Research activity information

• Philadelphia chromosome-negative but BCR::ABL1-positive acute lymphoblastic leukemia: a real-world multicenter cohort study.
  Shota Yokoyama; Masahiro Onozawa; Hiroyuki Kimura; Takahide Ara; Jun Nagai; Shota Yoshida; Naoki Miyashita; Toshihiro Matsukawa; Hideki Goto; Shinsuke Hirabayashi; Minoru Kanaya; Akio Mori; Daisuke Hidaka; Junichi Hashiguchi; Kentaro Wakasa; Makoto Ibata; Yukari Takeda; Takuto Miyagishima; Satoshi Yamamoto; Katsuya Fujimoto; Toma Suzuki; Tomoyuki Saga; Hajime Sakai; Yasutaka Kakinoki; Tatsuo Oyake; Takeshi Kondo; Takanori Teshima
  International journal of hematology, 22 Apr. 2026, [Domestic magazines]
  English, Scientific journal, Chronic myelogenous leukemia that carries the BCR::ABL1 fusion gene without cytogenetically detectable Philadelphia (Ph) chromosomes is termed masked Ph. However, the prevalence and clinical relevance of masked Ph in acute lymphoblastic leukemia (ALL) remain unclear. Using the Hokkaido Leukemia Net real-world multicenter cohort, we analyzed 160 B-cell ALL patients diagnosed between 2017 and 2024 with available cytogenetic and molecular data. Among 92 BCR::ABL1-positive cases, 19 (20.7%) lacked a cytogenetically visible Ph chromosome and were classified as masked-Ph ALL. Compared with Ph + ALL, masked-Ph patients were older and had lower white blood cell counts and bone marrow blast percentages at diagnosis. Most BCR::ABL1-positive patients received tyrosine kinase inhibitors (TKIs) during induction, resulting in comparable complete remission rates and similar overall survival between masked-Ph and Ph + ALL; both groups showed superior outcomes compared with BCR::ABL1-negative ALL. The number of metaphases analyzed by G-banding was significantly lower in masked-Ph ALL, suggesting underdetection by conventional cytogenetics. One case exhibited an atypical FISH pattern consistent with a cryptic microinsertion. These findings indicate that masked-Ph ALL is relatively common and may be overlooked without molecular testing, underscoring the importance of incorporating RT-PCR and FISH at diagnosis.
• A Case of Acute Myeloid Leukemia with MOZ::TIF2 Fusion Gene Resulting from a Novel Breakpoint.
  Toma Suzuki; Masahiro Onozawa; Minoru Kanaya; Takeshi Kondo; Shunsuke Sugimura; Jun Nagai; Keito Yokoyama; Yumika Saito; Shota Yoshida; Shinpei Harada; Keito Suto; Yuta Hasegawa; Takahide Ara; Hideki Goto; Daigo Hashimoto; Takanori Teshima
  Internal medicine (Tokyo, Japan), 21 Apr. 2026, [Domestic magazines]
  English, Scientific journal, We report a rare case of acute myeloid leukemia (AML) harboring an MOZ::TIF2 fusion gene with a previously unreported breakpoint. A 36-year-old man was diagnosed with AML involving inv(8)(p11.2q13). Reverse transcriptase-polymerase chain reaction (RT-PCR) initially failed to detect the conventional MOZ exon16::TIF2 exon14 fusion associated with inv(8)(p11.2q13); however, further sequencing identified a novel breakpoint of MOZ exon14::TIF2 exon12, with an additional shorter transcript lacking TIF2 exon13. MOZ::TIF2-positive AML is extremely rare, with only eight cases previously reported, and adult cases appear to have particularly poor outcomes. Our case highlights the diagnostic challenges and aggressive clinical behavior associated with MOZ::TIF2-rearranged AML.
• Successful treatment with zanubrutinib for Bing-Neel syndrome progressing on ibrutinib: a case report and literature review.
  Shingo Nojima; Toru Miyajima; Reiki Ogasawara; Shota Yoshida; Hiroyuki Kimura; Rintaro Nozu; Fuka Horikita; Takahide Ara; Toshihiro Matsukawa; Souichi Shiratori; Masahiro Onozawa; Masao Nakagawa; Takanori Teshima
  Leukemia & lymphoma, 1, 4, 08 Apr. 2026, [International Magazine]
  English, Scientific journal
• Real-world outcomes of tisagenlecleucel treatment in patients with relapsed or refractory large B-cell lymphomas: a nationwide registry.
  Masatoshi Sakurai; Yasuyuki Arai; Hideki Goto; Haryoon Kim; Kyoko Masuda; Toshio Kitawaki; Nobuharu Fujii; Tatsu Shimoyama; Satoshi Yoshihara; Jun Kato; Takahide Ara; Seitaro Terakura; Yoshihiro Umezawa; Hideyuki Nakazawa; Miki Ando; Yuji Shimura; Nobuhiro Kanemura; Koichi Onodera; Yasuhiro Nakashima; Hirokazu Tanaka; Yoshiko Atsuta; Keisuke Kataoka; Koji Kato
  Cytotherapy, 28, 3, 102042, 102042, Mar. 2026, [International Magazine]
  English, Scientific journal, BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has transformed treatment for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, real-world data in Japan remain limited. METHODS: We retrospectively analyzed 489 LBCL patients treated with tisagenlecleucel (tisa-cel) using a nationwide registry. RESULTS: The median patient age was 62 years, with 89% having undergone ≥3 prior therapies. At infusion, 22% were in a complete response. The estimated 1-year progression-free survival (PFS) and overall survival (OS) rates were 43.2% (95%CI, 37.8-49.3%) and 65.9% (95% CI, 61.0-71.1%), respectively. Multivariable analysis revealed that better Karnofsky performance status, a history of stem cell transplantation, absence of extranodal lesion, higher absolute lymphocyte count, and lower lactate dehydrogenase level prior to lymphodepleting therapy were significantly associated with better PFS and OS. Older age (≥65 years) at infusion was associated with better PFS, while shorter duration from apheresis to infusion (<60 days) was associated with better OS. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 71% and 5% of patients, respectively. CONCLUSIONS: This study provides the largest real-world dataset on tisa-cel treatment for LBCL. Our results showed real-world outcomes and early safety consistent with prior trials.
• Disease status at CAR T-cell infusion in relapsed or refractory large B-cell lymphoma: prognostic significance for real-world outcomes, irrespective of bridging therapy.
  Yu Yagi; Yusuke Kanemasa; Hideki Goto; Masahide Yamamoto; Kotaro Miyao; Maki Hagihara; Toshio Kitawaki; Tatsu Shimoyama; Ryo Hanajiri; Shinichi Makita; Go Yamamoto; Masatoshi Sakurai; Nobuharu Fujii; Takahide Ara; Yasuhiro Nakashima; Akiyo Yoshida; Hideyuki Nakazawa; Emiko Sakaida; Nobuhiro Kanemura; Haryoon Kim; Keisuke Kataoka; Yoshiko Atsuta; Koji Kato
  Bone marrow transplantation, 14 Feb. 2026, [International Magazine]
  English
• Safety and Efficacy of Graft-versus-Host Disease Prophylaxis with Mini-Dose Methotrexate in Umbilical Cord Blood Transplantation: An NJHSG-CBT18 Observational Study.
  Souichi Shiratori; Keito Suto; Yuta Hasegawa; Takahide Ara; Toshihiro Matsukawa; Hideki Goto; Masahiro Onozawa; Masao Nakagawa; Kaoru Kahata; Daisuke Hidaka; Reiki Ogasawara; Kohei Okada; Junichi Sugita; Yasutaka Kakinoki; Shuichi Ota; Daigo Hashimoto; Takanori Teshima
  Transplantation and cellular therapy, 06 Nov. 2025, [International Magazine]
  English, Scientific journal, Tacrolimus (Tac) and methotrexate (MTX) are standard graft-versus-host disease (GVHD) prophylaxis for umbilical cord blood transplantation (CBT); however, the optimal dose of MTX for CBT remains to be determined. We previously showed the safety and efficacy of reduced-dose MTX (mini-MTX; 5 mg/m2 on days 1, 3, and 6) combined with Tac as GVHD prophylaxis for CBT in a single-center retrospective study. Here we report a multicenter observational study in the North Japan Hematology Study Group (NJHSG; NJHSG-CBT18) conducted to evaluate transplantation outcomes according to GVHD prophylaxis in single-unit CBT, in which patients with hematologic malignancies scheduled for CBT were prospectively registered and followed for 2 years after CBT. A total of 112 patients were registered in NJHSG-CBT18, with a median age of 51 years. Eighty-nine patients received Tac + mini-MTX, 19 patients received Tac + mycophenolate mofetil (MMF), and 4 patients received Tac only as GVHD prophylaxis. Multivariate analysis identified GVHD prophylaxis other than Tac + mini-MTX as a significant risk factor for nonrelapse mortality (NRM) (hazard ratio [HR], 0.160; 95% confidence interval [CI], 0.065 to 0.391; P < .001), overall survival (OS) (HR, 2.971; 95% CI, 1.558 to 5.663; P < .001), progression-free survival (PFS) (HR, 2.383; 95% CI, 1.345 to 4.222; P = .003), and GVHD-free, relapse-free survival (GRFS) (HR, 3.075; 95% CI, 1.799 to 5.256; P < .001). In a comparison of clinical outcomes between the mini-MTX and MMF groups, the cumulative incidences of pre-engraftment immune reaction (5.7% versus 42.1%; P < .001), human herpesvirus 6 encephalitis (2.3% versus 15.8%, P = .011), grade II-IV acute GVHD (14.6% versus 47.4%, P < .001), and NRM (1.1% versus 52.6%, P < .001) were significantly lower and the cumulative incidence of immunosuppressant discontinuation was significantly higher (66.3% versus 18.4%, P = .004) in the mini-MTX group compared to the MMF group, while rates of chronic GVHD and relapse were comparable between the groups. The probabilities of OS (70.6% versus 31.6%, P < .001), PFS (58.1 versus 14.0%, P < .001), and GRFS (44.9% versus 5.1%, P < .001) were significantly higher in the mini-MTX group. Multivariate analysis of risk factors for OS in the mini-MTX group identified high-risk or very high-risk refined Disease Risk Index (rDRI) (HR, 3.896; 95% CI, 1.575 to 9.637; P = .003) and high HCT-CI (HR, 3.338; 95% CI, 1.301 to 8.569; P = .012) as significant risk factors for OS. Our data indicate that a combination of Tac + mini-MTX is safe and effective GVHD prophylaxis in CBT.
• Heterogeneity of Survival Benefit Conferred By Letermovir
  Yu Akahoshi; Hideki Nakasone; Katsuto Takenaka; Takahide Ara; Yuma Tada; Noriko Doki; Naoyuki Uchida; Masatsugu Tanaka; Yuta Hasegawa; Wataru Takeda; Tetsuya Nishida; Jun Ishikawa; Naoki Kurita; Masashi Sawa; Makoto Onizuka; Shinichi Kako; Shin-Ichiro Fujiwara; Keisuke Kataoka; Koji Kawamura; Takahiro Fukuda; Yoshiko Atsuta; Kimikazu Yakushijin; Yoshinobu Kanda
  Transplantation and Cellular Therapy, 31, 7, 461.e1, 461.e12, Elsevier BV, Jul. 2025
  Scientific journal
• 同種造血幹細胞移植後のカルシニューリン阻害剤投与時期がドナーT細胞疲弊および慢性GVHD発症に及ぼす影響の検討
  千丈 創; 橋本 大吾; 塚本 しほり; 久保田 晋平; 伊藤 歩; 田中 喬; 一木 朝絵; 岡田 怜; 齋藤 祐美花; 宮島 徹; 李 文玉; 張 紫旋; 原田 晋平; 長谷川 祐太; 荒 隆英; 長谷川 嘉則; 稲本 賢弘; 村上 正晃; 福田 隆浩; 豊嶋 崇徳
  日本輸血細胞治療学会誌, 71, 2, 333, 333, (一社)日本輸血・細胞治療学会, Apr. 2025
  Japanese
• Impact of HLA Epitope Matching on Outcomes in Haploidentical HSCT With Distinct GVHD Prophylaxes
  Makoto Iwasaki; Junya Kanda; Hidenori Tanaka; Kazuhiro Ikegame; Takero Shindo; Takakazu Kawase; Satoshi Yoshihara; Noriko Doki; Hirohisa Nakamae; Tetsuya Eto; Takashi Tanaka; Takahide Ara; Nobuhiro Hiramoto; Yukio Kondo; Ken-Ichi Matsuoka; Toshihiko Ando; Katsuhiro Shono; Koji Nagafuji; Takahiro Fukuda; Tatsuo Ichinohe; Yoshiko Atsuta; Makoto Murata; Satoko Morishima
  Transplantation, 109, 7, 1241, 1250, Ovid Technologies (Wolters Kluwer Health), 14 Feb. 2025
  Scientific journal, Background.
  
  The introduction of posttransplant cyclophosphamide (PTCy) for prophylaxis against graft-versus-host disease (GVHD) has led to an increase in the number of transplants from haploidentical donors. Accordingly, we aimed to understand the impact of HLA epitope mismatch on the outcomes of haploidentical hematopoietic stem cell transplantation (HSCT) with prophylaxis against GVHD.
  
  Methods.
  
  This retrospective study included 1037 patients who underwent their first HSCT for hematologic malignancies from haploidentical peripheral blood donors in a Japanese registry between 2011 and 2019. In total, 542 patients received PTCy and 495 received antithymocyte globulin-based GVHD prophylaxis.
  
  Results.
  
  In patients with high-risk disease who received PTCy, higher class I Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-I) scores were associated with a significantly lower risk of relapse, leading to a higher overall survival (OS: high PIRCHE-I patients compared with low PIRCHE-I patients: relapse: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46-0.98; P = 0.040; mortality: HR, 0.69; 95% CI, 0.46-0.99; P = 0.042). In patients with standard-risk disease who received antithymocyte globulin, a significant association between class II PIRCHE (PIRCHE-II) and a lower incidence of nonrelapse mortality (NRM) leading to higher OS was observed (high PIRCHE-II patients compared with low PIRCHE-II patients, NRM: HR, 0.41; 95% CI, 0.19-0.86; P = 0.019; OS: HR, 0.55; 95% CI, 0.32-0.94; P = 0.030).
  
  Conclusions.
  
  These findings suggest the differential effects of T-cell epitope matching based on GVHD prophylaxis after haploidentical HSCT. Pretransplant disease status may also be important for understanding the graft-versus-leukemia effect of mismatched HLA in haploidentical HSCT using PTCy.
• Severe and/or prolonged COVID-19 in hematologic diseases: clinical implications before and during the omicron era.
  Akinao Okamoto; Masahiro Yoshida; Senji Kasahara; Takahide Ara; Kazutaka Ozeki; Takanobu Morishita; Daisuke Ikeda; Minoru Kanaya; Tomohiro Kajiguchi; Yasuhiro Suzuki; Shingo Kurahashi; Tomohiro Horio; Yoshiaki Marumo; Tatsuo Oyake; Shigeki Saito; Hitomi Sawa; Shun-Ichi Kimura; Takahiro Nishiyama; Eisei Kondo; Junji Hiraga; Hiroki Hosoi; Yasufumi Masaki; Yoshiko Atsuta; Hideyuki Yamamoto; Takahiko Miyama; Naoe Goto; Chisako Iriyama; Keichiro Mihara; Yoshihiro Inamoto; Akihiro Tomita
  Frontiers in oncology, 15, 1687204, 1687204, 2025, [International Magazine]
  English, Scientific journal, BACKGROUND: Although the Omicron variant has been reported to reduce COVID-19 severity in the general population, its impact on patients with hematologic malignancies remains uncertain, and epidemiological investigation is warranted. METHODS: We conducted a multicenter retrospective cohort study of 1, 023 patients with hematologic diseases diagnosed with COVID-19 at 22 centers in Japan between January 2020 and January 2023. Outcomes within 60 days after diagnosis including severe and/or prolonged disease, COVID-19-related mortality, and overall survival (OS) were compared between the pre-Omicron and Omicron periods. Multivariable analysis was performed to identify independent adverse prognostic factors. RESULTS: Severe and/or prolonged disease occurred in 27.5% of patients, COVID-19-related mortality was 6.3%, and OS was 91.4%. Compared with the pre-Omicron period, the Omicron period was associated with significantly lower rates of severe/prolonged disease (26.0% vs. 48.0%, P<0.01) and COVID-19-related mortality (5.0% vs. 15.0%, P<0.01), but no significant difference in OS (92.0% vs. 84.0%, P = 0.62). Age ≥60 years was the strongest predictor of severe/prolonged disease (sHR 3.08, P<0.01) and mortality (HR 8.94, P<0.01). Male sex (sHR 1.38; HR 1.82, both P<0.01) and prior bendamustine exposure (sHR 1.83; HR 1.87, both P<0.01) were also associated with both outcomes, whereas anti-CD38 antibody therapy was linked only to mortality (HR 3.65, P<0.01). CONCLUSION: In patients with hematologic diseases, the Omicron period was associated with reduced severity and COVID-19-related mortality but no improvement in OS. Older age and prior bendamustine exposure were strongly associated with adverse outcomes, highlighting the need for strict infection prevention and prompt, aggressive COVID-19 management in these high-risk populations.
• HIV感染合併血友病患者の運動機能評価およびリハビリテーションの有用性
  遠藤 知之; 渡部 恵子; 原田 裕子; 由利 真; 千田 尊子; 後藤 秀樹; 松川 敏大; 荒 隆英; 長谷川 祐太; 宮島 徹; 長井 惇; 森木 朝子; 藤谷 順子; 豊嶋 崇徳
  日本エイズ学会誌, 26, 4, 380, 380, (一社)日本エイズ学会, Nov. 2024
  Japanese
• AIDS患者の髄液病原体網羅的解析を目的としたマルチプレックスPCRの有用性についての検討
  松川 敏大; 遠藤 知之; 森木 朝子; 長井 惇; 宮島 徹; 長谷川 祐太; 荒 隆英; 後藤 秀樹; 豊嶋 崇徳
  日本エイズ学会誌, 26, 4, 457, 457, (一社)日本エイズ学会, Nov. 2024
  Japanese
• ART療法が奏効した難治性サイトメガロウイルス腸炎の1例
  長谷川 祐太; 遠藤 知之; 宮島 徹; 長井 惇; 森木 朝子; 松川 敏大; 荒 隆英; 後藤 秀樹; 豊嶋 崇徳
  日本エイズ学会誌, 26, 4, 459, 459, (一社)日本エイズ学会, Nov. 2024
  Japanese
• Ph染色体陰性BCR::ABL1陽性急性白血病の頻度と臨床的特徴
  横山 翔大; 小野澤 真弘; 木村 弘幸; 荒 隆英; 長井 惇; 吉田 匠汰; 宮下 直樹; 松川 敏大; 平林 真介; 盛 暁生; 日高 大輔; 橋口 淳一; 若狭 健太郎; 井端 淳; 武田 紫; 重松 明男; 山本 聡; 藤本 勝也; 堤 豊; 石原 敏道; 酒井 基; 柿木 康孝; 小宅 達郎; 近藤 健; 豊嶋 崇徳
  日本血液学会学術集会, 86回, O1, 1, (一社)日本血液学会, Oct. 2024
  English
• HLA半合致移植を施行したShwachman-Diamond症候群(SDS)を背景とした急性骨髄性白血病
  塚本 しほり; 中川 雅夫; 小野澤 真弘; 南谷 泰仁; 小島 圭祐; 原田 知弥; 荒 隆英; 松川 敏大; 白鳥 聡一; 遠藤 知之; 豊嶋 崇徳
  臨床血液, 65, 10, 1329, 1329, (一社)日本血液学会-東京事務局, Oct. 2024
  Japanese
• Ph染色体陰性BCR::ABL1陽性急性白血病の頻度と臨床的特徴
  横山 翔大; 小野澤 真弘; 木村 弘幸; 荒 隆英; 長井 惇; 吉田 匠汰; 宮下 直樹; 松川 敏大; 平林 真介; 盛 暁生; 日高 大輔; 橋口 淳一; 若狭 健太郎; 井端 淳; 武田 紫; 重松 明男; 山本 聡; 藤本 勝也; 堤 豊; 石原 敏道; 酒井 基; 柿木 康孝; 小宅 達郎; 近藤 健; 豊嶋 崇徳
  日本血液学会学術集会, 86回, O1, 1, (一社)日本血液学会, Oct. 2024
  English
• HIV陽性者における性感染症の実態
  松川 敏大; 遠藤 知之; 長井 惇; 宮島 徹; 須藤 啓斗; 長谷川 祐太; 荒 隆英; 後藤 秀樹; 豊嶋 崇徳
  日本エイズ学会誌, 26, 3, 132, 138, (一社)日本エイズ学会, Aug. 2024
  Japanese
• 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, 21 Jun. 2024, [International Magazine]
  English, Scientific journal, 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.
• A Nationwide Retrospective Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Adult Hemophagocytic Lymphohistiocytosis
  Haryoon Kim; Kota Mizuno; Kyoko Masuda; Masatoshi Sakurai; Takahide Ara; Kensuke Naito; Yasufumi Uehara; Go Yamamoto; Makoto Osada; Shinichiro Machida; Tomohiro Horio; Kentaro Fukushima; Yasuo Mori; Tatsuo Ichinohe; Takahiro Fukuda; Yoshiko Atsuta; Keisuke Kataoka
  Transplantation and Cellular Therapy, 30, 4, 419.e1, 419.e12, Elsevier BV, Apr. 2024, [Peer-reviewed]
  Scientific journal
• R-Spondin1 protects gastric stem cells and mitigates gastric GVHD in allogeneic hematopoietic stem cell transplantation.
  Eiko Hayase; Takahide Ara; Yumika Saito; Shuichiro Takahashi; Kosuke Yoshioka; Hiroyuki Ohigashi; Reiki Ogasawara; Emi Yokoyama; Tomohiro Yamakawa; Ko Ebata; Yuta Hasegawa; Kazuma Tomizuka; Takanori Teshima
  Blood advances, 8, 3, 725, 731, 13 Feb. 2024, [International Magazine]
  English, Scientific journal, Graft-versus-host disease (GVHD) is the major obstacle to performing allogeneic hematopoietic cell transplantation (allo-HCT). We and others have shown that intestinal stem cells are targeted in lower gastrointestinal GVHD. A leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)-expressing gastric stem cells (GSCs) reside at the base of the gastric glands in mice. After experimental allo-HCT, Lgr5+ GSCs significantly decreased. Parietal cells, which underwent continuous renewal by GSCs, were injured in gastric GVHD, leading to failure of gastric acidification and aerobic bacterial overgrowth in the duodenum. Fate-mapping analysis demonstrated that administration of R-Spondin1 (R-Spo1) that binds to Lgr5 for 6 days in naïve mice significantly increased proliferating epithelial cells derived from Lgr5+ GSCs. R-Spo1 administered on days -3 to -1 and from days +1 to +3 of allo-HCT protected GSCs, leading to amelioration of gastric GVHD and restoration of gastric acidification, and suppression of aerobic bacterial overgrowth in the duodenum. In conclusion, Lgr5+ GSCs were targeted by gastric GVHD, resulting in disruption of the gastric homeostasis, whereas R-Spo1 protected Lgr5+ GSCs from GVHD and maintained homeostasis in the stomach.
• HLA haploidentical stem cell transplantation from HLA homozygous donors to HLA heterozygous donors may have lower survival rates than haploidentical transplantation from HLA heterozygous donors to HLA heterozygous donors: a retrospective nationwide analysis.
  Keiko Fukunaga; Kazuhiro Ikegame; Hirohisa Nakamae; Noriko Doki; Takahiro Fukuda; Yukio Kondo; Takahide Ara; Tetsuya Eto; Yasuo Mori; Ken-Ichi Matsuoka; Yoshinobu Kanda; Makoto Onizuka; Yoshiko Atsuta; Tatsuo Ichinohe; Satoko Morishima; Junya Kanda
  International journal of hematology, 119, 2, 173, 182, Feb. 2024, [Domestic magazines]
  English, Scientific journal, In HLA haploidentical stem cell transplantation, patients and donors usually share one HLA haplotype and have one different HLA haplotype (hetero-to-hetero). However, there are rare cases of transplantation from HLA homozygous donors to heterozygous recipients (homo-to-hetero), resulting in mismatches only in the graft-versus-host direction. We previously reported that homo-to-hetero transplants have a lower survival rate in a mouse model than hetero-to-hetero transplants due to stronger graft-versus-host disease (GVHD) but inferior graft-versus-leukemia effect. To examine whether homo-to-hetero transplant effects also occur in humans, we retrospectively compared the results of 59 homo-to-hetero and 4,539 hetero-to-hetero cases in the Japanese transplant registry data. The results showed no statistical difference between the homo-to-hetero and hetero-to-hetero groups in the cumulative incidences of neutrophil engraftment (83.1% vs 89.0%), acute GVHD II-IV (36.8% vs 38.8%), III-IV (16.8% vs 17.4%), chronic GVHD (32.7% vs 30.7%), relapse (52.9% vs 49.0%), and non-relapse mortality (31.6% vs 28.2%). In contrast, overall survival was significantly lower in the homo-to-hetero group than in the hetero-to-hetero group (12.6% vs 26.2%, p = 0.0308). The inferior effect of homo-to-hetero transplantation on overall survival remained significant in multivariate analyses.
• Outcomes of allogeneic hematopoietic cell transplantation under letermovir prophylaxis for cytomegalovirus infection.
  Katsuto Takenaka; Shigeo Fuji; Toshihiro Matsukawa; Naoyuki Uchida; Takeshi Kobayashi; Masatsugu Tanaka; Takahide Ara; Kazuhiro Ikegame; Yukiyasu Ozawa; Yoshinobu Kanda; Masashi Sawa; Yumiko Maruyama; Takahiro Fukuda; Hirohisa Nakamae; Takafumi Kimura; Masao Ogata; Sachiko Seo; Yoshiko Atsuta; Keitaro Matsuo; Hideki Nakasone
  Annals of hematology, 103, 1, 285, 296, Jan. 2024, [International Magazine]
  English, Scientific journal, Cytomegalovirus (CMV) infection is a major infectious complication following allogeneic hematopoietic cell transplantation (allo-HCT). Although letermovir (LMV) prophylaxis dramatically reduces the incidence of early clinically significant CMV (csCMV) infection, it remains unclear whether it has a beneficial effect on nonrelapse mortality (NRM) and overall survival (OS). Herein, we evaluated the impact of LMV prophylaxis on posttransplant outcomes using the registry database of the Japanese Society for Transplantation and Cellular Therapy. Adult patients who underwent allo-HCT between 2017 and 2019 were analyzed (n = 6004). LMV prophylaxis was administered to 1640 patients (LMV group) and it significantly reduced the incidence of csCMV infection compared with those not administered LMV prophylaxis (15.4% vs 54.1%; p < 0.01). However, it did not improve the 1-year NRM (hazard ratio [HR], 0.93; p = 0.40) and OS (HR, 0.96; p = 0.49). In the LMV group, 74 patients had breakthrough csCMV infection and showed inferior NRM (HR, 3.44; p < 0.01) and OS (HR, 1.93; p = 0.02) compared with those without infection. After completing LMV prophylaxis, 252 patients had late csCMV infection and showed inferior NRM (HR, 1.83; p < 0.01) and OS (HR, 1.58; p < 0.01). Our findings suggest that managing breakthrough and late csCMV infections is important for improving long-term outcomes.
• Efficacy and Safety of Single-dose Pegfilgrastim for CD34+ Cell Mobilization in Healthy Volunteers: A Phase 2 Study.
  Hideki Goto; Junichi Sugita; Yuta Hasegawa; Koji Hayasaka; Kana Sunagoya; Rie Hatase; Mutsumi Nishida; Yuki Ichihashi; Mitsuhiko Odera; Hajime Senjo; Shota Yokoyama; Takahide Ara; Souichi Shiratori; Tomoyuki Endo; Masayuki Hino; Yoshinobu Maeda; Masashi Sawa; Norihiro Sato; Takanori Teshima
  Transplantation, 28 Nov. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers. METHODS: The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 106/L cluster of differentiation 34 positive (CD34+) cells. RESULTS: Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34+ cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34+ mobilization was achieved in all 23 subjects. The mean peripheral blood CD34+ cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation. CONCLUSIONS: A single-dose pegfilgrastim successfully mobilized an optimal number of CD34+ cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).
• HIV陽性者における性感染症の実態
  松川 敏大; 遠藤 知之; 長井 惇; 宮島 徹; 須藤 啓斗; 長谷川 祐太; 荒 隆英; 後藤 秀樹; 豊嶋 崇徳
  日本エイズ学会誌, 25, 4, 441, 441, (一社)日本エイズ学会, Nov. 2023
  Japanese
• 2剤療法施行中のHIV陽性者におけるBlipおよびTND(Target Not Detected)維持率の検討
  遠藤 知之; 後藤 秀樹; 松川 敏大; 荒 隆英; 長谷川 祐太; 須藤 啓斗; 宮島 徹; 長井 惇; 豊嶋 崇徳
  日本エイズ学会誌, 25, 4, 498, 498, (一社)日本エイズ学会, Nov. 2023
  Japanese
• Impact of GVHD on lymphoma progression: Nationwide study from Japanese Society for Transplantation and Cellular Therapy.
  Mizuki Watanabe; Junya Kanda; Takahiro Fukuda; Naoyuki Uchida; Kazuhiro Ikegame; Keisuke Kataoka; Hikaru Kobayashi; Takahide Ara; Jun Ishikawa; Ken-Ichi Matsuoka; Yasuhiro Sugio; Hideyuki Nakazawa; Takashi Ikeda; Yoshiko Atsuta; Eisei Kondo; Ritsuro Suzuki
  British journal of haematology, 203, 3, 446, 459, Nov. 2023, [International Magazine]
  English, Scientific journal, The graft-versus-lymphoma (GVL) effect and its association with acute and chronic GVHD (aGVHD, cGVHD) has not been comprehensively elucidated. We retrospectively analysed 2204 Japanese patients with non-Hodgkin lymphomas (NHLs; indolent B-NHLs, n = 689; aggressive B-NHLs, n = 720; mature T/NK-NHLs, n = 795) receiving a first allo-HSCT in 2003-2017. Pre-transplant lymphoma control showed complete response (CR) in 759 and non-CR in 1445. We assessed the impact of aGVHD/cGVHD on lymphoma progression and other outcomes. Although aGVHD/cGVHD showed no statistical impact on lymphoma progression in the overall cohort, their impact was clear in certain groups: Grade I-II aGVHD in CR patients (HR, 0.63; 95% CI, 0.43-0.91), especially in mature T/NK-NHL (HR, 0.46; 95% CI, 0.26-0.83) and extensive cGVHD in patients with mature aggressive B-NHLs (HR, 0.55; 95% CI, 0.31-0.97). In total, limited cGVHD was associated with superior survivals (progression-free survival: HR, 0.71; 95% CI, 0.56-0.90), whereas severe GVHDs showed negative impacts on them. Our results support the presence of GVL effects differentially associated with GVHD in different lymphoma subtypes/controls. Meanwhile, it was also suggested that we should manage GVHDs within a limited activity, considering the negative impact of severe GVHDs. As pre-transplant lymphoma control remains a strong factor influencing transplant outcomes, improving its management is an important issue to be addressed.
• 急性骨髄性白血病における移植後シクロホスファミドを用いたハプロ移植の予後因子解析
  柴田 翔; 新井 康之; 近藤 忠一; 山崎 聡; 水野 昌平; 中前 博久; 荒 隆英; 衛藤 徹也; 長藤 宏司; 鬼塚 真仁; 福田 隆浩; 熱田 由子; 柳田 正光
  日本血液学会学術集会, 85回, 166, 166, (一社)日本血液学会, Oct. 2023
  English
• 移植前呼吸機能低下を伴うHLA適合同種造血細胞移植における至適ドナーソースの検討
  川村 俊人; 玉置 雅治; 小沼 貴晶; 鬼塚 真仁; 堺田 恵美子; 林 裕美; 土岐 典子; 小澤 幸泰; 澤 正史; 荒 隆英; 福田 隆浩; 一戸 辰夫; 熱田 由子; 神田 善伸; 藥師神 公和; 諫田 淳也; 仲宗根 秀樹
  日本血液学会学術集会, 85回, 170, 170, (一社)日本血液学会, Oct. 2023
  English
• 急性骨髄性白血病における同種移植前処置強度スコアの外部検証
  柳田 正光; 下村 良充; 水野 昌平; 松田 健佑; 近藤 忠一; 土岐 典子; 田中 正嗣; 福田 隆浩; 荒 隆英; 内田 直之; 鬼塚 真仁; 澤 正史; 小澤 幸泰; 平本 展大; 太田 秀一; 諫田 淳也; 神田 善伸; 一戸 辰夫; 岡本 真一郎; 熱田 由子; 小沼 貴晶
  日本血液学会学術集会, 85回, 963, 963, (一社)日本血液学会, Oct. 2023
  English
• 移植前肝臓合併症患者における同種移植の予後と合併症
  三崎 柚季子; 玉置 雅治; 柳沢 龍; 土岐 典子; 福田 隆浩; 内田 直之; 田中 正嗣; 小澤 幸泰; 澤 正史; 荒 隆英; 諫田 淳也; 熱田 由子; 神田 善伸; 仲宗根 秀樹
  日本血液学会学術集会, 85回, 686, 686, (一社)日本血液学会, Oct. 2023
  English
• Improved long-term net survival after allogeneic hematopoietic cell transplantation in patients with hematologic malignancies over two decades.
  Marie Ohbiki; Yuri Ito; Yoshihiro Inamoto; Koichi Miyamura; Naoyuki Uchida; Takahiro Fukuda; Hiroki Fujiwara; Tetsuya Nishida; Masayasu Hayashi; Masatsugu Tanaka; Toshiro Kawakita; Kazuhiro Ikegame; Yuta Katayama; Takahide Ara; Tatsuo Ichinohe; Hitoshi Kiyoi; Keitaro Matsuo; Yoshiko Atsuta
  Transplantation and cellular therapy, 20 Sep. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: Allogeneic (allo-) hematopoietic cell transplantation (HCT) has evolved as a curative therapy for hematologic malignancies and diseases, with practice changes over the past two decades. OBJECTIVE: This study aimed to evaluate the change in 5-year net survival (NS) of allo-HCT recipients in a population-based cohort over the past two decades, which allows the estimation of a more HCT-specific long-term survival rate by considering background mortality changes. STUDY DESIGN: This study included 42,064 patients with hematologic malignancies who underwent their first allo-HCT in Japan from 2000 to 2018 and were reported to the Transplant Registry Unified Management Program. We compared the 5-year NS after allo-HCT in four consecutive HCT periods (2000-2004, 2005-2008, 2009-2012, and 2013-2018). Five-year NS of the latest period was estimated using the period analysis method. Adjusted excess hazard ratios for 5-year NS over the HCT period were analyzed using an excess hazard model. In addition to the analysis of all hematologic malignancies, adjusted 5-year NS for each major hematologic malignancy, including acute myelogenous leukemia, acute lymphoblastic leukemia (ALL), myelodysplastic syndrome, adult T-cell leukemia/lymphoma, chronic myeloid leukemia (CML), and malignant lymphoma, was analyzed. RESULTS: The probability of adjusted 5-year NS after HCT significantly improved over time: 35% in 2000-2004, 39% in 2005-2008, 45% in 2009-2012, and 49% in 2013-2018. The adjusted excess hazard ratios were 0.90 (95% confidence interval [CI], 0.86-0.93) in the 2005-2008 period, 0.77 (95% CI, 0.74-0.80) in the 2009-2012 period, and 0.65 (95% CI, 0.63-0.68) in the 2013-2018 period, respectively, with the 2000-2004 period as the reference. Five-year NS improved among all hematologic malignancies, with a significant improvement in CML and ALL. The changes in 5-year NS from the 2000-2004 period to the 2013-2018 period ranged from 46% to 66% in CML and from 41% to 59% in ALL. In addition to the large improvement of 1-year NS, smaller, but continued improvement of NS between 1 and 5 years after transplantation was observed. Net survival at five years conditional on being alive at one year increased from 64% in 2000-2004 to 73% in 2013-2018. CONCLUSION: Even after subtracting the background mortality in the general population, we found a significant improvement in long-term allo-HCT-specific survival rates for patients with hematologic malignancies over the past two decades in Japan.
• 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, 05 Sep. 2023, [International Magazine]
  English
• Risk factors and outcome of Stenotrophomonas maltophilia infection after allogeneic hematopoietic stem cell transplantation: JSTCT, Transplant Complications Working Group.
  Masuho Saburi; Kumi Oshima; Kuniko Takano; Yoshitaka Inoue; Kaito Harada; Naoyuki Uchida; Takahiro Fukuda; Noriko Doki; Kazuhiro Ikegame; Yayoi Matsuo; Yuta Katayama; Yukiyasu Ozawa; Ken-Ichi Matsuoka; Toshiro Kawakita; Yasuo Mori; Takahide Ara; Hirohisa Nakamae; Takafumi Kimura; Yoshinobu Kanda; Yoshiko Atsuta; Masao Ogata
  Annals of hematology, 102, 9, 2507, 2516, Sep. 2023, [International Magazine]
  English, Scientific journal, Stenotrophomonas maltophilia (S. maltophilia) is an aerobic nonfermenting Gram-negative bacillus widely distributed in the environment that has inherent multidrug resistance to beta-lactam and carbapenem antibiotics. S. maltophilia infection (SMI) is known as an important fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT), but its clinical characteristics have not been well clarified. A retrospective study to identify the incidence, risk factors, and outcomes of SMI after allogeneic HSCT was performed using the database of the Japanese nationwide registry, including 29,052 patients who received allogeneic HSCT in Japan between January 2007 and December 2016. A total of 665 patients developed SMI (sepsis/septic shock, 432; pneumonia, 171; other, 62). The cumulative incidence of SMI at 100 days after HSCT was 2.2%. Among risk factors identified for SMI (age ≥ 50 years, male, performance status 2-4, cord blood transplantation [CBT], myeloablative conditioning, Hematopoietic Cell Transplant-Comorbidity Index [HCT-CI] score 1-2, HCT-CI score ≥ 3, and active infectious disease at HSCT), CBT was the strongest risk factor (hazard ratio, 2.89; 95%CI, 1.94-4.32; p < 0.001). The survival rate at day 30 after SMI was 45.7%, and SMI before neutrophil engraftment was significantly associated with poor survival (survival rate 30 days after SMI, 40.1% and 53.8% in patients with SMI before and after engraftment, respectively; p = 0.002). SMI is rare after allogeneic HSCT, but its prognosis is extremely poor. CBT was a strong risk factor for SMI, and its development prior to neutrophil engraftment was associated with poor survival.
• Impact of HLA disparity on overall mortality risk in patients with extensive chronic GVHD: The HLA Working Group of Japanese Society for Transplantation and Cellular Therapy.
  Shigeo Fuji; Akitoshi Hakoda; Junya Kanda; Takahiro Fukuda; Noriko Doki; Yuta Katayama; Naoyuki Uchida; Yukiyasu Ozawa; Yoshinobu Kanda; Masatsugu Tanaka; Keisuke Kataoka; Takahide Ara; Masashi Sawa; Makoto Onizuka; Yasushi Onishi; Takafumi Kimura; Tatsuo Ichinohe; Yoshiko Atsuta; Ayumi Shintani; Satoko Morishima
  Bone marrow transplantation, 07 Aug. 2023, [International Magazine]
  English
• External validation and extended application of the transplant conditioning intensity score in acute myeloid leukemia.
  Masamitsu Yanada; Yoshimitsu Shimomura; Shohei Mizuno; Kensuke Matsuda; Tadakazu Kondo; Noriko Doki; Masatsugu Tanaka; Takahiro Fukuda; Takahide Ara; Naoyuki Uchida; Makoto Onizuka; Masashi Sawa; Yukiyasu Ozawa; Nobuhiro Hiramoto; Shuichi Ota; Junya Kanda; Yoshinobu Kanda; Tatsuo Ichinohe; Shinichiro Okamoto; Yoshiko Atsuta; Takaaki Konuma
  Bone marrow transplantation, 58, 10, 1096, 1103, 13 Jul. 2023, [International Magazine]
  English, Scientific journal, This study aimed to validate the utility of the transplant conditioning intensity (TCI) score in 1714 patients with acute myeloid leukemia (AML) undergoing allogeneic bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT) and assess its applicability to 753 patients with AML undergoing umbilical cord blood transplantation (UCBT) both during first complete remission. Patients classified into a high TCI group accounted for 63% and 56% in the BMT/PBSCT and UCBT cohorts, respectively. In the BMT/PBSCT cohort, the risk of relapse was lower in patients in the high versus intermediate TCI group (P = 0.002), although non-relapse mortality (NRM) did not differ among the three TCI groups. In the UCBT cohort, both relapse and NRM did not differ among the TCI groups. Increasing cutoff points for intermediate and high TCI categories significantly improved the ability to predict relapse and NRM in the BMT/PBSCT cohort (P = 0.030 and 0.006, respectively), and relapse but not NRM in the UCBT cohort (P = 0.005 and 0.364, respectively). These findings highlight the difference in the threshold level of the TCI score for outcome discrimination between European and Japanese cohorts. The TCI scheme appears less effective for UCBT than for BMT/PBSCT.
• 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, 22 May 2023, [International Magazine]
  English, Scientific journal, 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.
• Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach
  Tomoyasu Jo; Yasuyuki Arai; Shinichiro Oshima; Tadakazu Kondo; Kaito Harada; Naoyuki Uchida; Noriko Doki; Takahiro Fukuda; Masatsugu Tanaka; Yukiyasu Ozawa; Takuro Kuriyama; Kazuhiro Ikegame; Yuta Katayama; Shuichi Ota; Takahide Ara; Toshiro Kawakita; Makoto Onizuka; Tatsuo Ichinohe; Yoshiko Atsuta; Masamitsu Yanada
  British Journal of Haematology, Wiley, 21 May 2023
  Scientific journal
• A convolutional neural network-based model that predicts acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
  Tomoyasu Jo; Yasuyuki Arai; Junya Kanda; Tadakazu Kondo; Kazuhiro Ikegame; Naoyuki Uchida; Noriko Doki; Takahiro Fukuda; Yukiyasu Ozawa; Masatsugu Tanaka; Takahide Ara; Takuro Kuriyama; Yuta Katayama; Toshiro Kawakita; Yoshinobu Kanda; Makoto Onizuka; Tatsuo Ichinohe; Yoshiko Atsuta; Seitaro Terakura
  Communications Medicine, 3, 1, Springer Science and Business Media LLC, 16 May 2023
  Scientific journal, Abstract
  
  Background
  
  Forecasting acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is highly challenging with conventional statistical techniques due to complex parameters and their interactions. The primary object of this study was to establish a convolutional neural network (CNN)-based prediction model for aGVHD.
  
  Method
  
  We analyzed adult patients who underwent allogeneic HSCT between 2008 and 2018, using the Japanese nationwide registry database. The CNN algorithm, equipped with a natural language processing technique and an interpretable explanation algorithm, was applied to develop and validate prediction models.
  
  Results
  
  Here, we evaluate 18,763 patients between 16 and 80 years of age (median, 50 years). In total, grade II–IV and grade III–IV aGVHD is observed among 42.0% and 15.6%. The CNN-based model eventually allows us to calculate a prediction score of aGVHD for an individual case, which is validated to distinguish the high-risk group of aGVHD in the test cohort: cumulative incidence of grade III–IV aGVHD at Day 100 after HSCT is 28.8% for patients assigned to a high-risk group by the CNN model, compared to 8.4% among low-risk patients (hazard ratio, 4.02; 95% confidence interval, 2.70–5.97; p < 0.01), suggesting high generalizability. Furthermore, our CNN-based model succeeds in visualizing the learning process. Moreover, contributions of pre-transplant parameters other than HLA information to the risk of aGVHD are determined.
  
  Conclusions
  
  Our results suggest that CNN-based prediction provides a faithful prediction model for aGVHD, and can serve as a valuable tool for decision-making in clinical practice.
• Allogeneic stem cell transplantation for children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia in the tyrosine kinase inhibitor era.
  Hisashi Ishida; Hiroyuki Shimada; Akihiko Tanizawa; Yutaka Shimazu; Takayoshi Tachibana; Noriko Doki; Takahide Ara; Yayoi Matsuo; Miho Nara; Tomomi Toubai; Kazuko Ino; Hirohisa Nakamae; Keisuke Kato; Koji Kato; Atsushi Sato; Moeko Hino; Kimikazu Matsumoto; Yoshiko Atsuta; Masahiro Yasui; Tokiko Nagamura-Inoue
  American journal of hematology, 12 May 2023, [International Magazine]
  English, The analysis of 165 children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia showed disease status at hematopoietic stem cell transplantation was a strong prognostic factor and clearly separated the patient outcomes.
• Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group.
  Shun-Ichi Kimura; Yu Akahoshi; Souichi Shiratori; Keiji Okinaka; Kaito Harada; Naoyuki Uchida; Noriko Doki; Kazuhiro Ikegame; Hirohisa Nakamae; Masatsugu Tanaka; Satoru Takada; Toshiro Kawakita; Ken-Ichi Matsuoka; Takahide Ara; Shuichi Ota; Masashi Sawa; Makoto Onizuka; Takahiro Fukuda; Yoshiko Atsuta; Yoshinobu Kanda; Hideki Nakasone
  Open forum infectious diseases, 10, 4, ofad163, Apr. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients. METHODS: Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019. RESULTS: Noninfectious IP was observed in 694 patients at a median (range) of 63 (0-1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0-903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48-4.25), along with total body irradiation (>8 Gy; HR, 1.57; 95% CI, 1.18-2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004-1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45-0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49-0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P < .001). CONCLUSIONS: Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.
• Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical relatives in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia: a propensity score analysis of a nationwide database.
  Hidehiro Itonaga; Yasushi Miyazaki; Kazunari Aoki; Naoki Shingai; Yukiyasu Ozawa; Takahiro Fukuda; Keisuke Kataoka; Toshiro Kawakita; Yasunori Ueda; Takahide Ara; Masatsugu Tanaka; Yuta Katayama; Masashi Sawa; Tetsuya Eto; Junya Kanda; Yoshiko Atsuta; Ken Ishiyama
  Annals of hematology, 15 Mar. 2023, [International Magazine]
  English, Scientific journal, Bone marrow (BM) and granulocyte colony-stimulating factor-mobilized peripheral blood stem cells (PBSC) are used as grafts from HLA-identical-related donors for adults with myelodysplastic syndrome (MDS). To assess the impact of graft sources on post-transplant outcomes in MDS patients, we conducted a retrospective analysis of a nationwide database. A total of 247 and 280 patients underwent transplantation with BM and PBSC, respectively. The inverse probability of treatment weighting (IPTW) methods revealed that overall survival (OS) was comparable between BM and PBSC (P = .129), but PBSC transplantation was associated with worse graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) (hazard rate [HR], 1.24; 95% confidence intervals [CIs], 1.00-1.53; P = 0.049) and chronic GVHD-free and relapse-free survival (CRFS) (HR, 1.29; 95% CIs, 1.13-1.73; P = 0.002) than BM transplantation. In the propensity score matched cohort (BM, n = 216; PBSC, n = 216), no significant differences were observed in OS and relapse; 3-year OS rates were 64.7% and 60.0% (P = 0.107), while 3-year relapse rates were 27.1% and 23.5% (P = 0.255) in BM and PBSC, respectively. Three-year GRFS rates (36.6% vs. 29.2%; P = 0.006), CRFS rate (37.7% vs. 32.5%; P = 0.003), and non-relapse mortality rates (13.9% vs. 21.1%; P = 0.020) were better in BM than in PBSC. The present study showed that BM transplantation provides a comparable survival benefit with PBSC transplantation and did not identify an enhanced graft-versus-MDS effect to reduce the incidence of relapse in PBSC transplantation.
• Effect of graft-versus-host disease on posttransplant outcomes following single cord blood transplantation in comparison to haploidentical transplantation with posttransplant cyclophosphamide for adult acute myeloid leukemia.
  Takaaki Konuma; Kensuke Matsuda; Yoshimitsu Shimomura; Susumu Tanoue; Junichi Sugita; Yoshihiro Inamoto; Masahiro Hirayama; Takahide Ara; Hirohisa Nakamae; Shuichi Ota; Yumiko Maruyama; Tetsuya Eto; Naoyuki Uchida; Masatsugu Tanaka; Kazuya Ishiwata; Satoshi Koi; Satoshi Takahashi; Yukiyasu Ozawa; Makoto Onizuka; Yoshinobu Kanda; Takafumi Kimura; Tatsuo Ichinohe; Yoshiko Atsuta; Junya Kanda; Masamitsu Yanada
  Transplantation and cellular therapy, 06 Mar. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: The possibility that human leukocyte antigen (HLA) mismatches could reduce relapse after alternative HLA-mismatched allogeneic hematopoietic cell transplantation (HCT) is an attractive concept for acute myeloid leukemia (AML). However, it remains unclear whether the prognostic effect of graft-versus-host disease (GVHD) on survival differs between single-unit cord blood transplantation (CBT) or haploidentical HCT using posttransplant cyclophosphamide (PTCy-haplo HCT) for AML. OBJECTIVE: The objective of this retrospective study was to compare the effect of acute and chronic GVHD on posttransplant outcomes between CBT and PTCy-haplo HCT. STUDY DESIGN: We retrospectively evaluated the effect of acute and chronic GVHD on posttransplant outcomes following CBT and PTCy-haplo HCT in adults with AML (n=1,981) between 2014 and 2020 using a Japanese registry database. RESULTS: In the univariate analysis, the probability of overall survival was significantly greater in patients who developed grade I-II acute GVHD (P<0.001 by log-rank test) and limited chronic GVHD (P<0.001 by log-rank test) among CBT recipients, but these effects were not significant among PTCy-haplo HCT recipients. In the multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, the effect of grade I-II acute GVHD on reducing overall mortality was significant between CBT and PTCy-haplo HCT (adjusted hazard ratio [HR] for CBT: 0.73, 95% confidence interval [CI]: 0.60-0.87; adjusted HR for PTCy-haplo HCT: 1.07, 95% CI: 0.70-1.64; p for interaction=0.038). CONCLUSION: Our data demonstrate that grade I-II acute GVHD was associated with a significant improvement in overall mortality in adults with AML receiving CBT but not PTCy-haplo HCT.
• Fludarabine plus reduced-intensity busulfan versus fludarabine plus myeloablative busulfan in patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic cell transplantation.
  Kimimori Kamijo; Yoshimitsu Shimomura; Akihito Shinohara; Shohei Mizuno; Minoru Kanaya; Yoshiaki Usui; Sung-Won Kim; Takahide Ara; Ishikazu Mizuno; Takuro Kuriyama; Hideyuki Nakazawa; Ken-Ichi Matsuoka; Shigeru Kusumoto; Nobuo Maseki; Masaki Yamaguchi; Takashi Ashida; Makoto Onizuka; Takahiro Fukuda; Yoshiko Atsuta; Eisei Kondo
  Annals of hematology, 102, 3, 651, 661, Mar. 2023, [International Magazine]
  English, Scientific journal, Allogeneic hematopoietic cell transplantation (HCT) offers a possible cure for patients with relapsed and refractory non-Hodgkin lymphoma (NHL) through potentially beneficial graft versus lymphoma effects. However, allogeneic HCT is associated with high nonrelapse mortality (NRM). Fludarabine with reduced-intensity busulfan (Flu/Bu2) and myeloablative busulfan (Flu/Bu4) are commonly used in conditioning regimens for allogeneic HCT; however, data on their use in patients with NHL is limited. We investigated the effect of busulfan dose on outcomes by comparing Flu/Bu2 and Flu/Bu4 in patients with NHL who underwent allogeneic HCT. Our study included 415 adult patients with NHL who received Flu/Bu2 (315 patients) or Flu/Bu4 (100 patients) between January 2008 and December 2019. All patients were enrolled in the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. The primary endpoint was the 5-year overall survival (OS). To minimize potential confounding factors that may influence outcomes, we performed propensity score matching. The 5-year OS was 50.6% (95% confidence interval (CI), 39.4%-60.8%) and 32.2% (95% CI, 22.4-42.4%) in the Flu/Bu2 and Flu/Bu4 groups, respectively (p = 0.006). The hazard ratio comparing the two groups was 2.13 (95% CI, 1.30-3.50; p = 0.003). Both groups had a similar 5-year cumulative incidence of relapse (38.2% vs 41.3%; p = 0.581), and the Flu/Bu4 group had a higher cumulative incidence of 5-year NRM (15.7% vs 31.9%; p = 0.043). In this study, Flu/Bu4 was associated with worse OS compared with Flu/Bu2 because of high NRM in patients with NHL.
• CMV reactivation after allogeneic HCT is associated with a reduced risk of relapse in acute lymphoblastic leukemia.
  Yu Akahoshi; Hideki Nakasone; Katsuto Takenaka; Satoshi Yamasaki; Momoko Nakamura; Noriko Doki; Masatsugu Tanaka; Yukiyasu Ozawa; Naoyuki Uchida; Takahide Ara; Hirohisa Nakamae; Shuichi Ota; Makoto Onizuka; Shingo Yano; Junji Tanaka; Takahiro Fukuda; Yoshinobu Kanda; Yoshiko Atsuta; Shinichi Kako; Masamitsu Yanada; Yasuyuki Arai
  Blood advances, 20 Jan. 2023, [International Magazine]
  English, Scientific journal, Cytomegalovirus reactivation (CMVR) after allogeneic hematopoietic cell transplantation (HCT) is a frequent complication related to survival outcomes, but the impact of CMVR on relapse is still unclear, especially in acute lymphoblastic leukemia (ALL). In this nationwide retrospective study, we included patients with acute myeloid leukemia (AML) and ALL in first or second complete remission who underwent their first HCT using pre-emptive strategy for CMVR. Because ninety percent of cases with CMVR had occurred by day 64 and ninety percent of cases with grades II to IV acute GVHD had occurred by day 58, a landmark point was set at day 65. In the landmark analyses, 3793 patients with AML and 2213 patients with ALL who survived without relapse for at least 65 days were analyzed. In the multivariate analyses, CMVR was associated with a lower incidence of relapse in both AML (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.95; P = 0.009) and ALL (HR, 0.81; 95% CI, 0.66-0.99; P = 0.045). These findings were confirmed when we treated CMVR as a time-dependent covariate. Moreover, our study suggested that the protective effect of CMVR on relapse was independent of acute GVHD. A post-hoc subgroup analysis that combined AML and ALL showed that CMVR had a mild anti-leukemia effect without effect modification in contrast to the impact of CMVR on NRM. Our findings may provide important implications for the strategy used for CMV prophylaxis after HCT.
• Progress in survival following three decades of allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: a real-world registry study in Japan.
  Takaaki Konuma; Hidehiro Itonaga; Ken Ishiyama; Atsushi Hamamura; Naoyuki Uchida; Yukiyasu Ozawa; Yuta Katayama; Masatoshi Sakurai; Yasunori Ueda; Ken-Ichi Matsuoka; Toshiro Kawakita; Tetsuya Eto; Takahide Ara; Junya Kanda; Onizuka Makoto; Takahiro Fukuda; Yoshiko Atsuta
  American journal of hematology, 98, 4, E68-E71, 12 Jan. 2023, [International Magazine]
  English
• Effect of the COVID-19 pandemic on allogeneic stem cell transplantation in Japan.
  Yoshimitsu Shimomura; Tetsuhisa Kitamura; Masashi Nishikubo; Tomotaka Sobue; Naoyuki Uchida; Noriko Doki; Masatsugu Tanaka; Ayumu Ito; Jun Ishikawa; Takahide Ara; Shuichi Ota; Makoto Onizuka; Masashi Sawa; Yukiyasu Ozawa; Yumiko Maruyama; Kazuhiro Ikegame; Yoshinobu Kanda; Tatsuo Ichinohe; Takahiro Fukuda; Shinichiro Okamoto; Takanori Teshima; Yoshiko Atsuta
  International journal of hematology, 117, 4, 1, 8, 14 Dec. 2022, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, The coronavirus disease 2019 (COVID-19) pandemic affected healthcare quality and access worldwide and may also have negatively affected the frequency and outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated the effect of the pandemic on allogeneic HSCT in Japan. Our subjects were patients who received allogeneic HSCT during January 2018-December 2020 in Japan. We assessed differences in yearly number of allogeneic HSCTs and 1-year outcomes in 2020 versus both 2019 and 2018. The total number of patients who received allogeneic HSCT increased from 3621 patients in 2018 and 3708 patients in 2019 to 3865 patients in 2020. Some following changes in allogeneic HSCT methods were observed: patients were older, fewer patients received bone marrow transplantation, fewer patients received transplants from unrelated donors, fewer patients received transplants from matched donors, more patients received reduced-intensity conditioning, and fewer patients received anti-thymocyte globulin in 2020 compared with previous years. HSCT outcomes were not affected, as 1-year overall survival was not significantly different (65.8% in 2020, vs. 66.5% in 2019 and 66.4% in 2018). Our results suggest that we can maintain transplant care during the pandemic by controlling the spread of COVID-19 and modifying HSCT methods.
• 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, 29 Nov. 2022, [International Magazine]
  English, Scientific journal, 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.
• Severe short-term adverse events in related bone marrow or peripheral blood stem cell donors.
  Ryu Yanagisawa; Tsuneaki Hirakawa; Noriko Doki; Kazuhiro Ikegame; Ken-Ichi Matsuoka; Takahiro Fukuda; Hirohisa Nakamae; Shuichi Ota; Nobuhiro Hiramoto; Jun Ishikawa; Takahide Ara; Masatsugu Tanaka; Yuhki Koga; Toshiro Kawakita; Yumiko Maruyama; Yoshinobu Kanda; Masayuki Hino; Yoshiko Atsuta; Hiromasa Yabe; Nobuhiro Tsukada
  International journal of hematology, 20 Nov. 2022, [Domestic magazines]
  English, Scientific journal, The incidence of severe adverse events (SAEs) and associated risk factors in hematopoietic cell transplantation donors needs to be clarified for related donors (relatives of the transplant recipient), whose criteria for donation are more lenient than for unrelated donors. Data from related donors registered in the Japanese national data registry database between 2005 and 2021 were evaluated to determine the association of short-term SAE incidence with donor characteristics at registration.Fourteen of 4339 bone marrow (BM) donors (0.32%) and 54 of 10,684 peripheral blood stem cell (PBSC) donors (0.51%) experienced confirmed SAEs during the short donation period. No deaths were observed. Past medical history was a common risk factor for SAEs in both BM and PBSC donors. Age of 60 years or older and female sex were identified as risk factors for SAEs in PBSC donors. Female sex was also a risk factor for poor mobilization, which resulted in discontinuation of PBSC collection.Although donors should be selected carefully, a certain level of safety is ensured for related donors in Japan. Donor safety should be further increased by improving the selection method for related donors and extending the follow-up period.
• Risk factors for fatal cardiac complications after allogeneic hematopoietic cell transplantation: Japanese Society for Transplantation and Cellular Therapy transplant complications working group.
  Ryu Yanagisawa; Masaharu Tamaki; Reo Tanoshima; Yukiko Misaki; Naoyuki Uchida; Satoshi Koi; Takashi Tanaka; Yukiyasu Ozawa; Yayoi Matsuo; Masatsugu Tanaka; Kazuhiro Ikegame; Yuta Katayama; Ken-Ichi Matsuoka; Takahide Ara; Yoshinobu Kanda; Kimikazu Matsumoto; Takahiro Fukuda; Yoshiko Atsuta; Motohiro Kato; Hideki Nakasone
  Hematological oncology, 17 Nov. 2022, [International Magazine]
  English, Scientific journal, Fatal cardiac complications can occur from the early to late phases after hematopoietic cell transplantation (HCT). Herein, the Japanese transplant registry database was used to retrospectively analyze health records of 33,791 allogeneic HCT recipients to elucidate the pathogenesis and risk factors involved. Overall, 527 patients died of cardiac complications at a median of 130 (range 0-3924) days after HCT. The cumulative incidence of fatal cardiac complications was 1.2% (95% confidence interval [CI]: 1.0-1.3) and 1.6% (95% CI: 1.5-1.8) at 1 and 5 years after HCT, respectively. Fatal cardiovascular events were significantly associated with an HCT-specific comorbidity index (HCT-CI) score of ≥1 specific to the three cardiovascular items, lower performance status, conditioning regimen cyclophosphamide dose of >120 mg/kg, and female sex. Cardiovascular death risk within 60 days after HCT was associated with the type of conditioning regimen, presence of bacterial or fungal infections at HCT, and number of blood transfusions. Contrastingly, late cardiovascular death beyond 1 year after HCT was associated with female sex and older age. Lower performance status and positive cardiovascular disease-related HCT-CI were risk factors for cardiac complications in all phases after HCT. Systematic follow-up may be necessary according to the patients' risk factors and conditions.
• 大腿骨人工骨頭インプラント周囲に発症したALK陰性未分化大細胞型リンパ腫の1例
  森 祐斗; 荒 隆英; 中川 雅夫; 吉田 匠汰; 斎藤 祐美花; 横山 翔大; 松川 敏大; 白鳥 聡一; 遠藤 知之; 豊嶋 崇徳
  臨床血液, 63, 11, 1592, 1593, (一社)日本血液学会-東京事務局, Nov. 2022
  Japanese
• Intensified conditioning regimens improved disease-free survival and engraftment after unrelated single-unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation.
  Takaaki Konuma; Junya Kanda; Naoyuki Uchida; Akihiko Nishijima; Masatsugu Tanaka; Yukiyasu Ozawa; MasashiSawa; MakotoOnizuka; Shuichi Ota; Yumiko Maruyama; Yoshinobu Kanda; Toshiro Kawakita; Takahide Ara; Tetsuya Eto; Hirohisa Nakamae; Takafumi Kimura; Takahiro Fukuda; Yoshiko Atsuta; For The Donor/Source Working Group Of The Japanese Society For Transplantation; Cellular Therapy
  Hematological oncology, 21 Oct. 2022, [International Magazine]
  English, Scientific journal, The impact of conditioning intensity on different donor groups has been unclear in allogeneic transplantation. The objective of this study was to clarify the effect of conditioning intensity on disease-free survival (DFS), relapse, non-relapse mortality (NRM), neutrophil engraftment, and graft-versus-host disease (GVHD) for each donor type. We retrospectively evaluated the effect of conditioning intensity on transplant outcomes for adult patients with acute leukemia or myelodysplastic syndrome aged between 16 and 60 years in Japan using the transplant conditioning intensity (TCI) scoring system. A total of 8,526 patients who received first allogeneic transplantation from 6/6 antigen-matched sibling donor (MSD, n=2768), 8/8 allele-matched unrelated donor (MUD, n=2357), and unrelated single-cord blood (UCB, n=3401) were eligible for the analyses. Compared to conditioning with TCI score 4.0, which was corresponds to conventional myeloablative conditioning, including cyclophosphamide with total body irradiation 12 Gy or busulfan 12.8 mg, and was considered as the reference group in the multivariate analyses, intensified conditioning with TCI score ≥4.5 improved DFS (hazard ratio [HR],0.81, P<0.001) and relapse rate (HR,0.70, P<0.001) but only after UCB transplants and not MSD and MUD transplants. In contrast, NRM was higher after intensified conditioning with TCI score ≥4.5 for MSD (HR,1.39, P=0.008) and MUD (HR,1.47, P=0.002) transplants but not UCB transplants (HR,1.12, P=0.240). Neutrophil engraftment was also significantly higher after intensified conditioning with TCI score ≥4.5 but only for UCB transplants (HR,1.24, P<0.001), whereas it was significantly lower after reduced- intensity conditioning with TCI score ≤3.5 for MSD transplants only (HR,0.82, P<0.001). These data demonstrated that an intensified conditioning regimen improved survival and engraftment rate only after a UCB transplants. Therefore, TCI scoring system could enable the optimization of conditioning intensity according to donor type, particularly in terms of survival and engraftment. This article is protected by copyright. All rights reserved.
• The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation
  Shota Yoshida; Takahide Ara; Kohei Okada; Yuto Mori; Shihori Tsukamoto; Naoki Miyashita; Kohei Kasahara; Ko Ebata; Junko Iwasaki; Shojiro Takahashi; Akio Shigematsu; Koichiro Minauchi; Naoki Kobayashi; Masahiro Ogasawara; Masahiro Imamura; Takanori Teshima; Shuichi Ota
  Bone Marrow Transplantation, 58, 1, 97, 99, 15 Oct. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal
• CMV再活性化が移植後急性白血病再発に与える影響
  赤星 佑; 仲宗根 秀樹; 竹中 克斗; 山崎 聡; 中村 桃子; 土岐 典子; 田中 正嗣; 小澤 幸泰; 内田 直之; 荒 隆英; 中前 博久; 太田 秀一; 鬼塚 真仁; 矢野 真吾; 田中 淳司; 福田 隆浩; 神田 善伸; 熱田 由子; 賀古 真一; 柳田 正光; 新井 康之
  日本血液学会学術集会, 84回, 828, 828, (一社)日本血液学会, Oct. 2022
  English
• Antiretroviral therapy achieved metabolic complete remission of hepatic AIDS related Epstein-Barr virus-associated smooth muscle tumor.
  Takahide Ara; Tomoyuki Endo; Hideki Goto; Kohei Kasahara; Yuta Hasegawa; Shota Yokoyama; Souichi Shiratori; Masao Nakagawa; Ken Kuwahara; Emi Takakuwa; Satoshi Hashino; Takanori Teshima
  Antiviral therapy, 27, 5, 13596535221126828, 13596535221126828, Oct. 2022, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal, Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.
• Haploidentical transplantation with post-transplant cyclophosphamide versus single cord blood transplantation for myelodysplastic syndrome: A retrospective study from the Adult Myelodysplastic Syndrome Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT).
  Takaaki Konuma; Yoshimitsu Shimomura; Ken Ishiyama; Takahide Ara; Hirohisa Nakamae; Nobuhiro Hiramoto; Tetsuya Eto; Yumiko Maruyama; Koji Nagafuji; Jun Ishikawa; Naoyuki Uchida; Masatsugu Tanaka; Makoto Onizuka; Yasunori Ueda; Naoyuki Anzai; Takafumi Kimura; Yoshinobu Kanda; Takahiro Fukuda; Yoshiko Atsuta
  American journal of hematology, 97, 12, E447-E450, 11 Sep. 2022, [International Magazine]
  English
• Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas.
  Masahiro Chiba; Joji Shimono; Takashi Ishio; Norio Takei; Kohei Kasahara; Reiki Ogasawara; Takahide Ara; Hideki Goto; Koh Izumiyama; Satoko Otsuguro; Liyanage P Perera; Hiroo Hasegawa; Michiyuki Maeda; Satoshi Hashino; Katsumi Maenaka; Takanori Teshima; Thomas A Waldmann; Yibin Yang; Masao Nakagawa
  Blood, 140, 18, 1951, 1963, 03 Aug. 2022, [International Magazine]
  English, Scientific journal, Adult T-cell leukemia/lymphoma (ATLL) is one of the aggressive peripheral T-cell neoplasms with a poor prognosis. Accumulating evidence demonstrates that escape from adaptive immunity is a hallmark for ATLL pathogenesis. However, the mechanisms by which ATLL cells evade NK-cell-mediated immunity have been poorly understood. Here we show that CD48 expression in ATLL cells determines the sensitivity for NK-cell-mediated cytotoxicity against ATLL cells. We performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening using two ATLL derived cell lines and discovered CD48 as one of the best enriched genes whose knockout conferred resistance to YT-1 NK cell line mediated cytotoxicity. The ability of CD48-knockout ATLL cells to evade NK cell effector function was confirmed using human primary NK cells with reduced IFNg induction and degranulation. We found that primary ATLL cells had reduced CD48 expression along with disease progression. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCL) also expressed lower levels of CD48 than normal T-cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK cell surveillance. Thus, this study demonstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK cell mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK cell-associated immunotherapies.
• The new generation tyrosine kinase inhibitor improves the survival of chronic myeloid leukemia patients after allogeneic stem cell transplantation.
  Yutaka Shimazu; Makoto Murata; Takeshi Kondo; Yosuke Minami; Takayoshi Tachibana; Noriko Doki; Naoyuki Uchida; Yukiyasu Ozawa; Shingo Yano; Takahiro Fukuda; Jun Kato; Takahide Ara; Testuya Eto; Jun Ishikawa; Hirohisa Nakamae; Junji Tanaka; Tatsuo Ichinohe; Yoshiko Atsuta; Tokiko Nagamura-Inoue
  Hematological oncology, 40, 3, 442, 456, Aug. 2022, [International Magazine]
  English, Scientific journal, The introduction of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) treatment has dramatically improved the prognosis of CML patients and reduced the number of patients receiving allogeneic stem cell transplantation (allo-SCT). However, the impact of the newest-generation TKIs on the overall survival (OS) after allo-SCT has not been well described. To investigate the beneficial effects of TKIs on the prognosis after allo-SCT, we conducted a retrospective observational study using the Transplant Registry Unified Management Program database in Japan. We analyzed 1188 patients (male/female: 738/450; median age: 44 years; range: 16-75) who underwent their first allo-SCT between January 2001 and December 2018. We divided the patients into two groups according to the TKI treatment used before allo-SCT: group 1 was treated with the first generation TKI imatinib; group 2 was treated with the second generation TKIs nilotinib, dasatinib, or bosutinib and/or the third generation TKI ponatinib. We compared the post allo-SCT OS between the two groups. The 3-year OS rates (95%CI) of groups 1 and 2 were 59.3% (54.8%-63.5%) and 65.8% (61.6%-69.6%), respectively (p = 0.017). Multivariate analysis confirmed that group 2 had superior OS after allo-SCT compared to group 1 (p = 0.002). Other factors associated with superior prognosis were age ≤65, performance status (PS) 0/1, a 6/6 HLA-matched donor and chronic-phase (CP) disease status at allo-SCT. A subgroup analysis showed poor prognoses for patients who could not obtain a molecular response before allo-SCT and patients with positive T315I mutation in the BCR/ABL gene. In group 2, early allo-SCT was correlated with superior OS in patients with a blast-crisis disease status at allo-SCT (p = 0.001). The cumulative incidence of non-relapse mortality rate significantly decreased in group 2 (p = 0.0005). The post allo-SCT OS was improved both by pre- and post-management of allo-SCT and by the introduction of newer TKIs.
• Adult patients with Ph+ ALL benefit from conditioning regimen of medium-dose VP16 plus CY/TBI.
  Mari Morita-Fujita; Yasuyuki Arai; Tadakazu Kondo; Kaito Harada; Naoyuki Uchida; Takashi Toya; Yukiyasu Ozawa; Takahiro Fukuda; Shuichi Ota; Makoto Onizuka; Yoshinobu Kanda; Yumiko Maruyama; Satoru Takada; Toshiro Kawakita; Takahide Ara; Tatsuo Ichinohe; Takafumi Kimura; Yoshiko Atsuta; Shinichi Kako
  Hematological oncology, 05 Jul. 2022, [International Magazine]
  English, Scientific journal, The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL.
• Improvements in allogeneic hematopoietic cell transplantation outcomes for adults with ALL over the past 3 decades.
  Satoshi Nishiwaki; Yu Akahoshi; Mari Morita-Fujita; Hiroaki Shimizu; Naoyuki Uchida; Yukiyasu Ozawa; Takahiro Fukuda; Masatsugu Tanaka; Kazuhiro Ikegame; Shuichi Ota; Yuta Katayama; Satoshi Takahashi; Toshiro Kawakita; Takahide Ara; Makoto Onizuka; Takafumi Kimura; Junji Tanaka; Yoshiko Atsuta; Yasuyuki Arai
  Blood advances, 6, 15, 4558, 4569, 23 Jun. 2022, [International Magazine]
  English, Scientific journal, Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising treatment for adult acute lymphoblastic leukemia (ALL), an intractable hematological malignancy. The trends in allo-HCT outcomes over the past 30 years were examined to verify the efficacy of evolving treatment methods and to identify further challenges. We analyzed data from a registry database that included 8467 adult ALL patients who underwent their first allo-HCT between 1990 and 2019. The period was divided into three 10-year intervals for analysis. Five-year overall survival improved from 48.2% to 70.2% in the first complete remission (CR1), from 25.6% to 44.1% in subsequent CR, and from 10.0% to 22.7% in non-CR. Non-relapse mortality improved over the 3 decades in each disease stage. However, the relapse rate only improved in CR1 every decade (26.3% to 15.9% in CR1, 33.4% to 32.8% in subsequent CR, and 53.6% to 54.8% in non-CR). Although there was continual improvements in adjusted survival for Philadelphia-chromosome (Ph) positive patients, the improvement was inadequate for Ph negative patients with t(4;11), t(8;14), t(14;18), or hypodiploidy. Allo-HCT outcomes for adults with ALL have improved over the past 30 years. Improved outcomes in the future will require more effective prevention of relapse in patients with ALL not in CR1 and in those with high-risk chromosomal abnormalities.
• Ideal body weight is useful for predicting neutrophil engraftment and platelet recovery for overweight and obese recipients in single-unit cord blood transplantation.
  Yosuke Okada; Hideki Nakasone; Takaaki Konuma; Naoyuki Uchida; Masatsugu Tanaka; Yasuhiro Sugio; Nobuyuki Aotsuka; Akihiko Nishijima; Yuna Katsuoka; Takahide Ara; Shuichi Ota; Makoto Onizuka; Masashi Sawa; Takafumi Kimura; Takahiro Fukuda; Yoshiko Atsuta; Junya Kanda; Fumihiko Kimura
  Transplantation and cellular therapy, 28, 8, 504.e1-504.e7, 13 May 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: Since cord blood (CB) units are usually selected based on the cell dose /kg, overweight (25 kg/m2 ≤ body mass index (BMI) < 30 kg/m2) and obese (30 kg/m2 ≤ BMI) recipients tend to have difficulty in getting appropriate CB units. In general, actual body weight (ABW) is used for CB unit selection. However, ideal body weight (IBW) has been reported to be more closely correlated with successful engraftment after autologous, allogeneic bone marrow, and peripheral blood stem cell transplantation than ABW. OBJECTIVES: We conducted this analysis to clarify the threshold of CD34+ cell doses based on ideal body weight (CD34IBW) and to compare the outcomes among the groups stratified by the threshold according to actual body weight (CD34ABW) and CD34IBW for overweight and obese recipients in cord blood transplantation (CBT). STUDY DESIGN: We retrospectively analyzed 650 overweight and obese recipients who received single-unit CBT. To focus on the recipients who received a low CD34+ cell dose /kg, those who received 1.5×105 CD34+ cells /ABW or more were excluded. Using a cut-off of 0.8×105 CD34+ cells/kg, we compared the outcomes in 3 groups with low CD34ABW and low CD34IBW (CD34Low/Low), low CD34ABW but high CD34IBW (CD34Low/High), and high CD34ABW and high CD34IBW (CD34High/High). RESULTS: Hematopoietic recoveries were significantly delayed in the CD34Low/Low group compared with those in the CD34Low/High group (hazard ratio (HR) 0.67 for neutrophil, P < 0.001; HR 0.72 for platelet, P = 0.014), while those were comparable in the CD34Low/High and CD34High/High groups (HR 1.22 for neutrophil, P = 0.16; HR 1.29 for platelet, P = 0.088). Moreover, the CD34Low/High group demonstrated longer overall survival than the CD34Low/Low group (HR 1.48, P = 0.011) and comparable survival to the CD34High/High group (HR 0.93, P = 0.68). CONCLUSIONS: This finding may address the lack of availability of CB units for some overweight and obese recipients for whom suitable donors are unavailable. Further investigations are warranted to evaluate the appropriateness of ABW and IBW.
• 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, May 2022, [International Magazine]
  English, Scientific journal, 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.
• Risk and Predictive Factors for Candidemia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group.
  Shun-Ichi Kimura; Kazuaki Kameda; Kaito Harada; Masuho Saburi; Keiji Okinaka; Akihito Shinohara; Naoyuki Uchida; Akihiko Nishijima; Yukiyasu Ozawa; Masatsugu Tanaka; Takuro Kuriyama; Yuta Katayama; Masashi Sawa; Kazuhiro Ikegame; Toshiro Kawakita; Yoshinobu Kanda; Hirohisa Nakamae; Takahide Ara; Takafumi Kimura; Atsushi Sato; Takahiro Fukuda; Yoshiko Atsuta; Hideki Nakasone
  Transplantation and cellular therapy, 28, 4, 209.e1-209.e9, Apr. 2022, [International Magazine]
  English, Scientific journal, Although antifungal prophylaxis that covers Candida species is a standard of care in allogeneic hematopoietic cell transplantation (HCT), candidemia mainly caused by non-albicans Candida species still occurs and is associated with a high mortality rate. This study aimed to evaluate the risk factors for candidemia after allogeneic HCT. Particularly, we evaluated the impact of patient factors such as hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and performance status (PS) in addition to well-recognized risk factors including donor type, delayed engraftment, and graft-versus-host disease (GVHD). By using data from a Japanese transplant registry database, we analyzed 26,236 pediatric and adult patients with hematological malignancies who underwent their first allogeneic HCT. The posttransplant period was divided into early (days 0-40), late (days 41-100) and very late (days 101-365) phases. The 1-year cumulative incidence of candidemia was 1.8%. When we analyzed pretransplantation factors, age ≥40 years (hazard ratio [HR] 1.85), male (HR 1.34), HCT-CI (HCT-CI 1-2, HR 1.56; HCT-CI ≥ 3, HR 2.21), PS ≥ 2 (HR 2.01), high-risk disease (HR 1.78) and donor type including HLA-mismatched related donor (MMRD) (HR 1.96), HLA-mismatched unrelated donor (HR 2.05), and cord blood (CB) (HR 2.85) were significantly associated with an increased incidence of candidemia. Focusing on the early phase (days 0-40), HCT-CI, PS, high-risk disease and CB transplantation together with engraftment and severe acute GVHD significantly affected the development of candidemia. In the late phase (days 41-100), higher HCT-CI, male, and donor type including MMRD, and CB were associated with the occurrence of candidemia together with acute GVHD and disease relapse. In the very late phase (days 101-365), HCT-CI ≥ 3 and high-risk disease significantly affected the occurrence of candidemia together with acute and chronic GVHD, and disease relapse. In addition to well-recognized risk factors including donor type, engraftment and GVHD, patient factors such as HCT-CI and PS were associated with the development of candidemia, which suggests that severely ill patients with transplantation-associated complications are more likely to develop candidemia.
• Registry data analysis of hematopoietic stem cell transplantation on systemic chronic active Epstein–Barr virus infection patients in Japan
  Masahide Yamamoto; Maho Sato; Yasushi Onishi; Yoji Sasahara; Hideki Sano; Masayoshi Masuko; Hirohisa Nakamae; Ken‐ichi Matsuoka; Takahide Ara; Kana Washio; Makoto Onizuka; Kenichiro Watanabe; Yoshiyuki Takahashi; Tsuneaki Hirakawa; Miwako Nishio; Chizuko Sakashita; Tohru Kobayashi; Akihisa Sawada; Tatsuo Ichinohe; Takahiro Fukuda; Yoshiko Hashii; Yoshiko Atsuta; Ayako Arai
  American Journal of Hematology, Wiley, 30 Mar. 2022
  Scientific journal
• Deletion of Y chromosome before allogeneic hematopoietic stem cell transplantation in male recipients with female donors.
  Masaharu Tamaki; Kazuaki Kameda; Shun-Ichi Kimura; Naonori Harada; Naoyuki Uchida; Noriko Doki; Masatsugu Tanaka; Kazuhiro Ikegame; Masashi Sawa; Yuta Katayama; Shigesaburo Miyakoshi; Takahide Ara; Junya Kanda; Makoto Onizuka; Takahiro Fukuda; Yoshiko Atsuta; Yoshinobu Kanda; Kimikazu Yakushijin; Hideki Nakasone
  Blood advances, 6, 6, 1895, 1903, 22 Mar. 2022, [International Magazine]
  English, Scientific journal, The graft-versus-leukemia (GVL) effect is one of the curative mechanisms of allogeneic hematopoietic stem cell transplantation (allo-HCT). H-Y antigens, which are encoded by Y chromosome, are important targets of the GVL effect. Thus, deletion of the Y chromosome (del[Y]) might cause the GVL effect to deteriorate in a transplantation involving a female donor and male recipient, although the clinical significance of the del(Y) group remains to be elucidated. In this study, we evaluated adult male patients who underwent allo-HCT between 2010 and 2019 in Japan. There were 155 cases in the del(Y) group and 4149 cases without del(Y) who underwent female-to-male allo-HCT. Del(Y) was significantly associated with inferior overall survival (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.00-1.53; P = .049) and an increased risk of relapse (HR, 1.40; 95% CI, 1.08-1.80; P = .0098) in multivariate analyses. There was no significant difference in nonrelapse mortality between recipients with and without del(Y) (HR, 1.08; 95% CI, 0.769-1.51; P = .67). In contrast, del(Y) was not significantly associated with any clinical outcomes in the cohort of male-to-male allo-HCT. A higher incidence of relapse might have been caused by attenuation of the GVL effect resulting from a lack of H-Y antigens. Because a GVL effect resulting from sex mismatch may not be expected in men with del(Y) who undergo allo-HCT with a female donor, additional post-allo-HCT strategies might be required to prevent disease relapse.
• Antithymocyte Globulin Potentially Could Overcome an Adverse Effect of Acute Graft-versus-Host Disease in Matched-Related Peripheral Blood Stem Cell Transplantation.
  Kotaro Miyao; Yachiyo Kuwatsuka; Makoto Murata; Koji Nagafuji; Takanori Teshima; Yuki Takeuchi; Souichi Shiratori; Yuho Najima; Naoyuki Uchida; Masatsugu Tanaka; Masashi Sawa; Shuichi Ota; Takahiro Fukuda; Yukiyasu Ozawa; Shinichi Kako; Toshiro Kawakita; Takahide Ara; Junji Tanaka; Yoshinobu Kanda; Yoshiko Atsuta; Junya Kanda; Seitaro Terakura
  Transplantation and cellular therapy, 28, 3, 153.e1-153.e11, Mar. 2022, [International Magazine]
  English, Scientific journal, Previous Japanese studies have shown that bone marrow transplantation (BMT) is associated with better survival compared with peripheral blood stem cell transplantation (PBSCT) from a matched related donor (MRD). PBSCT recipients have shown higher incidences of severe graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) compared with BMT recipients. In recent years, the efficacy and safety of antithymocyte globulin (ATG) for PBSCT recipients has been evaluated worldwide. In the present study, we aimed to compare BMT and PBSCT recipients to identify current improvements and unmet needs among MRD PBSCT recipients. In addition, we evaluated the impact of ATG administration on the outcomes of PBSCT recipients. We retrospectively analyzed patients age ≥16 years with acute leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia who underwent their first BMT or PBSCT from an MRD between 2009 and 2018 in Japan. A total of 3599 transplantations were performed (BMT, n = 1218; PBSCT without ATG [PBSCT-ATG(-)], n = 2288; PBSCT with ATG [PBSCT-ATG(+)], n = 93). The PBSCT-ATG(-) group had a higher NRM (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.08 to 1.57; P = .005) and lower overall survival (OS) (HR, 1.16; 95% CI, 1.04 to 1.30; P = .011) compared with the BMT group. Furthermore, the PBSCT-ATG(-) group had higher incidences of grade III-IV, stage 2-4 gut, high-risk, and steroid-refractory acute GVHD compared with the BMT group. Acute GVHD had a negative impact on NRM and OS. The PBSCT-ATG(-) group also was associated with an elevated risk of chronic GVHD (HR, 1.89; 95% CI, 1.24 to 2.57; P < .001) and extensive chronic GVHD (HR, 1.44; 95% CI, 1.23 to 1.68; P < .001). The incidences of acute GVHD, chronic GVHD, and NRM and chronic GVHD-free relapse-free survival rates were comparable between the PBSCT-ATG(+) and BMT groups. The OS of patients with acute GVHD was similar in the 3 donor groups. Patients treated with reduced-intensity conditioning in the PBSCT-ATG(+) group had a higher relapse rate and lower OS rate compared with those in the BMT group. In this Japanese cohort, standard calcineurin inhibitor-based GVHD prophylaxis was not sufficient for recipients of MRD PBSCT because of the high incidence of severe acute GVHD. Prophylactic ATG was found to be a promising strategy against GVHD.
• Disease-specific impact of anti-thymocyte globulin in allogeneic hematopoietic cell transplantation: a nationwide retrospective study on behalf of the JSTCT, transplant complications working group.
  Shigeo Fuji; Tsuneaki Hirakawa; Kuniko Takano; Noriko Doki; Masashi Sawa; Yoshinobu Kanda; Naoyuki Uchida; Takahide Ara; Toshihiro Miyamoto; Tetsuya Eto; Ken-Ichi Matsuoka; Toshiro Kawakita; Yukiyasu Ozawa; Yuta Katayama; Makoto Onizuka; Takahiro Fukuda; Yoshiko Atsuta; Hideki Nakasone
  Bone marrow transplantation, 57, 3, 479, 486, Mar. 2022, [International Magazine]
  English, Scientific journal, The disease-specific impact of anti-thymocyte globulin (ATG) in allogeneic hematopoietic cell transplantation (allo-HCT) has not been determined. We retrospectively assessed the impact of ATG in allo-HCT using nationwide registry data from the Japan Society for Transplantation and Cellular Therapy. We included patients who received their first allo-HCT between 2007 and 2018 for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or malignant lymphoma (ML). In total, 8747 patients were included: 7635 patients did not receive ATG and 1112 patients received ATG as GVHD prophylaxis. The median follow-up period of surviving patients was 1457 days. There was no significant impact of pretransplant ATG on the OS or NRM rates in patients with ALL, AML, or ML. In patients with MDS, the probability of 3-year OS was 53.3% in the non-ATG group and 64.2% in the ATG group (P = 0.001). The cumulative incidence rates of relapse and NRM at 3 years were 14.2% and 30.3% (95% CI 27.2-33.3%), respectively, in the non-ATG group and 17.1% and 18.1% in the ATG group (P = 0.15 and P < 0.001). The same finding was observed in a propensity-score matched cohort. Our study suggests that the clinical benefit of ATG could vary among hematological diseases.
• 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, Feb. 2022
  Japanese
• Characterization of myeloid neoplasms following allogeneic hematopoietic cell transplantation.
  Masatomo Kuno; Satoshi Yamasaki; Nobuharu Fujii; Yasushi Ishida; Takahiro Fukuda; Keisuke Kataoka; Naoyuki Uchida; Yuta Katayama; Maho Sato; Daishi Onai; Toshihiro Miyamoto; Shuichi Ota; Satoshi Yoshioka; Takahide Ara; Akira Hangaishi; Yoshiko Hashii; Makoto Onizuka; Tatsuo Ichinohe; Yoshiko Atsuta; Yoshihiro Inamoto
  American journal of hematology, 97, 2, 185, 193, 01 Feb. 2022, [International Magazine]
  English, Scientific journal, We compared characteristics of myeloid neoplasms (MNs) following allogeneic hematopoietic cell transplantation (HCT) versus autologous HCT using a Japanese HCT registry database. Among 43 788 patients who underwent allogeneic (n = 18 874) or autologous HCT (n = 24 914) for non-myeloid malignancies or non-malignant diseases, 352 developed MNs. The cumulative incidence of MNs was lower after allogeneic HCT than after autologous HCT (0.3% vs. 1.8% at 10 years, respectively, p < .001). Compared with autologous HCT, MNs following allogeneic HCT developed in younger patients (median, 42 vs. 57 years old, respectively) and sooner after HCT (median, 16 vs. 33 months, respectively). Approximately half of MNs following allogeneic HCT were donor-derived and occurred later than recipient-derived MNs (median, 26 vs. 6 months, respectively, p = .003). In multivariate analysis, reduced-intensity conditioning and cord blood transplantation were associated with MN development after allogeneic HCT. Overall survival was similar in patients who developed MNs following allogeneic versus autologous HCT (18% vs. 22% at 5 years, respectively, p = .48). Patient age ≥ 55 years, the presence of previous HCT, AML subtype, and chromosome 5 or 7 abnormalities were adverse factors for overall survival after MN diagnosis. Further research is warranted to elucidate the mechanisms of MN development following allogeneic HCT.
• Impact of HLA Epitope Matching on Outcomes After Unrelated Bone Marrow Transplantation.
  Makoto Iwasaki; Junya Kanda; Hidenori Tanaka; Takero Shindo; Takahiko Sato; Noriko Doki; Takahiro Fukuda; Yukiyasu Ozawa; Tetsuya Eto; Naoyuki Uchida; Yuta Katayama; Keisuke Kataoka; Takahide Ara; Shuichi Ota; Makoto Onizuka; Yoshinobu Kanda; Tatsuo Ichinohe; Yoshiko Atsuta; Satoko Morishima
  Frontiers in immunology, 13, 811733, 811733, 2022, [International Magazine]
  English, Scientific journal, The significance of antibody-identified epitopes stimulating humoral alloimmunity is not well understood in the identification of non-permissive human leukocyte antigen (HLA) mismatching patterns in hematopoietic stem cell transplantation (HSCT). This was a retrospective study in a cohort of 9,991 patients who underwent their first HSCT for hematologic malignancies from unrelated bone marrow donors in the Transplant Registry Unified Management Program (TRUMP). HLA eplet mismatches (EMM) were quantified using HLAMatchmaker (HLAMM). The median age of patients was 48 years (range, 16 to 77). The number of EMM in recipient-donor pairs in our study population ranged from 0 to 37 in HLA class I (median, 0) and 0 to 60 in HLA class II (median, 1). In addition to the known high-risk mismatch patterns in the Japanese cohort, HLA-C EMM in the GVH direction was associated with a significantly higher risk for grade III-IV aGVHD, leading to a higher risk of non-relapse mortality and lower overall survival (compared with HLA-C matched patients, HR 1.67, 95% CI 1.44-1.95; HR 1.39, 95% CI 1.25-1.54; HR 1.20, 95% CI 1.10-1.30, respectively). HLAMM-based epitope matching might be useful for identifying patients who are at high risk for serious complications after HSCT from HLA mismatched unrelated donors.
• Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT.
  Takayuki Inoue; Motoko Koyama; Katsuji Kaida; Kazuhiro Ikegame; Kathleen S Ensbey; Luke Samson; Shuichiro Takahashi; Ping Zhang; Simone A Minnie; Satoshi Maruyama; Shinichi Ishii; Takashi Daimon; Takahiro Fukuda; Hirohisa Nakamae; Takahide Ara; Yumiko Maruyama; Ken Ishiyama; Tatsuo Ichinohe; Yoshiko Atsuta; Bruce R Blazar; Scott N Furlan; Hiroyasu Ogawa; Geoffrey R Hill
  JCI insight, 6, 22, 22 Nov. 2021, [International Magazine]
  English, Scientific journal, Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes, with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities, but it typically requires intensive immunosuppression with posttransplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here, we demonstrate in preclinical models that glucocorticoid administration from days -1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the BM, promoting donor T cell residency. This results in significant reductions in GVHD while promoting potent GVL effects; relapse in recipients receiving glucocorticoids, vehicle, or PT-Cy was 12%, 56%, and 100%, respectively. Intriguingly, patients with acute myeloid leukemia not in remission who received unmanipulated haplo-SCT and peritransplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%; 95% CI, 18%-47%) with high overall survival at 3 years (58%; 95% CI, 38%-74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.
• Novel Insights Into the Mechanism of GVHD-Induced Tissue Damage
  Takahide Ara; Daigo Hashimoto
  Frontiers in Immunology, 12, Frontiers Media SA, 27 Aug. 2021, [Lead author], [International Magazine]
  Scientific journal, 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.
• 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, May 2021, [International Magazine]
  English, Scientific journal, 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.
• Chronic Diarrhea as the Presenting Feature of Amyloidosis with Multiple Myeloma: A Case Report Diagnosed by a Myocardial Biopsy.
  Shinsuke Otagiri; Sae Nakajima; Takehiko Katsurada; Kensuke Sakurai; Kana Yamanashi; Takahide Ara; Emi Takakuwa; Tomoko Mitsuhashi; Naoya Sakamoto
  Internal medicine (Tokyo, Japan), 60, 8, 1197, 1203, 15 Apr. 2021, [Domestic magazines]
  English, Scientific journal, A 73-year-old woman with a history of diarrhea for one year and other various symptoms was admitted to our hospital. Gastrointestinal endoscopy that included enteroscopy with multiple biopsies was performed. However, no significant findings were observed. Electrocardiography showed low voltage in all limb leads, and an echocardiogram showed thickened cardiac walls with granular sparkling pattern. A myocardial biopsy revealed amyloidosis, and a bone marrow biopsy showed multiple myeloma. This case suggests that we should suspect the possibility of amyloidosis in a patient with diarrhea and various symptoms involving multiple organ systems. Additionally, electrocardiograms and echocardiograms should be performed even when gastrointestinal biopsies reveal negative results.
• Low-dose lenalidomide and dexamethasone therapy after melphalan-prednisolone induction in elderly patients with newly diagnosed multiple myeloma.
  Yasushi Onishi; Hisayuki Yokoyama; Yuna Katsuoka; Toshihiro Ito; Tomohumi Kimura; Joji Yamamoto; Shinji Nakajima; Osamu Sasaki; Takahide Ara; Koichiro Minauchi; Osamu Fukuhara; Naoki Kobayashi; Hideyoshi Noji; Shuichi Ota; Hideo Harigae
  Annals of hematology, 99, 10, 2351, 2356, Springer Science and Business Media {LLC}, Oct. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Lenalidomide (Len) and dexamethasone (dex) therapy is a standard therapy in patients with multiple myeloma. Elderly or unfit patients may reduce Len or dex doses to prevent toxicities that lead to treatment discontinuation. However, there have been few studies evaluating the efficacy and safety of lower doses of Len and dex. We conducted a phase II study of 1.5-year low-dose Len and dex therapy following melphalan and prednisolone (MP), the number of which cycles was determined by a response within 9 cycles. The Len dose was 10 mg daily and the dex dose was 20 mg weekly, which were continued for 1.5 years. Twenty-one patients were enrolled. The median number of cycles of MP was 3 (range, 2-9). The overall response rate was 81% and a very good partial response or better was achieved in 33.3% of patients. The median follow-up time for survivors was 70.5 months (range, 42-83 months), the median progression-free survival (PFS) was 27 months (95% CI, 21-33 months), and the median overall survival was not reached. Grade 3 or 4 adverse events were observed in 28.6% of patients. In conclusion, the low-dose Len and dex therapy safely achieved comparable efficacies to the standard-dose regimen in elderly patients with newly diagnosed multiple myeloma. UMIN000007889.
• 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, 01 Jul. 2020, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal, 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 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, Apr. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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, Mar. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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.
• AIDS患者に発症した肝EBV関連平滑筋腫の1例
  金谷 本真; 坂本 圭太; 加藤 扶美; 真鍋 徳子; 工藤 興亮; 笠原 耕平; 荒 隆英; 高桑 恵美; 桑原 健
  Japanese Journal of Radiology, 38, Suppl., 8, 8, (公社)日本医学放射線学会, Feb. 2020
  Japanese
• ART開始後に縮小傾向を認めたEBV-associated smooth muscle tumor合併AIDSの一例
  荒 隆英; 遠藤 知之; 後藤 秀樹; 笠原 耕平; 長谷川 裕太; 横山 翔大; 高桑 恵美; 松野 吉宏; 橋野 聡; 豊嶋 崇徳
  日本エイズ学会誌, 21, 4, 426, 426, (一社)日本エイズ学会, Nov. 2019
  Japanese
• 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, 09 Apr. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, 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.
• 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, Aug. 2018
  English, Scientific journal
• Intestinal Lymphatic Endothelial Cells Produce R-Spondin3.
  Reiki Ogasawara; Daigo Hashimoto; Shunsuke Kimura; Eiko Hayase; Takahide Ara; Shuichiro Takahashi; Hiroyuki Ohigashi; Kosuke Yoshioka; Takahiro Tateno; Emi Yokoyama; Ko Ebata; Takeshi Kondo; Junichi Sugita; Masahiro Onozawa; Toshihiko Iwanaga; Takanori Teshima
  Scientific reports, 8, 1, 10719, 10719, 16 Jul. 2018, [International Magazine]
  English, Scientific journal, 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.
• 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, 03 May 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Graft-versus-host disease (GVHD) is the major complication after allogeneic stem cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury of intestinal stem cells. However, it remains to be investigated whether skin stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs) contribute to folliculogenesis and have a multipotent capacity to regenerate all epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine models of SCT. We found that GVHD reduced Lgr5+ HFSCs in association with impaired hair regeneration and wound healing in the skin after SCT. Topical corticosteroids, a standard of care for a wide range of skin disorders including GVHD, damaged HFSCs and failed to improve skin homeostasis, despite of their anti-inflammatory effects. In contrast, JAK1/2 inhibitor ruxolitinib significantly ameliorated skin GVHD, protected Lgr5+ HFSCs, and restored hair regeneration and wound healing after SCT. We, for the first time, found that GVHD targets Lgr5+ HFSCs and that topical ruxolitinib represents a novel strategy to protect skin stem cells and maintain skin homeostasis in GVHD.
• 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
  The Journal of experimental medicine, 214, 12, 3507, 3518, 04 Dec. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal, The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant α-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host-microbiota cross talk toward therapeutic benefits.
• [Serum ALP elevation early after treatment is a predictor for response in myeloma patients treated with bortezomib].
  Koichiro Minauchi; Kanako Shima; Junichi Hashiguchi; Takahide Ara; Atsushi Yasumoto; Kenji Fujino; Masanobu Nakata; Masato Obara; Shuichi Ota; Kiyotoshi Imai; Teiichi Hirano; Yoshio Kiyama; Masahiro Ogasawara; Naoki Kobayashi; Masahiro Imamura
  [Rinsho ketsueki] The Japanese journal of clinical hematology, 56, 8, 1064, 8, Aug. 2015, [Domestic magazines]
  Japanese, Scientific journal, Several studies have shown the predictive value of elevated serum alkaline phosphatase (ALP) level in multiple myeloma (MM) patients treated with bortezomib (BTZ). We assessed the relationship between changes in ALP levels during treatment and response. Thirty patients treated with BTZ in our hospital were analyzed retrospectively. Of the patients analyzed, 12 were male, median age was 62 years (42-86), and 11 had a history of prior chemotherapy. Eighteen patients were treated with BTZ alone or in combination with dexamethasone, while the others were treated with a combination regimen employing an alkylating agent. Seven patients had undergone autologous stem cell transplantation following BTZ therapy. Ten of 28 patients showed ALP elevation of 25% or more from the baseline at 3 weeks, and 14 of the 28 had this finding at 6 weeks. Four of 5 patients who had achieved VGPR or more showed ALP elevation of 25% or more at 3 weeks, and all five had this finding by 6 weeks. No patient without ALP elevation achieved VGPR or a better response. ALP elevation exceeding 25% from the baseline by day 42 is significantly associated with a treatment response better than VGPR (p=0.019). In conclusion, ALP elevation during BTZ treatment is a valuable prognostic marker.
• Aclarubicin, Low-Dose Cytarabine Combined With G-CSF (CAG) Regimen For Patients Previously Treated Or Ineligible For Intensive Chemotherapy With Acute Myeloid Leukemia and Myelodysplastic Syndrom: A Single Center Experience
  Koichiro Minauchi; Masato Obara; Takahide Ara; Kanako Shima; Atsushi Yasumoto; Masanobu Nakata; Shuichi Ota; Kiyotoshi Imai; Teiichi Hirano; Yoshio Kiyama; Masahiro Ogasawara; Naoki Kobayashi; Masahiro Imamura
  BLOOD, 122, 21, Nov. 2013
  English

• CAR-T細胞製造時のferroptosis阻害はFoxo1の核内局在を維持し,CAR-T細胞の幹細胞性,持続性と有効性を強化する
  原田晋平; 橋本大吾; 塚本しほり; 一木朝絵; 齋藤祐美花; 宮島徹; LI Wenyu; 千丈創; ZHANG Zixuan; 菊池遼; 千葉雅尋; 大東寛幸; 荒隆英; 中川雅夫; 豊嶋崇徳, 日本輸血細胞治療学会誌, 71, 2, 2025
• 大量失血を伴う手術時におけるレナカパビルの血中濃度の推移
  遠藤知之; 田澤佑基; 遠藤知之; 田澤佑基; 新井崇之; 後藤秀樹; 松川敏大; 荒隆英; 長谷川祐太; 長井惇; 森木朝子; 高橋知希; 後藤了一; 後藤秀樹; 松川敏大; 荒隆英; 長谷川祐太; 長井惇; 森木朝子; 高橋知希; 後藤了一; 嶋村剛; 原貴信; 曽山明彦; 江口晋; 豊嶋崇徳; 江口晋; 豊嶋崇徳, 日本エイズ学会誌, 27, 4, 2025
• The Frequency of Blip and the Maintenance Rate of Target Not Detected (TND) in HIV-Positive Individuals Treated with a Two-Drug Regimen
  遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 松川敏大; 松川敏大; 荒隆英; 荒隆英; 長谷川祐太; 長谷川祐太; 須藤啓斗; 須藤啓斗; 宮島徹; 宮島徹; 長井惇; 長井惇; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 27, 2, 2025
• GVHDによる腸幹細胞の炎症記憶は腸上皮の抗原提示とアポトーシスを促進する
  宮島徹; 橋本大吾; 森木朝子; 小島圭祐; 塚本しほり; 一木朝絵; 齋藤祐美花; 李文ぎょく; 張紫せん; 原田晋平; 千丈創; 横井友樹; 長谷川祐太; 大東寛幸; 荒隆英; 中村公則; 谷口浩二; 豊嶋崇徳, 日本血液疾患免疫療法学会学術集会プログラム・抄録集, 17th, 2025
• Multiplex PCR on Cerebrospinal Fluid to Diagnose Central Nervous System Complications in AIDS Patients
  松川敏大; 松川敏大; 遠藤知之; 遠藤知之; 遠藤知之; 森木朝子; 森木朝子; 長井惇; 長井惇; 宮島徹; 宮島徹; 長谷川祐太; 長谷川祐太; 荒隆英; 荒隆英; 後藤秀樹; 後藤秀樹; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 27, 3, 2025
• Zanubrutinibが奏効したBing-Neel症候群の1例
  野島慎悟; 野津麟太郎; 堀北風花; 宮島徹; 吉田匠汰; 木村弘幸; 荒隆英; 小笠原励起; 松川敏大; 白鳥聡一; 中川雅夫; 豊嶋崇徳, 臨床血液, 66, 11, 2025
• Selection of High Survival Benefit Cases by Letermovir: Linear Regression vs. Machine Learning Model
  赤星佑; 赤星佑; 仲宗根秀樹; 竹中克斗; 荒隆英; 多田雄真; 土岐典子; 内田直之; 田中正嗣; 長谷川祐太; 武田航; 西田徹也; 石川淳; 栗田尚樹; 澤正史; 鬼塚真仁; 賀古真一; 藤原慎一郎; 片岡圭亮; 片岡圭亮; 河村浩二; 福田隆浩; 神田善伸; 神田善伸; 熱田由子; 熱田由子; 藥師神公和, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 47th, 2025
• 低用量ST合剤による同種造血幹細胞移植後ニューモシスチス肺炎の予防効果についての検討
  荒隆英; 遠藤知之; 長谷川祐太; 大東寛幸; 白鳥聡一; 橋本大吾; 豊嶋崇徳, 日本内科学会雑誌, 113, 2024
• Impact of duration of response of prior therapy on therapeutic efficacy of CAR-T therapy in DLBCL
  後藤秀樹; 荒隆英; 大東寛幸; 長谷川祐太; 千葉雅尋; 千丈創; 松川敏大; 安本篤史; 白鳥聡一; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 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, 46th, 2024
• Low-molecular-weight heparin and the incidence of SOS/VOD during HSCT
  白鳥聡一; 長谷川祐太; 大東寛幸; 荒隆英; 松川敏大; 安本篤史; 後藤秀樹; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 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, 46th, 2024
• 骨髄異形成症候群に対するHLA半合致末梢血幹細胞移植とHLA適合非血縁者間移植の比較
  中舎 洋輔; 康 秀男; 小沼 貴晶; 下村 良充; 石山 謙; 糸永 英弘; 日野 雅之; 土岐 典子; 西田 徹也; 荒 隆英; 松岡 賢市; 神田 善伸; 福田 隆浩; 熱田 由子; 中前 博久, 日本血液学会学術集会, 85回, 168, 168, Oct. 2023
  (一社)日本血液学会, English
• 中枢病変を有した成人T細胞性白血病/リンパ腫(ATLL)の1例
  塚本しほり; 清水亜衣; 森祐斗; 横山翔大; 荒隆英; 松川敏大; 白鳥聡一; 中川雅夫; 遠藤知之; 高桑恵美; 加留部謙之輔; 松野吉宏; 豊嶋崇徳, 臨床血液, 64, 7, 2023
• The incidence of Pneumocystis pneumonia after allogeneic hematopoietic stem cell transplantation
  荒隆英; 長谷川祐太; 大東寛幸; 安本篤史; 白鳥聡一; 後藤秀樹; 杉田純一; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 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
• Retrospective analysis of allo-SCT for adult T cell leukemia/lymphoma in single institution
  荒隆英; 横山翔大; 長谷川祐太; 大東寛幸; 松川敏大; 安本篤史; 白鳥聡一; 後藤秀樹; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 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, 45th, 2022
• Bacillus species bacteremia in patients who underwent hematopoietic stem cell transplant
  森祐斗; 荒隆英; 横山翔大; 松川敏大; 白鳥聡一; 中川雅夫; 遠藤知之; 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, 45th, 2022
• CRP is a predictive marker of the antifebrile effect of tocilizumab on CRS during CAR-T cell therapy
  横山翔大; 後藤秀樹; 荒隆英; 森祐斗; 長谷川祐太; 大東寛幸; 松川敏大; 安本篤史; 白鳥聡一; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 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, 45th, 2022
• Association between candidemia and non-infectious interstitial pneumonia after allogeneic HCT
  木村俊一; 赤星佑; 赤星佑; 白鳥聡一; 冲中敬二; 冲中敬二; 原田介斗; 内田直之; 土岐典子; 池亀和博; 中前博久; 田中正嗣; 高田覚; 河北敏郎; 松岡賢市; 荒隆英; 太田秀一; 澤正史; 鬼塚真仁; 福田隆浩; 熱田由子; 熱田由子; 神田善伸; 神田善伸; 仲宗根秀樹, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 45th, 2022
• VGCV中止による免疫回復にて改善を認めたCMV感染症合併のAIDS症例
  横山翔大; 横山翔大; 遠藤知之; 遠藤知之; 宮島徹; 宮島徹; 須藤啓斗; 須藤啓斗; 高橋承吾; 高橋承吾; 長谷川祐太; 長谷川祐太; 荒隆英; 荒隆英; 松川敏大; 松川敏大; 後藤秀樹; 後藤秀樹; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 24, 4, 2022
• 当院における「いきなりエイズ」症例の患者特性の検討
  荒隆英; 荒隆英; 遠藤知之; 遠藤知之; 宮島徹; 宮島徹; 須藤啓斗; 須藤啓斗; 高橋承吾; 高橋承吾; 横山翔大; 横山翔大; 長谷川祐太; 長谷川祐太; 松川敏大; 松川敏大; 後藤秀樹; 後藤秀樹; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 24, 4, 2022
• 薬害HIV感染症患者における冠動脈スクリーニング
  遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 松川敏大; 松川敏大; 荒隆英; 荒隆英; 長谷川祐太; 長谷川祐太; 横山翔大; 横山翔大; 高橋承吾; 高橋承吾; 須藤啓斗; 須藤啓斗; 宮島徹; 宮島徹; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 24, 4, 2022
• HIV感染者に対する骨代謝異常の後方視的解析
  松川敏大; 松川敏大; 遠藤知之; 遠藤知之; 宮島徹; 宮島徹; 須藤啓斗; 須藤啓斗; 高橋承吾; 高橋承吾; 横山翔大; 横山翔大; 長谷川祐太; 長谷川祐太; 荒隆英; 荒隆英; 後藤秀樹; 後藤秀樹; 橋野聡; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 24, 4, 2022
• Letermovir Is Effective for Prevention of Cytomegalovirus Reactivation in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide
  Takahide Ara; Yuta Hasegawa; Hiroyuki Ohigashi; Souichi Shiratori; Atsushi Yasumoto; Hideki Goto; Junichi Sugita; Masahiro Onozawa; Masao Nakagawa; Kaoru Kahata; Daigo Hashimoto; Takanori Teshima, BLOOD, 138, Nov. 2021
  English, Summary international conference
• Safety and efficacy of Defibrotide for sinusoidal obstruction syndrome
  木村弘幸; 白鳥聡一; 大東寛幸; 荒隆英; 安本篤史; 後藤秀樹; 中川雅夫; 杉田純一; 小野澤真弘; 加畑馨; 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
• Recent Advances In Allogeneic Hematopoietic Stem Cell Transplantation.
  荒隆英; 豊嶋崇徳, Journal of Clinical Rehabilitation, 30, 7, 2021
• Multiplex PCR法を用いたAIDS患者における髄液病原体の網羅的解析
  遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 荒隆英; 荒隆英; 長谷川祐太; 横山翔大; 横山翔大; 高橋承吾; 高橋承吾; 米田和樹; 米田和樹; 小野澤真弘; 中川雅夫; 橋本大吾; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 23, 4, 2021
• 急性前立腺炎後に発症したFitz-HughCurtis症候群のMSMの一例
  宮島徹; 大東寛幸; 横山慶人; 岡田怜; 長谷川祐太; 荒隆英; 荒隆英; 後藤秀樹; 後藤秀樹; 杉田純一; 小野澤真弘; 遠藤知之; 遠藤知之; 橋本大吾; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 23, 4, 2021
• Loeffler心内膜炎による左室内血栓および壁運動異常を併発したPDGFRA遺伝子再構成を伴う慢性好酸球性白血病の1例
  吉田匠汰; 荒隆英; 塚本しほり; 齋藤祐美花; 伊藤謙一; 白鳥聡一; 後藤秀樹; 中川雅夫; 遠藤知之; 豊嶋崇徳, 臨床血液, 62, 12, 2021
• Fluid retention after allogeneic hematopoietic stem cell transplantation has a poor prognosis
  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
• 少量ATGを用いたPBSCTの移植成績-R-PBSCTとUR-PBSCTの比較検討-
  白鳥聡一; 大東寛幸; 高橋秀一郎; 荒隆英; 横山絵美; 後藤秀樹; 杉田純一; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 橋本大吾; 豊嶋崇徳, 日本輸血細胞治療学会誌, 66, 2, 2020
• Intestinal microbiota plays a critical role in reactive granulopoiesis in response to neutropenia
  陳げん仲; 橋本大吾; 江端浩; 高橋秀一郎; 早瀬英子; 横山絵美; 荒隆英; 大東寛幸; 長谷川裕太; 菊池遼; 張紫せん; 豊嶋崇徳, 腸内細菌学雑誌, 34, 2, 2020
• The generation-based analysis of the outcome of allo SCT Hokkaido Leukemia Network AML cohort study
  米田和樹; 小野澤真弘; 日高大輔; 横山翔大; 宮下直洋; 荒隆英; 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; 宮城島拓人; 柿木康孝; 黒澤光俊; 小林一; 岩崎博; 豊嶋崇徳, 日本造血細胞移植学会総会プログラム・抄録集, 42nd, 2020
• Efficacy of low-dose and short term cidofovir treatment for adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients
  大東寛幸; 後藤秀樹; 藤本勝也; 荒隆英; 白鳥聡一; 杉田純一; 小野澤真弘; 森康雄; 吉本五一; 橋本大吾; 遠藤知之; 加藤光次; 豊嶋崇徳, 日本造血細胞移植学会総会プログラム・抄録集, 42nd, 2020
• Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic graft-versus-host disease
  大東寛幸; 橋本大吾; 高橋秀一郎; 荒隆英; 山川知宏; 早瀬英子; 杉田純一; 小野澤真弘; 中川雅夫; 豊嶋崇徳, 日本造血細胞移植学会総会プログラム・抄録集, 42nd, 2020
• Intestinal goblet cells play a protective role against GVHD via Lypd8 dependent manner after allogeneic hematopoietic stem cell transplantation
  荒隆英; 橋本大吾; 早瀬英子; NOIZAT Clara; 菊池遼; 長谷川祐太; 奥村龍; 竹田潔; 豊嶋崇徳, 腸内細菌学雑誌, 34, 2, 2020
• HIV感染血友病患者の認知機能及び心理社会的問題の現状把握に関する研究
  石田陽子; 石田陽子; 遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 荒隆英; 荒隆英; 長谷川祐太; 長谷川祐太; 横山翔大; 横山翔大; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 22, 4, 2020
• HIV関連悪性リンパ腫の臨床的特徴の検討
  遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 荒隆英; 荒隆英; 長谷川祐太; 長谷川祐太; 横山翔大; 横山翔大; 橋本大吾; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 22, 4, 2020
• 同種造血幹細胞移植後早期のプロカルシトニン測定の有用性についての検討
  大東寛幸; 杉田純一; 荒隆英; 白鳥聡一; 後藤秀樹; 小野澤真弘; 中川雅夫; 橋本大吾; 遠藤知之; 豊嶋崇徳, 日本血液学会学術集会抄録(Web), 82nd, 2020
• 再発難治性DLBCLへのtisagenlecleucelの安全性
  後藤秀樹; 杉田純一; 杉田純一; 大東寛幸; 荒隆英; 高橋秀一郎; 高橋秀一郎; 横山絵美; 白鳥聡一; 小野澤真弘; 中川雅夫; 加畑馨; 加畑馨; 遠藤知之; 橋本大吾; 豊嶋崇徳; 豊嶋崇徳, 日本血液学会学術集会抄録(Web), 82nd, 2020
• 同種造血幹細胞移植後肺合併症の診断における気管支肺胞洗浄液CD4+/CD8+比の有用性
  千丈創; 杉田純一; 岡田耕平; 鈴木雅; 千葉雅尋; 大東寛幸; 高橋秀一郎; 荒隆英; 横山絵美; 白鳥聡一; 後藤秀樹; 小野澤真弘; 中川雅夫; 加畑馨; 遠藤知之; 橋本大吾; 豊嶋崇徳, 日本血液学会学術集会抄録(Web), 82nd, 2020
• 各種移植片対宿主病予防法におけるレテルモビル予防内服時の至適タクロリムス初回投与量に関する検討
  荒隆英; 大東寛幸; 高橋秀一郎; 白鳥聡一; 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, 日本血液学会学術集会抄録(Web), 82nd, 2020
• 妊娠後期に診断された発作性夜間ヘモグロビン尿症に対してeculizumabを導入した1例
  小島 圭祐; 荒 隆英; 遠藤 知之; 高橋 承吾; 米田 和樹; 横山 翔大; 笠原 耕平; 白鳥 聡一; 後藤 秀樹; 中川 雅夫; 森川 守; 山本 準也; 豊嶋 崇徳, 臨床血液, 60, 11, 1583, 1583, Nov. 2019
  (一社)日本血液学会-東京事務局, Japanese
• ART時代におけるHIV感染者の死因の検討
  荒隆英; 遠藤知之; 後藤秀樹; 日高大輔; 吉岡康介; 宮下直洋; 笠原耕平; 橋野聡; 豊嶋崇徳, 日本内科学会雑誌, 108, 2019
• 10年という長期寛解後に全身再発を来した節外性NK/T cell lymphoma(鼻型)の1例
  土田直央; 荒隆英; 遠藤知之; 横山翔大; 笠原耕平; 白鳥聡一; 後藤秀樹; 中川雅夫; 豊嶋崇徳; 福井秀章; 松野吉宏, 臨床血液, 60, 7, 2019
• 当院における60歳以上の高齢者に対する同種造血幹細胞移植の後方視的解析
  横山翔大; 白鳥聡一; 荒隆英; 笠原耕平; 高橋秀一郎; 宮下直洋; 後藤秀樹; 小野澤真弘; 中川雅夫; 加畑馨; 杉田純一; 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, 41st, 2019
• HIV感染症合併血友病患者における微小脳出血の経時的評価
  遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 荒隆英; 荒隆英; 長谷川祐太; 長谷川祐太; 横山翔大; 横浜翔大; 中川雅夫; 加畑馨; 橋本大吾; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 21, 4, 2019
• 高感度CRPによるHIV感染者の慢性炎症の評価
  遠藤知之; 遠藤知之; 後藤秀樹; 後藤秀樹; 荒隆英; 荒隆英; 吉岡康介; 吉岡康介; 宮下直洋; 笠原耕平; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 20, 4, 2018
• Establishment of the Hokkaido HIV Dialysis Network and the Assessment of Its Efficacy
  遠藤 知之; センテノ田村 恵子; 渡部 恵子; 後藤 秀樹; 宮下 直洋; 荒 隆英; 笠原 耕平; 橋野 聡; 豊嶋 崇徳, 日本エイズ学会誌 = The journal of AIDS research, 20, 3, 199, 205, 2018
  日本エイズ学会, Japanese
• 北海道HIV透析ネットワークの構築とその有効性の検討
  遠藤知之; 遠藤知之; センテノ(田村)恵子; センテノ(田村)恵子; 渡部恵子; 渡部恵子; 宮下直洋; 宮下直洋; 荒隆英; 荒隆英; 後藤秀樹; 後藤秀樹; 橋野聡; 橋野聡; 豊嶋崇徳; 豊嶋崇徳, 日本エイズ学会誌, 19, 4, 2017
• Bortezomib療法を安全に施行し得た肺がん合併多発性骨髄腫
  小原 雅人; 中田 匡信; 木山 善雄; 藤野 賢治; 伊藤 洋輔; 西海 豊寛; 橋口 淳一; 荒 隆英; 安本 篤史; 皆内 康一郎; 太田 秀一; 今井 陽俊; 平野 貞一; 小笠原 正浩; 小林 直樹; 今村 雅寛, 臨床血液, 56, 6, 723, 723, Jun. 2015
  (一社)日本血液学会-東京事務局, Japanese
• ALLに対する同種造血幹細胞移植後早期に発症した治療関連AMLの2例
  橋口 淳一; 皆内 康一郎; 平野 貞一; 荒 隆英; 藤野 賢治; 安本 篤史; 小原 雅人; 中田 匡信; 太田 秀一; 今井 陽俊; 小笠原 正浩; 木山 善雄; 小林 直樹; 今村 雅寛, 臨床血液, 56, 1, 59, 59, Jan. 2015
  (一社)日本血液学会-東京事務局, Japanese
• 骨髄異形成症候群に対する同種造血幹細胞移植の後方視的解析
  安本 篤史; 橋口 淳一; 荒 隆英; 藤野 賢治; 皆内 康一郎; 小原 雅人; 太田 秀一; 中田 匡信; 今井 陽俊; 平野 貞一; 小笠原 正浩; 木山 善雄; 小林 直樹; 今村 雅寛, 臨床血液, 56, 1, 63, 63, Jan. 2015
  (一社)日本血液学会-東京事務局, Japanese
• 正常核型を示しPCRと形態から急性前骨髄性白血病(APL)と診断した1例
  荒 隆英; 太田 秀一; 安本 篤史; 皆内 康一郎; 小原 雅人; 中田 匡信; 平野 貞一; 今井 陽俊; 小笠原 正浩; 木山 善雄; 小林 直樹; 今村 雅寛, 臨床血液, 55, 7, 847, 847, Jul. 2014
  (一社)日本血液学会-東京事務局, Japanese

• 肝臓GVHDにおける腸内細菌叢と肝臓免疫担当細胞とのクロストークの解明
  科学研究費助成事業
  01 Apr. 2021 - 31 Mar. 2025
  荒 隆英
  まず肝臓GVHDのマウスモデルの作製を行った。すでに急性GVHDのマウスモデルとして確立している、ドナーにB6マウス(H-2b)、レシピエントにBDF1マウス(H-2b/d)を用いたMHC半合致骨髄移植モデルを用いた。ただし、このモデルでは肝臓GVHDに比して腸管GVHDが先行するため、前処置として用いる全身放射線照射の照射量を軽減させることで腸管GVHDによる死亡を軽減させて、肝臓GVHDの評価を行えるように調整した。
  続いて、このモデルを用いて肝臓GVHDの有無について組織学的検討を行った。allogeneic群ではsyngeneic群と比較して、移植後14日目以降の肝臓において、炎症細胞の門脈域への浸潤、胆管上皮細胞のアポトーシス・剥離などの所見が有意に認められた。これらの組織学的所見はヒトにおける肝臓GVHDの組織所見と類似しており、本移植モデルが肝臓GVHDの評価に有用と考えられた。
  さらに、移植後に肝臓へ浸潤する単核細胞(liver-infiltrating mononuclear cells: LMCs)の動態についてフローサイトメトリー解析を行った。移植後1週間でLMCsは全てドナー由来の細胞に置き換わっていた。また、allogeneic群ではsyngeneic群と比較して有意に細胞浸潤を認めたが、CD4陽性/CD8陽性T細胞が移植後1週間肝臓へ浸潤するのに対して、単球/マクロファージはT細胞に遅れて移植後2～3週後に浸潤してくることが明らかとなり、両者の間になんらかのクロストークが存在する可能性が示唆された。
  日本学術振興会, 若手研究, 北海道大学, 21K16259