD
Daigo Hashimoto, Takanori Teshima
[Rinshō ketsueki] The Japanese journal of clinical hematology, 56, 807, 814, 2015年07月01日

α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice
Hidetaka Uryu, Hidetaka Uryu, Daigo Hashimoto, Koji Kato, Eiko Hayase, Satomi Matsuoka, Reiki Ogasawara, Shuichiro Takahashi, Yoshinobu Maeda, Hiromi Iwasaki, Toshihiro Miyamoto, Shinobu Saijo, Yoichiro Iwakura, Geoffrey R. Hill, Koichi Akashi, Koichi Akashi, Takanori Teshima
Blood, 125, 19, 3014, 3023, 2015年05月
英語, 研究論文（学術雑誌）

Requirement for Innate Immunity and CD90(+)NK1.1(-) Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy
Marina Moskalenko, Michael Pan, Yichun Fu, Ellen H. de Moll, Daigo Hashimoto, Arthur Mortha, Marylene Leboeuf, Padmini Jayaraman, Sebastian Bernardo, Andrew G. Sikora, Jedd Wolchok, Nina Bhardwaj, Miriam Merad, Yvonne Saenger
CANCER IMMUNOLOGY RESEARCH, 3, 3, 296, 304, 2015年03月
英語, 研究論文（学術雑誌）

FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia
Junko Iwasaki, Takeshi Kondo, Stephanie Darmanin, Makoto Ibata, Masahiro Onozawa, Daigo Hashimoto, Naoya Sakamoto, Takanori Teshima
ANNALS OF HEMATOLOGY, 93, 9, 1473, 1481, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Erratum: Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility (Cell (2014) 158 (300â€"313) )
Paul Andrew Muller, Balázs Koscsó, Gaurav Manohar Rajani, Korey Stevanovic, Marie Luise Berres, Daigo Hashimoto, Arthur Mortha, Marylene Leboeuf, Xiu Min Li, Daniel Mucida, E. Richard Stanley, Stephanie Dahan, Kara Gross Margolis, Michael David Gershon, Miriam Merad, Milena Bogunovic
Cell, 158, 1210, 2014年08月28日

Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility
Paul Andrew Muller, Balazs Koscso, Gaurav Manohar Rajani, Korey Stevanovic, Marie-Luise Berres, Daigo Hashimoto, Arthur Mortha, Marylene Leboeuf, Xiu-Min Li, Daniel Mucida, E. Richard Stanley, Stephanie Dahan, Kara Gross Margolis, Michael David Gershon, Miriam Merad, Milena Bogunovic
CELL, 158, 2, 300, 313, 2014年07月
英語, 研究論文（学術雑誌）

Stenotrophomonas maltophilia infection during allogeneic hematopoietic stem cell transplantation: a single-center experience
Souichi Shiratori, Kentaro Wakasa, Kohei Okada, Junichi Sugita, Koji Akizawa, Akio Shigematsu, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Chikara Shimizu, Satoshi Hashino, Takanori Teshima
CLINICAL TRANSPLANTATION, 28, 6, 656, 661, 2014年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation
Yusuke Shono, Souichi Shiratori, Mizuha Kosugi-Kanaya, Satoshi Ueha, Junichi Sugita, Akio Shigematsu, Takeshi Kondo, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Mitsufumi Nishio, Satoshi Hashino, Yoshihiro Matsuno, Kouji Matsushima, Junji Tanaka, Masahiro Imamura, Takanori Teshima
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 20, 4, 495, 500, 2014年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Central Role of Conventional Dendritic Cells in Regulation of Bone Marrow Release and Survival of Neutrophils
Jingjing Jiao, Ana-Cristina Dragomir, Peri Kocabayoglu, Adeeb H. Rahman, Andrew Chow, Daigo Hashimoto, Marylene Leboeuf, Thomas Kraus, Thomas Moran, Gonzalo Carrasco-Avino, Scott L. Friedman, Miriam Merad, Costica Aloman
JOURNAL OF IMMUNOLOGY, 192, 7, 3374, 3382, 2014年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice
Gerold Bongers, Michelle E. Pacer, Thais H. Geraldino, Lili Chen, Zhengxiang He, Daigo Hashimoto, Glaucia C. Furtado, Jordi Ochando, Kevin A. Kelley, Jose C. Clemente, Miriam Merad, Harm van Bakel, Sergio A. Lira
JOURNAL OF EXPERIMENTAL MEDICINE, 211, 3, 457, 472, 2014年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis
Arthur Mortha, Aleksey Chudnovskiy, Daigo Hashimoto, Milena Bogunovic, Sean P. Spencer, Yasmine Belkaid, Miriam Merad
SCIENCE, 343, 6178, 1477, +, 2014年03月, ［査読有り］
英語, 研究論文（学術雑誌）

造血幹細胞移植後GVHDと消化管傷害　　　　　　　　　　　　　　　
早瀬英子, 橋本大吾, 豊嶋崇徳
最新医学, 69, 3, 503, 507, 2014年03月

The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids
Judith Agudo, Albert Ruzo, Navpreet Tung, Helene Salmon, Marylene Leboeuf, Daigo Hashimoto, Christian Becker, Lee-Ann Garrett-Sinha, Alessia Baccarini, Miriam Merad, Brian D. Brown
NATURE IMMUNOLOGY, 15, 1, 54, 62, 2014年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning
M. Koyama, D. Hashimoto, K. Nagafuji, T. Eto, Y. Ohno, K. Aoyama, H. Iwasaki, T. Miyamoto, G. R. Hill, K. Akashi, T. Teshima
BONE MARROW TRANSPLANTATION, 49, 1, 110, 115, 2014年01月
英語, 研究論文（学術雑誌）

Reciprocal Expression of Enteric Antimicrobial Proteins in Intestinal Graft-Versus-Host Disease
Yoshihiro Eriguchi, Hidetaka Uryu, Kiminori Nakamura, Sonoko Shimoji, Shuichiro Takashima, Hiromi Iwasaki, Toshihiro Miyamoto, Nobuyuki Shimono, Daigo Hashimoto, Koichi Akashi, Tokiyoshi Ayabe, Takanori Teshima
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 19, 10, 1525, 1529, 2013年10月, ［査読有り］
英語, 研究論文（学術雑誌）

血球トラフィッキングとGVHD　　　　　　　　　　　　　　　
橋本大吾, 豊嶋崇徳
血液フロンティア, 23, 10, 59, 70, 2013年10月

CD169(+) macrophages provide a niche promoting erythropoiesis under homeostasis and stress
Andrew Chow, Matthew Huggins, Jalal Ahmed, Daigo Hashimoto, Daniel Lucas, Yuya Kunisaki, Sandra Pinho, Marylene Leboeuf, Clara Noizat, Nico van Rooijen, Masato Tanaka, Zhizhuang Joe Zhao, Aviv Bergman, Miriam Merad, Paul S. Frenette
NATURE MEDICINE, 19, 4, 429, +, 2013年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Tissue-Resident Macrophages Self-Maintain Locally throughout Adult Life with Minimal Contribution from Circulating Monocytes
Daigo Hashimoto, Andrew Chow, Clara Noizat, Pearline Teo, Mary Beth Beasley, Marylene Leboeuf, Christian D. Becker, Peter See, Jeremy Price, Daniel Lucas, Melanie Greter, Arthur Mortha, Scott W. Boyer, E. Camilla Forsberg, Masato Tanaka, Nico van Rooijen, Adolfo Garcia-Sastre, E. Richard Stanley, Florent Ginhoux, Paul S. Frenette, Miriam Merad
IMMUNITY, 38, 4, 792, 804, 2013年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Cross-presenting CD103(+) dendritic cells are protected from influenza virus infection
Julie Helft, Balaji Manicassamy, Pierre Guermonprez, Daigo Hashimoto, Aymeric Silvin, Judith Agudo, Brian D. Brown, Mirco Schmolke, Jennifer C. Miller, Marylene Leboeuf, Kenneth M. Murphy, Adolfo Garcia-Sastre, Miriam Merad
JOURNAL OF CLINICAL INVESTIGATION, 122, 11, 4037, 4047, 2012年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Cross-presenting CD103(+) dendritic cells are protected from influenza virus infection
Julie Helft, Balaji Manicassamy, Pierre Guermonprez, Daigo Hashimoto, Aymeric Silvin, Judith Agudo, Brian D. Brown, Mirco Schmolke, Jennifer C. Miller, Marylene Leboeuf, Kenneth M. Murphy, Adolfo Garcia-Sastre, Miriam Merad
JOURNAL OF CLINICAL INVESTIGATION, 122, 11, 4037, 4047, 2012年11月
英語, 研究論文（学術雑誌）

Deciphering the transcriptional network of the dendritic cell lineage
Jennifer C. Miller, Brian D. Brown, Tal Shay, Emmanuel L. Gautier, Vladimir Jojic, Ariella Cohain, Gaurav Pandey, Marylene Leboeuf, Kutlu G. Elpek, Julie Helft, Daigo Hashimoto, Andrew Chow, Jeremy Price, Melanie Greter, Milena Bogunovic, Angelique Bellemare-Pelletier, Paul S. Frenette, Gwendalyn J. Randolph, Shannon J. Turley, Miriam Merad
NATURE IMMUNOLOGY, 13, 9, 888, 899, 2012年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Adrenergic Nerves Govern Circadian Leukocyte Recruitment to Tissues
Christoph Scheiermann, Yuya Kunisaki, Daniel Lucas, Andrew Chow, Jung-Eun Jang, Dachuan Zhang, Daigo Hashimoto, Miriam Merad, Paul S. Frenette
IMMUNITY, 37, 2, 290, 301, 2012年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Antigen-presenting cell-derived complement modulates graft-versus-host disease
Wing-Hong Kwan, Daigo Hashimoto, Estela Paz-Artal, Katya Ostrow, Melanie Greter, Hugo Raedler, M. Edward Medof, Miriam Merad, Peter S. Heeger
JOURNAL OF CLINICAL INVESTIGATION, 122, 6, 2234, 2238, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）

GM-CSF Controls Nonlymphoid Tissue Dendritic Cell Homeostasis but Is Dispensable for the Differentiation of Inflammatory Dendritic Cells
Melanie Greter, Julie Helft, Andrew Chow, Daigo Hashimoto, Arthur Mortha, Judith Agudo-Cantero, Milena Bogunovic, Emmanuel L. Gautier, Jennifer Miller, Marylene Leboeuf, Geming Lu, Costica Aloman, Brian D. Brown, Jeffrey W. Pollard, Huabao Xiong, Gwendalyn J. Randolph, Jerry E. Chipuk, Paul S. Frenette, Miriam Merad
IMMUNITY, 36, 6, 1031, 1046, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）

同種抗原による移植片対白血病効果減弱のメカニズム
朝倉 昇司, 橋本 大吾, 高嶋 秀一郎, 杉山 暖子, 前田 嘉信, 赤司 浩一, 谷本 光音, 豊嶋 崇徳
岡山医学会雑誌, 124, 1, 5, 8, 岡山医学会, 2012年04月
日本語

R-Ras is required for murine dendritic cell maturation and CD4(+) T-cell priming
Gobind Singh, Daigo Hashimoto, Xiaocai Yan, Julie Helft, Patricia J-Y Park, Ge Ma, Rui F. Qiao, Colin R. Kennedy, Shu-Hsia Chen, Miriam Merad, Andrew M. Chan
BLOOD, 119, 7, 1693, 1701, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Dendritic Cell and Macrophage Heterogeneity In Vivo
Daigo Hashimoto, Jennifer Miller, Miriam Merad
IMMUNITY, 35, 3, 323, 335, 2011年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation
Daigo Hashimoto, Andrew Chow, Melanie Greter, Yvonne Saenger, Wing-Hong Kwan, Marylene Leboeuf, Florent Ginhoux, Jordi C. Ochando, Yuya Kunisaki, Nico van Rooijen, Chen Liu, Takanori Teshima, Peter S. Heeger, E. Richard Stanley, Paul S. Frenette, Miriam Merad
JOURNAL OF EXPERIMENTAL MEDICINE, 208, 5, 1069, 1082, 2011年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Bone marrow CD169(+) macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
Andrew Chow, Daniel Lucas, Andres Hidalgo, Simon Mendez-Ferrer, Daigo Hashimoto, Christoph Scheiermann, Michela Battista, Marylene Leboeuf, Colette Prophete, Nico van Rooijen, Masato Tanaka, Miriam Merad, Paul S. Frenette
JOURNAL OF EXPERIMENTAL MEDICINE, 208, 2, 261, 271, 2011年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Harnessing dendritic cells to improve allogeneic hematopoietic cell transplantation outcome
Daigo Hashimoto, Miriam Merad
SEMINARS IN IMMUNOLOGY, 23, 1, 50, 57, 2011年02月, ［査読有り］
英語

Bone marrow CD169(+) macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
Andrew Chow, Daniel Lucas, Andres Hidalgo, Simon Mendez-Ferrer, Daigo Hashimoto, Christoph Scheiermann, Michela Battista, Marylene Leboeuf, Colette Prophete, Nico van Rooijen, Masato Tanaka, Miriam Merad, Paul S. Frenette
JOURNAL OF EXPERIMENTAL MEDICINE, 208, 2, 261, 271, 2011年02月
英語, 研究論文（学術雑誌）

Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice
Shoji Asakura, Daigo Hashimoto, Shuichiro Takashima, Haruko Sugiyama, Yoshinobu Maeda, Koichi Akashi, Mitsune Tanimoto, Takanori Teshima
JOURNAL OF CLINICAL INVESTIGATION, 120, 7, 2370, 2378, 2010年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice
Mercedes Rodriguez Garcia, Levi Ledgerwood, Yu Yang, Jiangnan Xu, Girdhari Lal, Bryna Burrell, Ge Ma, Daigo Hashimoto, Yansui Li, Peter Boros, Marcos Grisotto, Nico van Rooijen, Rafael Matesanz, Frank Tacke, Florent Ginhoux, Yaozhong Ding, Shu-Hsia Chen, Gwendalyn Randolph, Miriam Merad, Jonathan S. Bromberg, Jordi C. Ochando
JOURNAL OF CLINICAL INVESTIGATION, 120, 7, 2486, 2496, 2010年07月, ［査読有り］
英語, 研究論文（学術雑誌）

The origin and development of nonlymphoid tissue CD103(+) DCs
Florent Ginhoux, Kang Liu, Julie Helft, Milena Bogunovic, Melanie Greter, Daigo Hashimoto, Jeremy Price, Na Yin, Jonathan Bromberg, Sergio A. Lira, E. Richard Stanley, Michel Nussenzweig, Miriam Merad
JOURNAL OF EXPERIMENTAL MEDICINE, 206, 13, 3115, 3130, 2009年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Origin of the Lamina Propria Dendritic Cell Network
Milena Bogunovic, Florent Ginhoux, Julie Helft, Limin Shang, Daigo Hashimoto, Melanie Greter, Kang Liu, Claudia Jakubzick, Molly A. Ingersoll, Marylene Leboeuf, E. Richard Stanley, Michel Nussenzweig, Sergio A. Lira, Gwendalyn J. Randolph, Miriam Merad
IMMUNITY, 31, 3, 513, 525, 2009年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Improved outcome of allogeneic bone marrow transplantation due to breastfeeding-induced tolerance to maternal antigens
Kazutoshi Aoyama, Motoko Koyama, Ken-ichi Matsuoka, Daigo Hashimoto, Tatsuo Ichinohe, Mine Harada, Koichi Akashi, Mitsune Tanimoto, Takanori Teshima
BLOOD, 113, 8, 1829, 1833, 2009年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells
Motoko Koyama, Daigo Hashimoto, Kazutoshi Aoyama, Ken-ichi Matsuoka, Kennosuke Karube, Hiroaki Niiro, Mine Harada, Mitsune Tanimoto, Koichi Akashi, Takanori Teshima
BLOOD, 113, 9, 2088, 2095, 2009年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Sentiment sentence extraction using a hierarchical directed acyclic graph structure and a bootstrap approach
Kazutaka Shimada, Daigo Hashimoto, Tsutomu Endo
Proceedings of the 22nd Pacific Asia Conference on Language, Information and Computation, PACLIC 22, 341, 349, 2008年12月01日

ドナーT細胞のToll-like Receptor(TLR)シグナルはGVHDの重症化に関与する　　　　　　　　　　　　　　　
青山 一利, 小山 幹子, 橋本 大吾, 佐古田 幸美, 竹田 潔, 赤司 浩一, 原田 実根, 谷本 光音, 豊嶋 崇徳
臨床血液, 49, 9, 891, 891, (一社)日本血液学会-東京事務局, 2008年09月
日本語

母子間免疫寛容理論に基づく同種造血幹細胞移植
松岡 賢市, 青山 一利, 小山 幹子, 橋本 大吾, 朝倉 昇司, 一戸 辰夫, 谷本 光音, 豊嶋 崇徳
岡山醫學會雜誌, 120, 1, 23, 28, 岡山医学会, 2008年05月01日
日本語

Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease
Yukimi Sakoda, Daigo Hashimoto, Shoji Asakura, Kengo Takeuchi, Mine Harada, Mitsune Tanimoto, Takanori Teshima
BLOOD, 109, 4, 1756, 1764, 2007年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease
Yoshinobu Maeda, Isao Tawara, Takanori Teshima, Chen Liu, Daigo Hashimoto, Ken-ichi Matsuoka, Mitsune Tanimoto, Pavan Reddy
EXPERIMENTAL HEMATOLOGY, 35, 2, 274, 286, 2007年02月, ［査読有り］
英語, 研究論文（学術雑誌）

ドナー造血幹細胞由来細胞が慢性graft-versus-host disease(GVHD)を起こす　　　　　　　　　　　　　　　
佐古田 幸美, 橋本 大吾, 朝倉 昇司, 竹内 賢吾, 原田 実根, 谷本 光音, 豊嶋 崇徳
日本内科学会雑誌, 96, Suppl., 156, 156, (一社)日本内科学会, 2007年02月
日本語

FTY720 enhances the activation-induced apoptosis of donor T cells and modulates graft-versus-host disease
Daigo Hashimoto, Shoji Asakura, Ken-ichi Matsuoka, Yukimi Sakoda, Motoko Koyama, Kazutoshi Aoyama, Mitsune Tanimoto, Takanori Teshima
EUROPEAN JOURNAL OF IMMUNOLOGY, 37, 1, 271, 281, 2007年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Breast-feeding mediates feto-maternal tolerance and improves outcome of allogeneic bone marrow transplantation
Aoyama, Kazutoshi, Matsuoka, Ken-ichi, Hashimoto, Daigo, Ichinohe, Tatsuo, Harada, Mine, Tanimoto, Mitsune, Teshima, Takanori
BLOOD, 110, 11, 644A, 644A, 2007年
研究論文（学術雑誌）

血液型不適合移植での COBE Spectra を用いた骨髄濃縮法の検討
平安山 知子, 宮本 敏浩, 和泉 賢一, 沼田 晃彦, 亀崎 健次郎, 山崎 聡, 清島 久美, 宮本 京子, 橋本 大吾, 岩崎 潤子, 岩崎 浩己, 長藤 宏司, 原田 実根, 稲葉 頌一, 豊嶋 崇徳, 赤司 浩一
日本輸血細胞治療学会誌, 52, 6, 693, 697, The Japan Society of Transfusion Medicine and Cell Therapy, 2006年12月20日
日本語, 血液型不適合骨髄移植を行う際は, 輸注に伴う有害事象を避けるため, 骨髄液中の赤血球・血漿除去が必要である. 今回われわれは, 血液成分分離装置COBE Spectra により, 骨髄液から単核球を分離することで, 骨髄細胞濃縮を行った血液型不適合骨髄移植20例において, その有用性について検討した. COBE Spectra を用いた骨髄濃縮により, 赤血球量は98.4%除去され, 最終赤血球量は4.2±2.4mlであった. 有核細胞回収率は34.0±8.38%, CD34陽性細胞回収率は112.3±36.3%であった. 20症例全例で, 移植後の溶血反応および生着不全は認めず, 移植後造血回復は速やかであった. COBE Spectra を用いることで, 清潔な無菌閉鎖回路内において骨髄濃縮が可能となり, 処理時間も短縮された. 種々の細胞免疫療法の用途で広く普及しているCOBE Spectra を用いた骨髄濃縮法は, 血液型不適合骨髄移植における骨髄濃縮の標準的方法として有用であると考えられた.

FTY720によるマウス同種骨髄移植後のドナーリンパ球のアポトーシス誘導とGVHD予防　　　　　　　　　　　　　　　
橋本 大吾, 朝倉 昇司, 松岡 賢市, 佐古田 幸美, 小山 幹子, 青山 一利, 谷本 光音, 赤司 浩一, 豊嶋 崇徳
臨床血液, 47, 9, 1017, 1017, (一社)日本血液学会-東京事務局, 2006年09月
日本語

Transient respiratory disturbance by granulocyte-colony-stimulating factor administration in healthy donors of allogeneic peripheral blood progenitor cell transplantation
Yoshida, I, K Matsuo, T Teshima, D Hashimoto, Y Tanimoto, M Harada, M Tanimoto
TRANSFUSION, 46, 2, 186, 192, 2006年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4(+)CD25(+) T-cell-dependent mechanism
K Matsuoka, T Ichinohe, D Hashimoto, S Asakura, M Tanimoto, T Teshima
BLOOD, 107, 1, 404, 409, 2006年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells
D Hashimoto, S Asakura, S Miyake, T Yamamura, L Van Kaer, C Liu, M Tanimoto, T Teshima
JOURNAL OF IMMUNOLOGY, 174, 1, 551, 556, 2005年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Paclitaxel administered weekly in patients with docetaxel-resistant metastatic breast cancer: A single-center study
M Sawaki, Y Ito, D Hashimoto, N Mizunuma, S Takahashi, N Horikoshi, K Tada, F Kasumi, F Akiyama, G Sakamoto, T Imai, A Nakao, K Hatake
TUMORI, 90, 1, 36, 39, 2004年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Successful treatment with cyclosporin A of myelodysplastic syndrome with erythroid hypoplasia associated with t(6;8)(q15;q22)
S Takata, K Kojima, N Fujii, K Kaneda, C Yoshida, D Hashimoto, S Asakura, K Shinagawa, M Tanimoto
CANCER GENETICS AND CYTOGENETICS, 140, 2, 167, 169, 2003年01月, ［査読有り］
英語, 研究論文（学術雑誌）

クローン病に対しインフリキシマブ治療歴のある肝脾T細胞リンパ腫に対して臍帯血移植を施行した1例
鈴木陶磨, 大東寛幸, 宮下直樹, 須藤啓斗, 日高大輔, 小笠原励起, 杉田純一, 小野澤真弘, 橋本大吾, 豊嶋崇徳, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 44th, 2022年

Outcome of allogeneic hematopoietic stem cell transplantation for follicular lymphoma relapsing after autologous transplantation: analysis of the Japan Society for Hematopoietic Cell Transplantation
Masatoshi Sakurai, Takehiko Mori, Koji Kato, Minoru Kanaya, Shohei Mizuno, Souichi Shiratori, Toshio Wakayama, Naoyuki Uchida, Hikaru Kobayashi, Kohmei Kubo, Itsuto Amano, Takanori Ohta, Yasuhiko Miyazaki, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Eisei Kondo, Yoshiaki Usui, Harumi Kato, Hirofumi Taji, Shohei Mizuno, Kiyohito Hayashi, Yuichiro Nawa, Risa Hashida, Daigo Hashimoto, Hideki Goto, Takahito Kawata, Minoru Kanaya, Kazutaka Ozeki, Kodai Kuriyama, Marie Ohbiki, Kazunori Imada, Shinichi Kako, Kana Sakamoto, Kazuaki Kameda, Kazuki Yoshimura, Hideaki Nitta, Yasunobu Sekiguchi, Hiroyuki Takahashi, Rika Sakai, Shuichi Mizuta, Hiroyuki Takamatsu, Risa Shimizu-Koresawa, Keisuke Kataoka, Nobuhiro Hiramoto, Kimimori Kamijo, Masashi Nishikubo, Fumiya Wada, Junji Suzumiya, Kazunari Aoki, Mizuki Watanabe, Tomoyasu Jo, Yusuke Toda, Yutaka Shimazu, Hiroatsu Ago, Kana Miyazaki, Tomohiko Aoki, Shunsuke Kunou, Koji Izutsu, Tatsuya Suzuki, Sung Won Kim, Satoshi Yamasaki, Hiroatsu Iida, Isao Yoshida, Akihiro Yokoyama, Yoshitaka Asakura, Kazuki Sakatoku, Hiroyasu Ogawa, Kenjiro Mitsuhashi, Takahiro Okada, Tsutomu Takahashi, Ritsuro Suzuki, Ayumi Fujimoto, Fumihiro Ishida, Takashi Ikeda, Kanako Yoshitsugu, Ikue Shiki, Shingo Yano, Yutaro Kamiyama, Dai Chihara, Akihito Nagata, Michiho Ebihara, Shinohara Akihito, Daisuke Kaji, Go Yamamoto, Satoko Morishima, Shinobu Tamura, Bone Marrow Transplantation, 56, 6, 1462, 1466, 2021年06月
速報，短報，研究ノート等（学術雑誌）

難治性DLBCLに対するCAR-T療法施行後に発症した進行性多巣性白質脳症の一例
森木朝子, 大東寛幸, 宮下直樹, 須藤啓斗, 日高大輔, 安本篤史, 後藤秀樹, 杉田純一, 小野澤真弘, 橋本大吾, 豊嶋崇徳, 日本造血細胞移植学会総会プログラム・抄録集, 43rd, 2021年

同種造血幹細胞移植後の体液貯留は予後不良である
宮下直樹, 須藤啓斗, 日高大輔, 大東寛幸, 荒隆英, 白鳥聡一, 安本篤史, 後藤秀樹, 杉田純一, 小野澤真弘, 中川雅夫, 遠藤知之, 橋本大吾, 豊嶋崇徳, 日本造血細胞移植学会総会プログラム・抄録集, 43rd, 2021年

急性GVHD・クローン病に対する羊膜由来間葉系幹細胞の医師主導治験 兵庫医科大学発・初認定ベンチャーによる開発をめざして
山原 研一, 濱田 彰子, 大西 俊介, 相馬 俊裕, 岡本 里香, 中村 志郎, 岡田 昌也, 吉原 哲, 吉原 享子, 橋本 大吾, 磯江 敏幸, 豊嶋 崇徳, 佐藤 典宏, 藤盛 好啓, 兵庫医科大学医学会雑誌, 43, 1, 41, 45, 2018年09月
兵庫医科大学医学会, 日本語

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
(一社)日本血液学会-東京事務局, 日本語

羊膜由来間葉系幹細胞による急性GVHD治療 (特集 間葉系幹細胞移植のupdate)
山原 研一, 濵田 彰子, 大西 俊介, 黒田 将子, 相馬 俊裕, 岡本 里香, 岡田 昌也, 吉原 哲, 吉原 享子, 橋本 大吾, 磯江 敏幸, 豊嶋 崇徳, 佐藤 典宏, 小川 啓恭, 藤盛 好啓, 臨床免疫・アレルギー科 = Clinical immunology & allergology, 70, 1, 18, 24, 2018年07月
科学評論社, 日本語

羊膜間葉系幹細胞の細胞製剤化と急性GVHDに対する第I/II相医師主導治験
山原研一, 浜田彰子, 黒田将子, 岡田昌也, 岡田昌也, 吉原享子, 吉原哲, 相馬俊裕, 橋本大吾, 佐藤典宏, 豊嶋崇徳, 小川啓恭, 藤盛好啓, 日本輸血細胞治療学会誌, 64, 2, 451, 451, 2018年04月23日
(一社)日本輸血・細胞治療学会, 日本語

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
(一社)日本輸血・細胞治療学会, 日本語

末梢血幹細胞採取におけるSpectra Optia^Ⓡ MNCモードとCMNCモードの後方視的検討
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, 2018年
<p><b>背景：</b>Spectra Optia^Ⓡ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^Ⓡ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>, 一般社団法人 日本輸血・細胞治療学会, 日本語

末梢血幹細胞採取におけるCD34陽性細胞採取効率不良であった血小板数高値の症例
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
日本語

HEMATOLOGICAL MALIGNANCIES IN SOLID ORGAN TRANSPLANT RECIPIENTS: RETROSPECTIVE SINGLE-CENTER ANALYSIS IN JAPAN
K. Fujimoto, I. Daiki, R. Goto, K. Morita, T. Ooka, K. Hatanaka, H. Goto, J. Sugita, M. Onozawa, D. Hashimoto, K. Kahata, T. Kondo, Y. Matsuno, T. Shimamura, T. Teshima, HAEMATOLOGICA, 102, 693, 693, 2017年06月
英語, 研究発表ペーパー・要旨（国際会議）

IMATINIB VS. DASATINIB FOR OUTCOMES AFTER ALLOGENEIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH PH plus ACUTE LYMPHOBLASTIC LEUKEMIA
A. Shigematsu, S. Ota, H. Goto, K. Minauchi, J. Sugita, D. Hashimoto, M. Obara, T. Endo, M. Imamura, T. Teshima, N. Kobayashi, HAEMATOLOGICA, 102, 354, 354, 2017年06月
英語, 研究発表ペーパー・要旨（国際会議）

当院においてドナーリンパ球輸注を施行した34症例の検討　　　　　　　　　　　　　　　
石尾 崇, 立野 貴大, 笠原 耕平, 小杉 瑞葉, 白鳥 聡一, 岡田 耕平, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 遠藤 知之, 近藤 健, 豊嶋 崇徳, 日本輸血細胞治療学会誌, 63, 2, 148, 149, 2017年04月
(一社)日本輸血・細胞治療学会, 日本語

Vitamin A-Coupled Liposomes Carrying siRNA Against HSP47 Ameliorate Skin Fibrosis in Chronic Graft-Versus-Host Disease
Tomohiro Yamakawa, Daigo Hashimoto, Eiko Hayase, Shuichiro Takahashi, Takanori Teshima, BLOOD, 128, 22, 2016年12月
英語, 研究発表ペーパー・要旨（国際会議）

胆嚢炎症状を契機に発症したTAFRO症候群　　　　　　　　　　　　　　　
関根 隆博, 後藤 秀樹, 日高 大輔, 早瀬 英子, 小杉 瑞葉, 岡田 耕平, 白鳥 総一郎, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 遠藤 知之, 近藤 健, 豊嶋 崇徳, 臨床血液, 57, 12, 2608, 2608, 2016年12月
(一社)日本血液学会-東京事務局, 日本語

HIV感染症合併血友病患者に対するMRIによる脳スクリーニングの意義
遠藤知之, 遠藤知之, 宮下直洋, 宮下直洋, 笠原耕平, 笠原耕平, 小杉瑞葉, 岡田耕平, 白鳥聡一, 後藤秀樹, 杉田純一, 小野澤真弘, 橋本大吾, 加畑馨, 藤本勝也, 藤本勝也, 近藤健, 橋野聡, 橋野聡, 豊嶋崇徳, 豊嶋崇徳, 日本エイズ学会誌, 18, 4, 439, 439, 2016年11月20日
(一社)日本エイズ学会, 日本語

肺胞蛋白症を合併し致死的な経過を辿った骨髄異形成症候群の1例　　　　　　　　　　　　　　　
大東 寛幸, 松川 敏大, 金谷 穣, 後藤 秀樹, 橋本 大吾, 加畑 馨, 遠藤 知之, 田中 伸哉, 豊嶋 崇徳, 臨床血液, 57, 11, 2398, 2398, 2016年11月
(一社)日本血液学会-東京事務局, 日本語

HIV感染症合併血友病患者に対するMRIによる脳スクリーニングの意義　　　　　　　　　　　　　　　
遠藤 知之, 宮下 直洋, 笠原 耕平, 小杉 瑞葉, 岡田 耕平, 白鳥 聡一, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 近藤 健, 橋野 聡, 豊嶋 崇徳, 日本エイズ学会誌, 18, 4, 439, 439, 2016年11月
日本エイズ学会, 日本語

当院における同種末梢血幹細胞採取の検討
杉田 純一, 大東 寛幸, 橋口 淳一, 松川 敏大, 金谷 穣, 小杉 瑞葉, 松岡 里湖, 後藤 秀樹, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 遠藤 知之, 近藤 健, 豊嶋 崇徳, 日本輸血細胞治療学会誌, 62, 3, 490, 490, 2016年06月
(一社)日本輸血・細胞治療学会, 日本語

Spectra Optiaによる末梢血幹細胞採取の検討
伊藤 誠, 加畑 馨, 渡邊 千秋, 上床 貴代, 米岡 麻記, 茂木 祐子, 成田 玲子, 魚住 諒, 石岡 聡子, 早坂 光司, 渋谷 斉, 小杉 瑞葉, 重松 明男, 高橋 正二郎, 杉田 純一, 橋本 大吾, 佐藤 典宏, 豊嶋 崇徳, 清水 力, 日本輸血細胞治療学会誌, 62, 3, 490, 490, 2016年06月
(一社)日本輸血・細胞治療学会, 日本語

当院における骨髄腫患者からの末梢血幹細胞動員効率の検討
加畑馨, 加畑馨, 伊藤誠, 渡邊千秋, 上床貴代, 米岡麻記, 小杉瑞葉, 小杉瑞葉, 重松明男, 重松明男, 高橋正二郎, 高橋正二郎, 杉田純一, 橋本大吾, 山本聡, 佐藤典宏, 清水力, 豊嶋崇徳, 日本輸血細胞治療学会誌, 62, 2, 402, 402, 2016年04月01日
(一社)日本輸血・細胞治療学会, 日本語

当院におけるSpectraとOptia 2モードの使用経験　　　　　　　　　　　　　　　
伊藤 誠, 加畑 馨, 渡邊 千秋, 上床 貴代, 米岡 麻記, 小杉 瑞葉, 重松 明男, 高橋 正二郎, 杉田 純一, 橋本 大吾, 佐藤 典宏, 豊嶋 崇徳, 清水 力, 日本輸血細胞治療学会誌, 62, 2, 299, 299, 2016年04月
(一社)日本輸血・細胞治療学会, 日本語

移植片対宿主病(GVHD)の分子病態と分子標的療法 (特集 同種造血幹細胞移植に関する最近の展開)
高橋 秀一郎, 橋本 大吾, 豊嶋 宗徳, 血液内科 = Hematology, 72, 3, 330, 336, 2016年03月
科学評論社, 日本語

Topical Ruxolitinib Protects LGR5+Stem Cells in the Hair Follicle and Ameliorates Skin Graft-Versus-Host Disease
Shuichiro Takahashi, Daigo Hashimoto, Eiko Hayase, Takanori Teshima, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 22, 3, S21, S22, 2016年03月
英語, 研究発表ペーパー・要旨（国際会議）

真菌感染によるGVHD発症のメカニズム
橋本 大吾, 瓜生 英尚, 豊嶋 崇徳, 血液内科 = Hematology, 71, 6, 775, 780, 2015年12月
科学評論社, 日本語

R-spondin1 Promotes Paneth Cell Growth, Maintains Intestinal Microbial Ecology, and Ameliorates GvHD
Eiko Hayase, Daigo Hashimoto, Kiminori Nakamura, Yoshitoshi Ogura, Tetsuya Hayashi, Ken Kurokawa, Tokiyoshi Ayabe, Takanori Teshima, BLOOD, 126, 23, 2015年12月
英語, 研究発表ペーパー・要旨（国際会議）

初回ART導入におけるRaltegravirとDolutegravirの血液毒性への関与
後藤秀樹, 後藤秀樹, 遠藤知之, 藤本勝也, 近藤健, 加畑馨, 橋本大吾, 小野澤真弘, 杉田純一, 松川敏大, 笠原耕平, 宮下直洋, 橋野聡, 佐藤典宏, 豊嶋崇徳, 日本エイズ学会誌, 17, 4, 510, 510, 2015年11月20日
(一社)日本エイズ学会, 日本語

Cardio-ankle vascular index(CAVI)を用いたHIV感染者の動脈硬化の評価とリスク因子の検討　　　　　　　　　　　　　　　
遠藤 知之, 宮下 直洋, 笠原 耕平, 渡部 恵子, 武内 阿味, 松川 敏大, 金谷 穣, 小杉 瑞葉, 松岡 里湖, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 近藤 健, 橋野 聡, 豊嶋 崇徳, 日本エイズ学会誌, 17, 4, 392, 392, 2015年11月
日本エイズ学会, 日本語

IDENTIFICATION OF FIP1L1-PDGFRA ASSOCIATING MOLECULE THAT LOCATES IN THE NUCLEUS AND AUGMENTS THE ACTIVITY OF FIP1L1-PDGFRA
T. Kondo, M. Ibata, J. Iwasaki, Y. Fujioka, K. Nakagawa, S. Darmanin, M. Onozawa, D. Hashimoto, Y. Ohba, S. Hatakeyama, T. Teshima, HAEMATOLOGICA, 100, 327, 327, 2015年06月
英語, 研究発表ペーパー・要旨（国際会議）

Graft-Versus-Host Disease Targets Granulosa Cell of Ovarian Follicle and Causes Infertility after Allogeneic Hematopoietic Stem Cell Transplantation
Sonoko Shimoji, Daigo Hashimoto, Koji Kato, Hidetsugu Tujigiwa, Koichi Akashi, Takanori Teshima, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 21, 2, S26, S27, 2015年02月
英語, 研究発表ペーパー・要旨（国際会議）

顆粒球採取におけるSpectra Optiaの採取効率ならびにドナーへの影響
岡田耕平, 杉田純一, 伊藤誠, 米岡麻記, 櫻澤貴代, 渡邊千秋, 橋本大吾, 重松明男, 佐藤典宏, 清水力, 豊嶋崇徳, 日本輸血細胞治療学会誌, 60, 2, 409, 409, 2014年04月10日
(一社)日本輸血・細胞治療学会, 日本語

免疫学からみた造血幹細胞移植 (特集 造血幹細胞移植)
橋本 大吾, 細胞, 45, 11, 512, 515, 2013年10月
ニューサイエンス社, 日本語

Therapeutic efficacy of antitumor monoclonal antibodies combined with chemotherapy depends on innate immunity and NK1.1-innate lymphoid cells.
Marina Moskalenko, Michael Pan, Daigo Hashimoto, Arthur Mortha, Sebastian G. Bernardo, Marylene Leboeuf, Alan Houghton, Jedd Wolchok, Steven Burakoff, Miriam Merad, Yvonne M. Saenger, CANCER RESEARCH, 73, 2013年01月
英語, 研究発表ペーパー・要旨（国際会議）

CD169(+) Macrophages Regulate Erythropoiesis Under Homeostasis, Recovery From Erythron Injury and in JAK2(V617F)-Induced Polycythemia Vera
Andrew Chow, Matthew Huggins, Jalal Ahmed, Daniel Lucas, Daigo Hashimoto, Yuya Kunisaki, Sandra Pinho, Marylene Leboeuef, Clara Noizat, Nico van Rooijen, Masato Tanaka, Zlizhuang Joe Zhao, Aviv Bergman, Miriam Merad, Paul S. Frenette, BLOOD, 120, 21, 2012年11月
英語, 研究発表ペーパー・要旨（国際会議）

Dendritic Cell Derived C3a/C5a Mediate Murine Graft Versus Host Disease.
W. -H Kwan, D. Hashimoto, E. Paz-Artal, K. Ostrow, M. Greter, M. Merad, P. S. Heeger, AMERICAN JOURNAL OF TRANSPLANTATION, 11, 152, 152, 2011年04月
英語, 研究発表ペーパー・要旨（国際会議）

Anti-tyrosinase related protein 1 (TRP1) antibody combined with cyclophosphamide induces adaptive immunity against melanoma
Yvonne M. Saenger, Michael Pan, Daigo Hashimoto, Bradley Glodny, Shaily Shah, Alan N. Houghton, Taha Merghoub, Jedd D. Wolchok, Miriam Merad, CANCER RESEARCH, 71, 2011年04月
英語, 研究発表ペーパー・要旨（国際会議）

Pre-Transplant CSF-1 Therapy Expands the Recipient Macrophage Pool and Modulates Graft Versus Host Disease After Allogeneic Hematopoietic Cell Transplantation
Daigo Hashimoto, Andrew Chow, Melanie Greter, Marylene Leboeuf, Florent Ginhoux, Takanori Teshima, Miriam Merad, BLOOD, 116, 21, 112, 112, 2010年11月
英語, 研究発表ペーパー・要旨（国際会議）

Protection of the Intestinal Epithelium from Conditioning with R-spondin1 Ameliorates Graft-Versus-Host Disease
Shuichiro Takashima, Kazutoshi Aoyama, Motoko Koyama, Daigo Hashimoto, Takeshi Oshima, Kazuma Tomizuka, Koichi Akashi, Takanori Teshima, BLOOD, 112, 11, 32, 32, 2008年11月
英語, 研究発表ペーパー・要旨（国際会議）

Host plasmacytoid or conventional dendritic cells alone are sufficient to initiate graft-versus-host disease
Motoko Koyama, Daigo Hashimoto, Kazutoshi Aoyama, Ken-ichi Matuoka, Kennosuke Karube, Kiyoshi Takeda, Koichi Ohshima, Koichi Akashi, Mitsune Tanimoto, Mine Harada, Takanori Teshima, BLOOD, 110, 11, 643A, 644A, 2007年11月
英語, 研究発表ペーパー・要旨（国際会議）

Alloantigens expression on host non-hematopoietic cells leads to donor T cell exhaustion and reduces GVL effects
D. Hashimoto, S. Asakura, K. -I. Matsuoka, Y. Sakoda, M. Koyama, K. Aoyama, M. Tanimoto, T. Teshima, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 13, 2, 108, 108, 2007年02月
英語, 研究発表ペーパー・要旨（国際会議）

Donor-reactive thymic-dependent Th1 cells cause chronic GVHD
Y. Sakoda, D. Hashimoto, S. Asakura, K. Takeuchi, M. Harada, M. Tanimoto, T. Teshima, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 13, 2, 16, 16, 2007年02月
英語, 研究発表ペーパー・要旨（国際会議）

Early recovery of host T cells predicts primary graft rejection following non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation
M. Koyama, D. Hashimoto, K. Kamezaki, A. Numata, Y. Sakoda, K. Aoyama, K. Takenaka, T. Miyamoto, N. Harada, K. Nagafuji, K. Akashi, M. Tanimoto, M. Harada, T. Teshima, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 13, 2, 127, 127, 2007年02月
英語, 研究発表ペーパー・要旨（国際会議）

Homeostatic proliferation of donor T cells reduces their capacity for inducing acute graft-versus-host disease.
Y Maeda, T Teshima, D Hashimoto, M Tammoto, P Reddy, BLOOD, 106, 11, 378A, 378A, 2005年11月
英語, 研究発表ペーパー・要旨（国際会議）

Impaired thymic negative selection causes chronic graft-versus-host disease after allogeneic bone marrow transplantation.
Y Sakoda, D Hashimoto, K Takeuchi, S Asakura, K Akashi, M Tanimoto, M Harada, T Teshima, BLOOD, 106, 11, 137A, 137A, 2005年11月
英語, 研究発表ペーパー・要旨（国際会議）

Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+CD25+T cell-dependent mechanism.
KI Matsuoka, T Ichinohe, S Asakura, D Hashimoto, M Tanimoto, T Teshima, BLOOD, 106, 11, 136A, 136A, 2005年11月
英語, 研究発表ペーパー・要旨（国際会議）

FTY720-induced sequestration of donor T cells in lymph nodes leads to activation-induced apoptosis of alloreactive T cells and reduced graft-versus-host disease.
D Hashimoto, S Asakura, K Matsuoka, Y Sakoda, M Tanimoto, T Teshima, BLOOD, 104, 11, 836A, 836A, 2004年11月
英語, 研究発表ペーパー・要旨（国際会議）

Alloantigen expression on host target epithelium inhibits graft-versus-leukemia (GVL) effects.
S Asakura, D Hashimoto, K Matsuoka, Y Sakoda, M Tanimoto, T Teshima, BLOOD, 104, 11, 172A, 172A, 2004年11月
英語, 研究発表ペーパー・要旨（国際会議）

Host NKT cells promote Th2 polarization of donor T cells and regulate acute GVHD after experimental BMT via a STAT6-dependent mechanism.
D Hashimoto, S Asakura, S Miyake, T Yamamura, L Van Kaer, M Tanimoto, T Teshima, BLOOD, 102, 11, 191A, 192A, 2003年11月
英語, 研究発表ペーパー・要旨（国際会議）

Fournier's gangrene after unrelated cord blood stem cell transplantation.
C Yoshida, K Kojima, K Shinagawa, D Hashimoto, S Asakura, S Takata, M Tanimoto, Annals of hematology, 81, 9, 538, 9, 2002年09月, ［査読有り］, ［国際誌］
英語

Dose-finding phase I study of simultaneous weekly infusion with doxorubicin and docetaxel in patients with advanced breast cancer.
Y Ito, K Aiba, N Horikoshi, T Saotome, T Irie, K Sugiyama, M Nakane, D Hashimoto, N Yoshida, N Mizunuma, S Takahashi, Y Tanigawara, International journal of clinical oncology, 6, 5, 242, 7, 2001年10月, ［査読有り］, ［国内誌］
Springer Japan, 英語

専門医のための血液病学　　　　　　　　　　　　　　　
橋本 大吾, 4. 免疫担当細胞とその分化機構 1)自然免疫, 5. 造血幹細胞移植 4)GVHD
医学書院, 2021年12月, ［分担執筆］

造血細胞移植看護基礎テキスト
日本造血・免疫細胞療法学会, 第1章造血幹細胞移植の基礎知識 4. 移植免疫
南江堂, 2021年06月, 9784524228270, vii, 234p, 日本語, ［分担執筆］

EBM血液疾患の治療〈2019‐2020〉
押味, 和夫, 金倉, 譲, 木崎, 昌弘, 鈴木, 律朗, 神田, 善伸, 腸内細菌が同種移植後の経過に及ぼす影響 P525-531
中外医学社, 2019年11月, 4498125126, 冊, 日本語, ［分担執筆］

みんなに役立つGVHD(移植片対宿主病)の基礎と臨床
豊嶋, 崇徳, 自然免疫とGVHD p86-90
医薬ジャーナル社, 2013年08月, 9784753226320, 423p, 日本語, ［分担執筆］