2023年07月, 国立研究開発法人科学技術振興機構, 第48回（令和5年度）井上春成賞　　　　　　　　　　　　　　　
新型コロナウイルス抗原定量試薬による唾液検査の開発と空港検疫への応用

2023年02月, 北海道総合政策部次世代社会戦略局科学技術振興課, 令和4年度北海道科学技術賞　　　　　　　　　　　　　　　
新型コロナウイルス感染症の唾液診断法の開発

2022年12月, 第一生命保険株式会社, 第74回 保健文化賞　　　　　　　　　　　　　　　

2022年10月, 一般社団法人 日本血液学会, 第11回 日本血液学会学会賞　　　　　　　　　　　　　　　

2021年10月, 北海道新聞社, 北海道新聞文化賞（学術部門）　　　　　　　　　　　　　　　

2021年06月, 一般社団法人 減災サステナブル技術協会, 防災・減災×サステナブル大賞 サステナブル部門 グローバル賞　　　　　　　　　　　　　　　
唾液採取による新型コロナＰＣＲ検査

2021年02月, 国立大学法人北海道大学, 令和２年度北海道大学教育研究総長表彰　　　　　　　　　　　　　　　

2020年10月, 公益財団法人伊藤医薬学術交流財団, 令和2年度 伊藤太郎特別賞　　　　　　　　　　　　　　　

2019年03月, 一般社団法人日本造血細胞移植学会, 第1回日本造血細胞移植学会学会賞　　　　　　　　　　　　　　　
豊嶋 崇徳

2016年, 北海道大学大学院医学研究科・医学部医学科, 平成27年度北海道大学大学院医学研究科・医学部医学科 優秀研究賞　　　　　　　　　　　　　　　
豊嶋 崇徳

2012年10月, International Journal of Hematology 編集長賞　　　　　　　　　　　　　　　
豊嶋 崇徳

2005年, 武田科学振興財団, 一般研究奨励賞　　　　　　　　　　　　　　　
豊嶋 崇徳

1999年, Travel Award, 1999 Annual Meeting of American Society of Hematology　　　　　　　　　　　　　　　
豊嶋 崇徳

1999年, Best Abstract Award, 1999 American Society of Blood and Marrow Transplantation　　　　　　　　　　　　　　　

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

Vedolizumab for prevention of lower-GI acute GVHD in the Japanese subgroup analysis of the phase 3 GRAPHITE study.
Tatsunori Goto, Hiroshi Okamura, Takashi Ikeda, Yasuo Mori, Souichi Shiratori, Shin-Ichiro Fujiwara, Noriko Doki, Ken-Ichi Matsuoka, Yuta Katayama, Yi-Bin Chen, Yngvar Fløisand, Guillermo Rossiter, Johan Jansson, Ryou Nakaya, Takanori Teshima
International journal of hematology, 2025年03月12日, ［国内誌］
英語, 研究論文（学術雑誌）, In the randomized, double-blind, phase 3 GRAPHITE study (NCT03657160), anti-α4β7 integrin antibody vedolizumab showed greater efficacy than placebo for prevention of lower-gastrointestinal (GI) acute graft-versus-host disease (aGVHD) after unrelated allogenic hematopoietic stem cell transplantation (allo-HSCT). This post hoc analysis assessed the efficacy and safety of vedolizumab versus placebo for lower-GI aGVHD prevention in Japanese and non-Japanese patients, when added to standard GVHD prophylaxis (calcineurin inhibitor + methotrexate/mycophenolate mofetil + / - anti-thymocyte globulin [ATG]). The analysis included 35 (18 vedolizumab-treated, 17 placebo-treated) Japanese and 298 (150 vedolizumab-treated, 148 placebo-treated) non-Japanese patients. Lower-GI aGVHD-free survival by day + 180 after allo-HSCT (primary endpoint) was 94% in vedolizumab-treated versus 81% in placebo-treated Japanese patients (HR 0.36; 95% CI 0.03-4.01; P = 0.2) and 84% in vedolizumab-treated versus 70% in placebo-treated non-Japanese patients (HR 0.47; 95% CI 0.28-0.78; P = 0.002). The number of events for the 5 key secondary endpoints (lower-GI aGVHD-free and relapse-free survival, Grade C-D aGVHD-free survival, non-relapse mortality, overall survival, and Grade B-D aGVHD-free survival) by day + 180 was lower in vedolizumab- versus placebo-treated Japanese patients. No safety concerns were identified for vedolizumab use as lower-GI aGVHD prophylaxis in Japanese patients.

Temporal changes in corticosteroid dose during ibrutinib treatment in patients with cGVHD and pulmonary involvement.
Masako Toyosaki, Shinichiro Machida, Daisuke Tomizawa, Masaya Okada, Masashi Sawa, Yasunori Ueda, Ai Omi, Yosuke Koroki, Takanori Teshima
International journal of hematology, 121, 3, 388, 396, 2025年03月, ［国内誌］
英語, 研究論文（学術雑誌）, The GVH3001 study assessed the efficacy and safety of ibrutinib in Japanese patients with steroid-dependent or -refractory chronic graft-versus-host disease (cGVHD). However, the effects of ibrutinib on lung function and reduction in corticosteroid dose, which is a measurable factor associated with improved quality of life, could not be adequately assessed in patients who initially presented with lung involvement. This post hoc analysis aimed to evaluate temporal changes in daily corticosteroid dose, as well as effectiveness outcomes based on lung function and symptom burden (percent predicted forced expiratory volume in 1 s [%FEV1] and Lee cGVHD Symptom Scale lung subscale score, respectively) in the subgroup of patients with cGVHD who had lung involvement at baseline. Seven of the 19 patients in the GVH3001 study had lung involvement at baseline. The daily corticosteroid dose for cGVHD decreased in five of these patients, and %FEV1 remained relatively stable in two patients but increased to > 80% in one patient. Lee cGVHD Symptom Scale scores were relatively stable throughout the study in patients with lung involvement. Ibrutinib may allow corticosteroid dose reduction without worsening lung function or increasing symptom burden in previously treated patients with cGVHD and associated lung involvement.

CML With Mutant ASXL1 Showed Decreased Sensitivity to TKI Treatment via Upregulation of the ALOX5-BLTR Signaling Pathway.
Naoki Miyashita, Masahiro Onozawa, Kohei Kasahara, Toshihiro Matsukawa, Yasuhito Onodera, Kohjin Suzuki, Tomoiku Takaku, Takanori Teshima, Takeshi Kondo
Cancer science, 2025年02月04日, ［国際誌］
英語, 研究論文（学術雑誌）, In this study, the mechanisms of tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML) were investigated focusing additional sex combs-like 1 (ASXL1) gene mutations and their downstream effects. While TKIs have improved the prognosis of CML, some patients have shown resistant to therapy. Cases with mutations in epigenome-related genes such as ASXL1 are known to have a poor prognosis, but the underlying mechanisms of the poor prognosis are unclear. We showed that mutated ASXL1 reduces TKI sensitivity in CML cell lines, and RNA microarray analysis revealed that arachidonate 5-lipoxygenase (ALOX5) is a significantly upregulated gene under the conditional expression of mutated ASXL1. Enforced ALOX5 expression induced TKI resistance, while ALOX5 knockout increased TKI sensitivity. ALOX5 downstream signal inhibition by LY293111, a leukotriene B4 receptor (BLTR) antagonist, suppressed AKT phosphorylation and enhanced TKI sensitivity. This study revealed that TKI resistance in CML with ASXL1 mutation was induced via ALOX5 overexpression. ASXL1 mutations may confer a clonal advantage through activation of the AKT pathway following ALOX5 overexpression. While combined use of LY293111 with TKIs and asciminib showed synergistic effects against CML cells, the ALOX5-BLTR signaling pathway is novel therapeutic target for CML patients with mutated ASXL1.

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

Efficacy and safety of mosunetuzumab monotherapy for Japanese patients with relapsed/refractory follicular lymphoma: FLMOON-1.
Hideki Goto, Takahiro Kumode, Yuko Mishima, Keisuke Kataoka, Yoshiaki Ogawa, Nobuhiro Kanemura, Kazuyuki Shimada, Toshiki Uchida, Yukano Kuroe, Atsuko Kawasaki, Jotaro Sato, Takanori Teshima
International journal of clinical oncology, 2024年12月09日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: In a global phase I/II study (GO29781; NCT02500407), single-agent mosunetuzumab had a manageable safety profile and induced durable complete responses in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma, including in patients with R/R follicular lymphoma (FL). In this analysis, the efficacy and safety of mosunetuzumab monotherapy were evaluated in an expansion cohort, FLMOON-1, in Japanese patients with R/R FL who had received  ≥ 2 prior lines of therapy in a phase I study (JO40295, jRCT2080223801). METHODS: Mosunetuzumab was administered intravenously at the recommended phase II dose (with cycle 1 step-up dosing) for eight cycles or up to 17 cycles, or until disease progression or unacceptable toxicity. The pre-specified primary endpoint was Independent Review Facility (IRF)-assessed complete response rate (CRR; as best overall response). Secondary objectives included investigator (INV)-assessed CRR, INV- and IRF-assessed objective response rate (ORR), and safety. RESULTS: At the data cutoff (October 13, 2023), 19 patients (median age 72 years) were evaluated. The IRF-assessed CRR and ORR were 68.4% and 78.9%, respectively; the INV-assessed CRR and ORR were 63.2% and 84.2%, respectively. Grade 3-4 adverse events (AEs) were observed in 89.5% of patients, with a low incidence of AEs leading to mosunetuzumab discontinuation (10.5%) and one fatal AE unrelated to mosunetuzumab. Cytokine release syndrome occurred in 47.4% of patients and were mostly Grade 1 in severity. CONCLUSION: These findings indicate mosunetuzumab has a consistent efficacy and manageable safety profile in Japanese patients with R/R FL compared with previously reported data from the global phase I/II study.

ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies.
Piyanuch Kongtim, Pongthep Vittayawacharin, Jun Zou, Samer Srour, Brian Shaffer, Roman M Shapiro, Ankur Varma, Joseph McGuirk, Bhagirathbhai R Dholaria, Shannon R McCurdy, Amy E DeZern, Nelli Bejanyan, Asad Bashey, Sabine Furst, Luca Castagna, Jacopo Mariotti, Annalisa Ruggeri, Rebeca Bailen, Takanori Teshima, Huang Xiao-Jun, Carmen Bonfim, Fleur Aung, Kai Cao, Paul A Carpenter, Mehdi Hamadani, Medhat Askar, Marcelo Fernandez-Vina, Alin Girnita, Stefan O Ciurea
Transplantation and cellular therapy, 30, 12, 1139, 1154, 2024年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.

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

Ruxolitinib for steroid-refractory chronic graft-versus-host disease: Japanese subgroup analysis of REACH3 study.
Souichi Shiratori, Kentaro Fukushima, Yasushi Onishi, Noriko Doki, Tatsunori Goto, Masaya Okada, Hirohisa Nakamae, Yoshinobu Maeda, Koji Kato, Takayuki Ishikawa, Tadakazu Kondo, Masako Toyosaki, Takashi Ikeda, Naoyuki Uchida, Akio Maki, Fumika Shimada, Takeshi Tajima, Tommaso Stefanelli, Takanori Teshima
International journal of hematology, 120, 6, 705, 716, 2024年12月, ［国内誌］
英語, 研究論文（学術雑誌）, Ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, has demonstrated safety and efficacy in patients with graft-versus-host disease (GvHD). This phase 3 randomized trial (REACH3) evaluated the efficacy and the safety of ruxolitinib 10 mg twice daily compared with investigator-selected best available therapy (BAT) in a subgroup of Japanese patients (n = 37) with steroid-refractory or dependent (SR/D) chronic GvHD. At data cut-off, treatment was ongoing in 17 patients and discontinued in 20. The overall response rate (complete or partial) at week 24 was greater with ruxolitinib than BAT (50% vs. 20%; odds ratio, 4.13 [95% CI, 0.90-18.9]). The best overall response rate (complete or partial response at any time point up to week 24) was higher with ruxolitinib than BAT (68.2% vs. 46.7%; odds ratio, 2.69 [95% CI, 0.66-10.9]). Ruxolitinib led to longer median failure-free survival than BAT (18.6 months vs. 3.7 months; hazard ratio, 0.34; [95% CI, 0.14-0.85]). The most common grade ≥ 3 adverse events up to week 24 were anemia (ruxolitinib: 22.7%; BAT: 6.7%) and pneumonia (22.7% and 20.0%, respectively). Ruxolitinib showed a higher response rate and improvement in failure-free survival in Japanese patients with SR/D chronic GvHD, with a safety profile consistent with the overall study population.

2023年の国内新規診断未治療HIV感染者・AIDS患者における薬剤耐性HIV-1の動向　　　　　　　　　　　　　　　
菊地 正, 西澤 雅子, 椎野 禎一郎, 豊嶋 崇徳, 伊藤 俊広, 林田 庸総, 潟永 博之, 古賀 道子, 長島 真美, 貞升 健志, 佐野 貴子, 宇野 俊介, 谷口 俊文, 猪狩 英俊, 寒川 整, 中島 秀明, 吉野 友祐, 堀場 昌英, 茂呂 寛, 渡邉 珠代, 今橋 真弓, 蜂谷 敦子, 松田 昌和, 重見 麗, 岡崎 玲子, 岩谷 靖雅, 横幕 能行, 渡邊 大, 阪野 文哉, 川畑 拓也, 藤井 輝久, 高田 清式, 中村 麻子, 南 留美, 松下 修三, 仲村 秀太, 小島 潮子, Runtuwene Lucky, 吉村 和久, 杉浦 亙
日本エイズ学会誌, 26, 4, 463, 463, (一社)日本エイズ学会, 2024年11月
日本語

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, 2024年11月
日本語

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, 2024年11月
日本語

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, 2024年11月
日本語

北海道ブロック「HIV/AIDS出張研修」 12年間の実践報告　　　　　　　　　　　　　　　
渡部 恵子, センテノ田村 恵子, 遠藤 知之, 武内 阿味, 熊谷 泰恵, 石田 陽子, 尾谷 ゆか, 山口 みなみ, 北村 末季, 松川 敏大, 長谷川 祐太, 後藤 秀樹, 豊嶋 崇徳, 三宅 亜矢
日本エイズ学会誌, 26, 4, 514, 514, (一社)日本エイズ学会, 2024年11月
日本語

Safety and efficacy of acalabrutinib and obinutuzumab in treatment-naive chronic lymphocytic leukemia: a Japanese phase 1 study.
Jun Takizawa, Takanori Teshima, Daisuke Ennishi, Satoshi Ichikawa, Ritsuro Suzuki, Akira Kojima, Yusuke Takahashi, Nobuya Hayashi, Hisashi Kawasumi, Kosho Murayama, Patricia Cheung, Toshio Kawata, Koji Izutsu
Leukemia & lymphoma, 65, 11, 1586, 1594, 2024年11月, ［国際誌］
英語, 研究論文（学術雑誌）, This report focuses on part 3 of a multicenter, open-label, phase 1 study (NCT03198650) assessing the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of acalabrutinib plus obinutuzumab in Japanese patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL). Ten patients were included; median age was 68 years. With a median treatment duration of 27.2 months, treatment-emergent adverse events (AEs) occurred in all patients (grade ≥3, 70%), and the most common AEs were anemia and headache (40% each). One patient had a grade 4 AE of neutropenia (the only dose-limiting toxicity). PK results suggested no marked effects of concomitant obinutuzumab treatment on the exposure of acalabrutinib. PD assessment indicated that combination therapy provided >98% Bruton tyrosine kinase (BTK) occupancy. Overall response rate (ORR) was 100% with median duration of response (DoR) and median progression-free survival (PFS) not reached. Treatment with acalabrutinib plus obinutuzumab was generally safe and efficacious in adult Japanese patients with TN CLL.

Validation of Left Ventricular Filling Pressure Evaluation by Order of Tricuspid and Mitral Valve Opening in Patients With Atrial Fibrillation.
Hisao Nishino, Michito Murayama, Hiroyuki Iwano, Nobuyuki Kagiyama, Yutaka Nakamura, Yuka Akama, Misako Toki, Sachiko Takamatsu, Taiji Okada, Yasuyuki Chiba, Masahiro Nakabachi, Shinobu Yokoyama, Mana Goto, Yukino Suzuki, Suguru Ishizaka, Ko Motoi, Yoji Tamaki, Hiroyuki Aoyagi, Kosuke Nakamura, Sanae Kaga, Chiaki Watanabe, Kiwamu Kamiya, Toshiyuki Nagai, Takanori Teshima, Toshihisa Anzai
Circulation. Cardiovascular imaging, 17, 11, e017134, 2024年11月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Accurate assessment of left ventricular filling pressure in patients with atrial fibrillation or flutter (AF) remains difficult. A novel 2-dimensional scoring system, visually assessing time difference between mitral valve and tricuspid valve opening (VMT) score, based on temporal analysis of early diastolic valve opening, could be applied to these patients. We aimed to determine the usefulness of the VMT score in patients with AF. METHODS: We analyzed 119 consecutive patients with AF who underwent cardiac catheterization as a derivation cohort. The diagnostic performance of the VMT score was further evaluated in an external data set containing 189 patients with AF. Elevated left ventricular filling pressure was defined as a mean pulmonary arterial wedge pressure ≥15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0, tricuspid valve first; 1, simultaneous; 2, mitral valve first). When the inferior vena cava was dilated, 1 point was added, and the VMT score was finally graded as 0 to 3. Conventional Doppler parameters to estimate left ventricular filling pressure were also measured. RESULTS: Pulmonary arterial wedge pressure was elevated with an increase in the VMT score (0: 10±3, 1: 13±5, 2: 22±7, 3: 27±6 mm Hg; P<0.001), resulting in a significant rise in pulmonary arterial wedge pressure from VMT score 1 to 2. VMT≥2 predicted elevated pulmonary arterial wedge pressure with an accuracy of 87%, and the diagnostic accuracy of the VMT score was significantly higher than that of conventional Doppler parameters (C index, 0.88 versus 0.54-0.68; P<0.001). In addition, VMT ≥2 showed an incremental predictive value over plasma brain natriuretic peptide levels (C index, 0.79-0.93; P<0.001). In the external validation cohort, VMT≥2 demonstrated acceptable accuracy of 72%. CONCLUSIONS: VMT scoring was a useful echocardiographic marker of elevated left ventricular filling pressure and had an incremental benefit over practical biomarkers in patients with AF.

Genome-wide CRISPR screen identifies MAD2L1BP and ANAPC15 as targets for brentuximab vedotin sensitivity in CD30+ peripheral T-cell lymphoma.
Keito Suto, Norio Takei, Keito Yokoyama, Masahiro Chiba, Takashi Ishio, Michiyuki Maeda, Hideki Goto, Tomoyuki Endo, Takanori Teshima, Yibin Yang, Masao Nakagawa
Leukemia, 2024年10月21日, ［国際誌］
英語, 研究論文（学術雑誌）

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

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, 2024年10月
日本語

FLT3阻害薬は投与時期に関わらずFLT3変異AMLの予後を延長する　　　　　　　　　　　　　　　
松川 敏大, 近藤 健, 日高 大輔, 太田 秀一, 金谷 穣, 盛 暁生, 重松 明男, 宮城島 拓人, 柿木 康孝, 橋口 淳一, 山本 聡, 山本 昌代, 若狭 健太郎, 高畑 むつみ, 石原 敏道, 長谷山 美仁, 藤見 章仁, 五十嵐 哲祥, 更科 岳大, 井山 諭, 小林 良二, 酒井 基, 藤本 勝也, 稲村 純季, 蟹澤 祐司, 平林 真介, 小野澤 真弘, 遠藤 知之, 豊嶋 崇徳
日本血液学会学術集会, 86回, O1, 5, (一社)日本血液学会, 2024年10月
英語

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, 2024年10月
英語

ベネトクラクスによる治療を受けた新規診断急性骨髄性白血病の遺伝子変異と予後　　　　　　　　　　　　　　　
宮下 直樹, 小野澤 真弘, 長井 惇, 吉田 匠汰, 木村 弘幸, 横山 翔大, 松川 敏大, 杉田 純一, 日高 大輔, 小笠原 励起, 盛 暁生, 近藤 健, 柿木 康孝, 重松 明男, 若狭 健太郎, 笠原 郁美, 石原 敏道, 橋口 淳一, 武田 紫, 石尾 崇, 酒井 基, 堤 豊, 藤本 勝也, 井山 諭, 小宅 達郎, 豊嶋 崇徳
日本血液学会学術集会, 86回, O2, 3, (一社)日本血液学会, 2024年10月
英語

成人B細胞性急性リンパ性白血病における複雑核型解析　　　　　　　　　　　　　　　
木村 弘幸, 小野澤 真弘, 長井 惇, 吉田 匠汰, 宮下 直樹, 松川 敏大, 盛 暁生, 日高 大輔, 杉田 純一, 柿木 康孝, 堤 豊, 山本 聡, 重松 明男, 橋口 淳一, 井端 淳, 横山 翔大, 若狭 健太郎, 長谷山 美仁, 藤本 勝也, 石原 敏道, 酒井 基, 平林 真介, 小宅 達郎, 近藤 健, 豊嶋 崇徳
日本血液学会学術集会, 86回, O3, 3, (一社)日本血液学会, 2024年10月
英語

国内HIV-1伝播クラスタの2022年の動向 薬剤耐性HIV調査ネットワークによるSPHNCS年報
椎野 禎一郎, 潟永 博之, 今橋 真弓, 渡邊 大, 南 留美, 蜂谷 敦子, 西澤 雅子, 林田 庸総, 吉田 繁, 豊嶋 崇徳, 伊藤 俊広, 古賀 道子, 貞升 健志, 佐野 貴子, 宇野 俊介, 谷口 俊文, 猪狩 英俊, 寒川 整, 中島 秀明, 吉野 友祐, 堀場 昌英, 茂呂 寛, 渡邉 珠代, 阪野 文哉, 川畑 拓也, 藤井 輝久, 高田 清式, 中村 麻子, 仲村 秀太, 松下 修三, 吉村 和久, 杉浦 亙, 菊地 正
日本エイズ学会誌, 26, 3, 139, 150, (一社)日本エイズ学会, 2024年08月
日本語

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, 2024年08月
日本語

Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial.
Yi-Bin Chen, Mohamad Mohty, Robert Zeiser, Takanori Teshima, Omer Jamy, Johan Maertens, Duncan Purtill, Jingjing Chen, Hong Cao, Guillermo Rossiter, Johan Jansson, Yngvar Fløisand
Nature medicine, 30, 8, 2277, 2287, 2024年08月, ［国際誌］
英語, 研究論文（学術雑誌）, Acute graft-versus-host disease (aGVHD) of the lower gastrointestinal (GI) tract is a major cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab is a gut-selective anti-α4β7 integrin monoclonal antibody that reduces gut inflammation by inhibiting migration of GI-homing T lymphocytes. The efficacy and safety of vedolizumab added to standard GVHD prophylaxis (calcineurin inhibitor plus methotrexate/mycophenolate mofetil) was evaluated for prevention of lower-GI aGVHD after unrelated donor allo-HSCT in a randomized, double-blind, placebo-controlled phase 3 trial. Enrollment closed early during the COVID-19 pandemic with 343 patients randomized (n = 174 vedolizumab, n = 169 placebo), and 333 received ≥1 intravenous dose of 300 mg vedolizumab (n = 168) or placebo (n = 165) and underwent allo-HSCT. The primary end point was met; Kaplan-Meier (95% confidence interval) estimated rates of lower-GI aGVHD-free survival by day +180 after allo-HSCT were 85.5% (79.2-90.1) with vedolizumab versus 70.9% (63.2-77.2) with placebo (hazard ratio, 0.45; 95% confidence interval, 0.27-0.73; P < 0.001). For the 5 key secondary efficacy end points analyzed by day +180 after allo-HSCT, rates of lower-GI aGVHD-free and relapse-free survival and grade C-D aGVHD-free survival were significantly higher with vedolizumab versus placebo. No significant treatment differences were found for the other key secondary end points of non-relapse mortality, overall survival and grade B-D aGVHD-free survival, respectively. Incidence of treatment-related serious adverse events analyzed in patients receiving ≥1 dose of study treatment (n = 334) was 6.5% (n = 11 of 169) vedolizumab versus 8.5% (n = 14 of 165) placebo. When added to standard calcineurin inhibitor-based GVHD prevention, lower-GI aGVHD-free survival was significantly higher with vedolizumab versus placebo. ClinicalTrials.gov identifier: NCT03657160 .

パテントブルーとインドシアニングリーンが混濁・溶血判定に与える影響　　　　　　　　　　　　　　　
中野 恵一, 安田 慶子, 山下 直樹, 後藤 秀樹, 豊嶋 崇徳
医療検査と自動化, 49, 4, 390, 390, (一社)日本医療検査科学会, 2024年08月
日本語

国内HIV-1伝播クラスタの2022年の動向 薬剤耐性HIV調査ネットワークによるSPHNCS年報　　　　　　　　　　　　　　　
椎野 禎一郎, 潟永 博之, 今橋 真弓, 渡邊 大, 南 留美, 蜂谷 敦子, 西澤 雅子, 林田 庸総, 吉田 繁, 豊嶋 崇徳, 伊藤 俊広, 古賀 道子, 貞升 健志, 佐野 貴子, 宇野 俊介, 谷口 俊文, 猪狩 英俊, 寒川 整, 中島 秀明, 吉野 友祐, 堀場 昌英, 茂呂 寛, 渡邉 珠代, 阪野 文哉, 川畑 拓也, 藤井 輝久, 高田 清式, 中村 麻子, 仲村 秀太, 松下 修三, 吉村 和久, 杉浦 亙, 菊地 正
日本エイズ学会誌, 26, 3, 139, 150, (一社)日本エイズ学会, 2024年08月
日本語

Generation of recombinant viruses directly from clinical specimens of COVID-19 patients.
Hirotaka Yamamoto, Tomokazu Tamura, Takaya Ichikawa, Yudai Taguchi, Kento Mori, Satoshi Oguri, Rigel Suzuki, Saori Suzuki, Takanori Teshima, Takasuke Fukuhara
Journal of clinical microbiology, 62, 7, e0004224, 2024年07月16日, ［国際誌］
英語, 研究論文（学術雑誌）, UNLABELLED: Rapid characterization of the causative agent(s) during a disease outbreak can aid in the implementation of effective control measures. However, isolation of the agent(s) from crude clinical samples can be challenging and time-consuming, hindering the establishment of countermeasures. In the present study, we used saliva specimens collected for the diagnosis of SARS-CoV-2-a good example of a practical target-and attempted to characterize the virus within the specimens without virus isolation. Thirty-four saliva samples from coronavirus disease 2019 patients were used to extract RNA and synthesize DNA amplicons by PCR. New primer sets were designed to generate DNA amplicons of the full-length spike (S) gene for subsequent use in a circular polymerase extension reaction (CPER), a simple method for deriving recombinant viral genomes. According to the S sequence, four clinical specimens were classified as BA. 1, BA.2, BA.5, and XBB.1 and were used for the de novo generation of recombinant viruses carrying the entire S gene. Additionally, chimeric viruses carrying the gene encoding GFP were generated to evaluate viral propagation using a plate reader. We successfully used the RNA purified directly from clinical saliva samples to generate chimeric viruses carrying the entire S gene by our updated CPER method. The chimeric viruses exhibited robust replication in cell cultures with similar properties. Using the recombinant GFP viruses, we also successfully characterized the efficacy of the licensed antiviral AZD7442. Our proof-of-concept demonstrates the novel utility of CPER to allow rapid characterization of viruses from clinical specimens. IMPORTANCE: Characterization of the causative agent(s) for infectious diseases helps in implementing effective control measurements, especially in outbreaks. However, the isolation of the agent(s) from clinical specimens is often challenging and time-consuming. In this study, saliva samples from coronavirus disease 2019 patients were directly subjected to purifying viral RNA, synthesizing DNA amplicons for sequencing, and generating recombinant viruses. Utilizing an updated circular polymerase extension reaction method, we successfully generated chimeric SARS-CoV-2 viruses with sufficient in vitro replication capacity and antigenicity. Thus, the recombinant viruses generated in this study were applicable for evaluating the antivirals. Collectively, our developed method facilitates rapid characterization of specimens circulating in hosts, aiding in the establishment of control measurements. Additionally, this approach offers an advanced strategy for controlling other (re-)emerging viral infectious diseases.

術中投与色素の混濁指数への影響 パテントブルーが混濁指数に正誤差を示した一例　　　　　　　　　　　　　　　
中野 恵一, 清宮 正徳, 安田 慶子, 山下 直樹, 後藤 秀樹, 豊嶋 崇徳
臨床化学, 53, Suppl.1, 162, 162, (一社)日本臨床化学会, 2024年07月
日本語

Real-World Outcomes of Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Japan: Retrospective Analysis of Transplant Registry Unified Management Program Registry: GVHD outcomes after allo-HSCT.
Junya Kanda, Takaya Mitsuyoshi, Masatoshi Sakurai, Hisakazu Nishimori, Makoto Murata, Naoyuki Uchida, Noriko Doki, Yoshihiro Inamoto, Tetsuya Nishida, Masatsugu Tanaka, Yuta Katayama, Tetsuya Eto, Ken-Ichi Matsuoka, Satoshi Yoshihara, Masashi Sawa, Toshiro Kawakita, Gyungjin Jun, Mio Kurata, Tatsuo Ichinohe, Takahiro Fukuda, Takanori Teshima, Yoshiko Atsuta, Seitaro Terakura
Transplantation and cellular therapy, 2024年07月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapeutic option for patients with hematological malignancies. However, the development of graft-versus-host disease (GVHD) after allo-HSCT remains a challenge. Although systemic steroid therapy is the established first-line therapy for acute GVHD (aGVHD) and chronic GVHD (cGVHD), many patients are unresponsive or resistant to corticosteroid therapy, and the response is insufficient. OBJECTIVE: To evaluate the clinical characteristics of patients who developed aGVHD and cGVHD after allo-HSCT. STUDY DESIGN: This noninterventional, retrospective study used large national registry data from the Transplant Registry Unified Management Program. The study included 29,690 patients with hematological diseases who underwent their first allo-HSCT between January 2010 and December 2019. The primary endpoints of this study were the cumulative incidence of aGVHD and cGVHD. The secondary endpoints were overall survival (OS) and non-relapse mortality (NRM) of patients with aGVHD and cGVHD and OS and NRM of patients who received second-line therapy for aGVHD. RESULTS: Of 29,690 patients who underwent allo-HSCT, 2,807, 6,167, 10,556, 774, and 9,339 patients received related bone marrow (RBM), related peripheral blood (RPB), unrelated bone marrow, unrelated peripheral blood (UPB), and unrelated cord blood, respectively. The cumulative incidence of aGVHD (grades II-IV) at 100 days was high after the related and unrelated mismatched transplantation. Furthermore, response rate for the first- and second-line therapy for aGVHD was low in the RBM/RPB-mismatched (59.6%/61.6%) and UPB-mismatched subgroup (45.5%), respectively. The 3-year NRM in patients with aGVHD was high in the RPB and UPB mismatched subgroups (37.9% and 31.2%, respectively). CONCLUSION: Developing a novel treatment for steroid-refractory aGVHD is necessary to improve transplant outcomes, particularly for patients undergoing HLA-mismatched transplantation.

Ruxolitinib in steroid-refractory acute graft-vs-host disease: Japanese subgroup analysis of the randomized REACH2 trial.
Takanori Teshima, Yasushi Onishi, Koji Kato, Shuichi Taniguchi, Koichi Miyamura, Kentaro Fukushima, Jun Kato, Takayuki Ishikawa, Noriko Doki, Hirohisa Nakamae, Yoshinobu Maeda, Yoshihiro Inamoto, Masaya Okada, Akio Maki, Fumika Shimada, Takeshi Tajima, Monika Wroclawska, Robert Zeiser, Makoto Onizuka
International journal of hematology, 120, 1, 106, 116, 2024年07月, ［国内誌］
英語, 研究論文（学術雑誌）, Acute graft-versus-host disease (aGvHD) is a major complication after allogeneic hematopoietic stem cell transplantation in Japan and other countries. Nearly one-third of patients do not respond to standard systemic steroid therapy and no standard second-line treatment has been established in Japan. We report efficacy and safety findings of ruxolitinib versus best available therapy (BAT) from a subgroup analysis of the international, phase 3 REACH2 study in Japanese patients with steroid-refractory aGvHD. The primary endpoint was overall response rate (ORR) at day 28. Overall, 9 patients received ruxolitinib and 21 received BAT. The ORR at day 28 (88.9% vs 52.4%) and durable ORR at day 56 (66.7% vs 28.6%) were higher with ruxolitinib versus BAT. The estimated cumulative incidence of loss of response at 6 months was 12.5% with ruxolitinib and 18.2% with BAT. The median failure-free survival was longer with ruxolitinib versus BAT (2.73 vs 1.25 months). The most common adverse events up to day 28 in the ruxolitinib and BAT groups were anemia (55.6% vs 19.0%) and thrombocytopenia (44.4% vs 4.8%, respectively). Ruxolitinib showed better efficacy outcomes and a consistent safety profile compared with BAT in the Japanese subgroup, and the findings were consistent with overall study results.

An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD.
Yoshihiro Inamoto, Koji Kato, Toshiro Kawakita, Yasushi Onishi, Ken-Ichi Matsuoka, Soichi Shiratori, Kazuhiro Ikegame, Nobuhiro Hiramoto, Masako Toyosaki, Yuta Katayama, Shun Murayama, Yuji Sasagawa, Yoshinobu Maeda, Kiyohiko Hatake, Takanori Teshima
American journal of hematology, 2024年06月27日, ［国際誌］
英語, 研究論文（学術雑誌）, Belumosudil mesylate is a selective Rho-associated coiled-coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open-label, single-arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid-dependent/steroid-resistant chronic graft-versus-host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7-97.0), and the lower limit of the 95% CI exceeded the pre-defined threshold of 25%. The Kaplan-Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46-90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90-8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0-51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure-free and overall survival were not reached. Treatment-emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug-related. There were no drug-related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid-dependent/steroid-resistant cGVHD was effective, with no new safety concerns.

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, 144, 8, 904, 913, 2024年06月21日, ［国際誌］
英語, 研究論文（学術雑誌）, Graft-versus-host disease (GVHD) is a major life-threatening complication that occurs after allogeneic hematopoietic cell transplantation (HCT). While adult tissue stem cells have been identified as targets of GVHD in the skin and gut, their role in hepatic GVHD is yet to be clarified. In the current study, we explored the fate of bile duct stem cells (BDSCs), capable of generating liver organoids in vitro, during hepatic GVHD after allogeneic HCT. We observed a significant expansion of biliary epithelial cells (BECs) upon injury early after allogeneic HCT. Organoid-forming efficiency from the bile duct was also significantly increased early after allogeneic HCT. Subsequently, the organoid-forming efficiency from bile ducts was markedly decreased in association with the reduction of BECs and the elevation of plasma concentrations of bilirubin, suggesting that GVHD targets BDSCs and impairs the resilience of BECs. The growth of liver organoids in the presence of liver-infiltrating mononuclear cells from allogeneic recipients, but not from syngeneic recipients, significantly reduced in a TGF--dependent manner. Administration of SB-431542, an inhibitor of TGF-β signaling, from day 14 to day 28 protected organoid-forming BDSCs against GVHD and mitigated biliary dysfunction after allogeneic HCT, suggesting that BDSCs are a promising therapeutic target for hepatic GVHD.

Event-free survival at 36 months is a suitable endpoint for diffuse large B-cell lymphoma patients treated with immunochemotherapy: real-world evidence from the North Japan Hematology Study Group.
Koh Izumiyama, Tasuku Inao, Hideki Goto, Shinpei Harada, Hajime Senjo, Keito Suto, Junichi Hashiguchi, Reiki Ogasawara, Tomoyuki Saga, Tetsuyuki Igarashi, Kentaro Wakasa, Ikumi Kasahara, Yukari Takeda, Keisuke Yamaguchi, Akio Shigematsu, Mutsumi Takahata, Katsuya Fujimoto, Yoshihito Haseyama, Takahiro Nagashima, Hajime Sakai, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Isao Yokota, Takanori Teshima
Haematologica, 2024年06月13日, ［国際誌］
英語, 研究論文（学術雑誌）, Information regarding follow-up duration after treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL) is important. However, a clear endpoint has yet to be established. We totally enrolled 2182 patients newly diagnosed with DLBCL between 2008 and 2018. The median age of the patients was 71 years. All patients were treated with rituximab- and anthracycline-based chemotherapies. Each overall survival (OS) was compared with the age- and sex-matched Japanese general population (GP) data. At a median follow-up of 3.4 years, 985 patients experienced an event and 657 patients died. Patients who achieved an event-free survival (EFS) at 36 months (EFS36) had an OS equivalent to that of the matched GP (standard mortality ratio [SMR], 1.17; P=0.1324), whereas those who achieved an EFS24 did not have an OS comparable to that of the matched GP (SMR, 1.26; P=0.0095). Subgroup analysis revealed that relatively old patients (>60 years), male patients, those with limited-stage disease, those with a good performance status, and those with low levels of soluble interleukin 2 receptor already had a comparable life expectancy to the matched GP at an EFS24. In contrast, relatively young patients had a shorter life expectancy than matched GP, even with an EFS36. In conclusion, an EFS36 was shown to be a more suitable endpoint for newly diagnosed DLBCL patients than an EFS24. Of note, younger patients require a longer EFS period than older patients in order to obtain an equivalent life expectancy to the matched GP.

イムノクロマト法によるHIT抗体測定の検討
宇佐美 貴之, 安本 篤史, 李 明海, 畑瀬 正尚, 早坂 光司, 村上 望, 山下 亜妃子, 山下 直樹, 後藤 秀樹, 豊嶋 崇徳
日本検査血液学会雑誌, 25, 学術集会, S205, S205, (一社)日本検査血液学会, 2024年06月
日本語

Novel CAR T cell therapies for patients with large B cell lymphoma.
Hideki Goto, Masahiro Onozawa, Takanori Teshima
International journal of hematology, 2024年05月25日, ［国内誌］
英語, 研究論文（学術雑誌）, Approximately 60-70% of patients with large B cell lymphoma (LBCL) achieve long-term remission or a cure after initial treatment. However, patients who relapse or are refractory to initial treatment have a poor prognosis. Chimeric antigen receptor (CAR) T cell therapy has recently attracted attention for its potential to provide a cure or long-term remission even for LBCL that has relapsed or is refractory to conventional chemotherapy. Currently, three CAR T cell products are clinically available for LBCL: tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel). These CAR T cell products were initially approved as third- or later-line therapies worldwide. Recently, axi-cel and liso-cel have become feasible as second-line therapies for patients with early relapsed or refractory disease after first-line chemotherapy. Although a large body of data on CAR T cell therapy has been accumulated, the clinical question of how to choose between these three available CAR T cell products has yet to be resolved. The appropriate approach to treatment selection for patients who relapse after CAR T cell therapy also remains unclear. This review discusses treatment strategies to maximize the benefits of CAR T cell therapy.

American Society for Transplantation and Cellular Therapy International Affairs Committee: Report of the 4th Workshop on Quality as a Development Tool for Hematopoietic Cell Transplantation Programs at the 2023 Tandem BMT Meetings.
Pablo Ramirez, Yoshiko Atsuta, Amal Alseraihy, Shinichiro Okamoto, Takanori Teshima, Mahmoud Aljurf, Navneet S Majhail, Damiano Rondelli, Nelson Chao, Mary E Flowers
Transplantation and cellular therapy, 30, 5, 468, 474, 2024年05月, ［国際誌］
英語, We provide a summary of the 4th ASTCT International Workshop with presentations from experts from Chile ("Setting Up a Transplantation Program in Chile," by Dr Pablo Ramirez), Saudi Arabia ("Developing Quality Programs in North Africa," by Dr Amal Alseraihy), and Japan ("The Japanese Transplant Registry Unified Management Program [TRUMP]: Current Issues and the Future," by Dr Yoshiko Atsuta). Workshop objectives included: (1) recognizing the benefits and importance for low- and middle-income countries of developing quality criteria and programs beyond existing accreditation programs, such as the Foundation for the Accreditation of Cellular Therapy (FACT) and the Joint Accreditation Committee ISCT-Europe and EBMT (JACIE); (2) describing the relationships among monitoring outcomes, including mortality, improvement of care, data reporting, and associated costs; and (3) reviewing how quality structures have been implemented and are improving care worldwide.

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update.
Martin Dreyling, Nathan Hale Fowler, Michael Dickinson, Joaquin Martinez-Lopez, Arne Kolstad, Jason Butler, Monalisa Ghosh, Leslie Popplewell, Julio C Chavez, Emmanuel Bachy, Koji Kato, Hideo Harigae, Marie José Kersten, Charalambos Andreadis, Peter A Riedell, P Joy Ho, José Antonio Pérez-Simón, Andy I Chen, Loretta J Nastoupil, Bastian von Tresckow, Andrés José María Ferreri, Takanori Teshima, Piers E M Patten, Joseph P McGuirk, Andreas L Petzer, Fritz Offner, Andreas Viardot, Pier Luigi Zinzani, Ram Malladi, Ines Paule, Aiesha Zia, Rakesh Awasthi, Xia Han, Davide Germano, Darragh O'Donovan, Roberto Ramos, Harald J Maier, Aisha Masood, Catherine Thieblemont, Stephen J Schuster
Blood, 143, 17, 1713, 1725, 2024年04月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor-positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.

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

Patent blue interferes with the measurement of lipemia index in a patient with sentinel lymph node.
Keiichi Nakano, Masanori Seimiya, Kojiro Yamazaki, Keiko Yasuda, Naoki Yamashita, Hideki Goto, Takanori Teshima
Laboratory medicine, 2024年04月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Lipids interfere with absorbance measurements conducted using colorimetric methods. To monitor lipemia, some systems measure absorbance using an analyzer. This report describes a novel case of interference with the lipemia index without lipemia. A 64-year-old woman with giant basal cell carcinoma underwent resection and sentinel lymph node biopsy. The patient had been subcutaneously injected with patent blue during sentinel lymph node resection. After surgery, her serum and urine were yellow-green, and the lipemia index, calculated by measuring absorbance at 658 nm (main wavelength) and 694 nm (secondary wavelength) using a JCA-BM8040 chemistry analyzer, was high. The absorbance spectrum of the patient's serum and patent blue solution were compared to determine the cause of the high lipemia index. The patient's serum and the patent blue solution showed absorption at wavelengths between 540 and 698 nm. Moreover, the absorbance was concentration-dependent for patent blue. These results thus indicated that the patient's serum contained patent blue. Here, we report a case wherein patent blue affected the lipemia index. Thus, it must be noted that patent blue injection may yield inaccurate results when evaluating lipemia index.

Relative impact of THPO mutation causing hereditary thrombocythemia.
Hiroyuki Kimura, Masahiro Onozawa, Toshihiro Matsukawa, Hideki Goto, Takeshi Kondo, Takanori Teshima
Experimental hematology, 104208, 104208, 2024年03月26日, ［国際誌］
英語, 研究論文（学術雑誌）, Germline mutations of THPO were reported as causes of hereditary thrombocythemia. Six previously reported distinct sites of the mutation were clustered at the 5'-untranslated region or the exon 3 splicing donor site of the THPO gene. Each mutation was identified in an independent pedigree and the difference in the mutations were not compared. We cloned 6 distinct THPO mutations (THPO c.-47delG, THPO c.-31G>T, THPO c.13G>A, THPO c.13+1G>A, THPO c.13+2T>C, and THPO c.13+5G>A) and compared the molecular mechanisms that underlie the increased production of THPO protein. At the transcript level, all of the mutations except THPO c.-47delG showed an exon 3 skipping transcript including 2 mutations (THPO c.-31G>T and THPO c.13+5G>A) that were distant from the splicing donor site. THPO c.-47delG showed the same full-length transcript as that of the wild-type transcript. At the protein level, all mutations resulted in a higher level of production of THPO protein compared to wild-type THPO. There are only two distinct patterns of mechanisms for increased production of THPO: 1) exon 3 skipping that deleted upstream suppressive open reading frame (ORF) 7 and 2) one base deletion that shifted ORF7 to connect to the initial codon of THPO in-frame. The common mechanisms of hereditary thrombocytosis due to THPO mutation are unleashed THPO translation that is usually suppressed by upstream out-of-frame ORF7.

【血小板減少症の診かた】薬剤による血小板減少症　　　　　　　　　　　　　　　
安本 篤史, 豊嶋 崇徳
日本医師会雑誌, 152, 12, 1361, 1364, (公社)日本医師会, 2024年03月
日本語

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, 2024年02月13日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

肺小細胞癌の治療中に白血球増多と線維素性心外膜炎を認めた一例　　　　　　　　　　　　　　　
山内 智仁, 種井 善一, 長井 淳, 小田 義崇, 菊池 遼, 小野澤 真弘, 津田 真寿美, 田中 敏, 豊島 崇徳, 田中 伸哉
日本病理学会会誌, 113, 1, 463, 463, (一社)日本病理学会, 2024年02月
日本語

ハイブリッド視察によるI&A受審を経験して
伊藤 誠, 増田 裕弥, 南 昭子, 佐々木 麻記, 山下 直樹, 渡邊 千秋, 後藤 秀樹, 豊嶋 崇徳
日本輸血細胞治療学会誌, 70, 1, 51, 51, (一社)日本輸血・細胞治療学会, 2024年02月
日本語

Novel stratification for newly diagnosed acute myeloid leukaemia treated with venetoclax-based therapy in the real world: Hokkaido Leukemia Net Study.
Naoki Miyashita, Masahiro Onozawa, Toshihiro Matsukawa, Akio Mori, Daisuke Hidaka, Koichiro Minauchi, Akio Shigematsu, Junichi Hashiguchi, Tetsuyuki Igarashi, Yasutaka Kakinoki, Yutaka Tsutsumi, Makoto Ibata, Kentaro Wakasa, Katsuya Fujimoto, Toshimichi Ishihara, Hajime Sakai, Satoshi Iyama, Tatsuo Oyake, Takeshi Kondo, Takanori Teshima
British journal of haematology, 2024年01月18日, ［国際誌］
英語, 研究論文（学術雑誌）

Evaluation of the Loopamp SARS-CoV-2 detection kit using saliva for the detection of SARS-CoV-2 Omicron
Oguri Satoshi, Iwasaki Sumio, Inao Tasuku, Yokota Isao, Murakami Kaoru, Tanaka Kumiko, Hayasaka Kasumi, Fujisawa Shinichi, Watanabe Chiaki, Konno Satoshi, Murakami Masaaki, Teshima Takanori
Laboratory Medicine International, 3, 3, 70, 73, Japanese Society of Laboratory Medicine, 2024年
英語, Aims: The Omicron variant of SARS-CoV-2 spreads more rapidly than ancestral lineages. Reverse-transcription loop-mediated isothermal amplification (RT-LAMP) provides results more rapidly than reverse-transcription
polymerase chain reaction (RT-PCR). However, the reliability in detecting omicrons variant is still unclear due
to possible differences in target sequences.

Methods: Fifty-one saliva specimens, which were positive for the Omicron variant SARS-CoV-2 by real-time RT-PCR and sequencing of the S region, were subjects for this study. The RT-LAMP assay was performed using
the Loopamp SARS-CoV-2 detection kit with (n=51) or without it (n=50).

Results: The RT-LAMP assay following RNA extraction from saliva specimens had a sensitivity of 100% (95%CI: 93.0–100.0%) with 0.969 Kendall’s coefficient of concordance between LAMP threshold time and PCR cycle
threshold value. Forty-five of fifty (90.0%, 95%CI: 78.2–96.7%) specimens positive were also positive by RTLAMP
without RNA extraction.

Conclusions: The Omicron variant was effectively detected in saliva by RT-LAMP using saliva specimens and RNA extraction could improve its efficacy.

Hereditary thrombocythemia due to splicing donor site mutation of THPO in a Japanese family.
Hiroyuki Kimura, Masahiro Onozawa, Junichi Hashiguchi, Daisuke Hidaka, Minoru Kanaya, Toshihiro Matsukawa, Hiromi Okada, Takeshi Kondo, Yoshihiro Matsuno, Takanori Teshima
Annals of hematology, 103, 1, 89, 96, 2024年01月, ［国際誌］
英語, 研究論文（学術雑誌）, Thrombopoietin (THPO) is an essential factor for platelet production. Hereditary thrombocythemia (HT) is caused by a germline mutation of THPO, MPL, or JAK2 and is inherited in an autosomal-dominant manner. We identified a Japanese family with HT due to a point mutation of the splicing donor site of the THPO gene (THPO c.13 + 1G > A). Bone marrow biopsy showed increased megakaryocytes mimicking essential thrombocythemia. One affected family member developed chronic myeloid leukemia. We cloned the mutation and developed mutated and wild type THPO expression vectors. Molecular analysis showed that the mutation causes an exon 3 skipping transcript of THPO that abrogates a suppressive untranslated upstream open reading frame. Although the transcript levels of THPO mRNA were comparable, mutated transcripts were more efficiently translated and THPO protein expression was significantly higher than that of the wild type.

Whole genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in Adult T-cell leukemia/lymphoma.
Masahiro Chiba, Joji Shimono, Keito Suto, Takashi Ishio, Tomoyuki Endo, Hideki Goto, Hiroo Hasegawa, Michiyuki Maeda, Takanori Teshima, Yibin Yang, Masao Nakagawa
Blood, 2023年12月24日, ［国際誌］
英語, 研究論文（学術雑誌）, Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis and limited treatment options. Programmed cell death ligand 1(PD-L1) is recognized to be involved in the pathobiology of ATLL. However, what molecules control PD-L1 expression and whether genetic or pharmacological intervention might modify PD-L1 expression in ATLL cells is still unknown. In order to comprehend the regulatory mechanisms of PD-L1 expression in ATLL cells, we performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening in this work. In ATLL cells, we discovered that the neddylation-associated genes NEDD8, NAE1, UBA3, and CUL3 negatively regulated PD-L1 expression while STAT3 positively did so in ATLL cells. We verified, in line with the genetic results, that treatment with the JAK1/2 inhibitor ruxolitinib or the neddylation pathway inhibitor pevonedistat resulted in a decrease in PD-L1 expression in ATLL cells or an increase in it. It is significant that these results held true regardless of whether ATLL cells had the PD-L1 3' structural variant, a known genetic anomaly that promotes PD-L1 overexpression in certain primary ATLL patients. Pevonedistat alone showed cytotoxicity for ATLL cells, but compared to each single modality, pevonedistat improved the cytotoxic effects of the anti-PD-L1 monoclonal antibody Avelumab and chimeric antigen receptor T-cells targeting PD-L1 in vitro. As a result, our work provided insight into a portion of the complex regulatory mechanisms governing PD-L1 expression in ATLL cells and demonstrated the in vitro preliminary preclinical efficacy of PD-L1-directed immunotherapies by using pevonedistat to upregulate PD-L1 in ATLL cells.

Posttransplant cyclophosphamide in unrelated and related peripheral blood stem cell transplantation from HLA-matched and 1 allele mismatched donor.
Junichi Sugita, Takashi Kuroha, Jun Ishikawa, Tetsuya Eto, Kentaro Fukushima, Isao Yokota, Koichi Akashi, Shuichi Taniguchi, Mine Harada, Takanori Teshima
Bone marrow transplantation, 2023年12月19日, ［国際誌］
英語, 研究論文（学術雑誌）, Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been increasingly used in HLA-haploidentical transplantation and recent studies also demonstrated the efficacy of PTCy in HLA-matched transplantation. We conducted a prospective multicenter phase II study to evaluate the safety and efficacy of PTCy with tacrolimus and mycophenolate mofetil in 43 patients who underwent HLA-matched (n = 21), 1 allele mismatched (n = 20), or 2 allele mismatched (n = 2) peripheral blood stem cell transplantation (PBSCT) following myeloablative (n = 28) or reduced-intensity (n = 15) conditioning. The incidence of grade III-IV acute GVHD at 100 days was 2.3%. The incidences of grades II-IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 16.3%, 14.0%, and 4.7%, respectively. Overall survival, disease-free survival, and non-relapse mortality at 2 years were 75.3%, 74.0%, and 7.0%, respectively. GVHD-free, relapse-free survival at 2 years was 67.0%. The rate of off-immunosuppressants in patients who survived without relapse at 2 years was 85.4%. These results indicate that PTCy is a valid option for GVHD prophylaxis in both HLA-matched and HLA 1-2 allele mismatched PBSCT.

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma.
Yutaka Tsutsumi, Shinichi Ito, Fuka Horikita, Asako Moriki, Takanori Teshima
Molecular and clinical oncology, 19, 6, 96, 96, 2023年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Most hematologic diseases are immunosuppressed, either by the disease itself or by treatment. As such, the implementation of vaccination is largely at the discretion of the attending physician. In this context, an objective measure is needed, therefore the index of vaccination against coronavirus disease 2019 (COVID-19) in B-cell lymphomas treated with antibody therapy against CD20 (including after the completion of therapy) was examined. A total of 40 patients with B-cell lymphoma during or after antibody therapy against CD20 were vaccinated twice with the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer, Inc. and BioNTech SE.) at 3-week intervals and then again six months later with the same vaccine or mRNA-1273 (Moderna, Inc.). Antibody testing was conducted ~1 month after the third vaccination. Analysis was performed using the antibody titers to the anti-spike immunoglobulin assay, with a titer of 0.8 U/ml or higher (considered positive) and a titer of 264 U/ml or higher (considered the value at which the efficacy of the vaccine can be fully expected). Significant factors of antibody acquisition were identified when i) antibody titers were 0.8 U/ml or higher (CD4 ≥400/µl), ii) no anti-CD20 antibody maintenance therapy was undertaken (CD19 ≥100/µl), iii) patients were not on treatment (CD4 ≥400/µl), or 4) at least six months had passed since treatment ended (CD19 ≥100/µl). When antibody titers were 264 U/ml or higher, the treatment method, the stage of the primary disease and other factors related to the condition treatment method of the patient were relevant. When these were analyzed by multivariate analysis, the significant factor when antibody titers were set to 0.8 U/ml was CD19 ≥100/µl. In contrast, when setting them to 264 U/ml or higher, CD4 ≥400/µl was not significant, but there was a tendency for it to be related. The findings of the present study on vaccine-induced antibody acquisition in patients with B-cell lymphoma indicated that it is desirable to have a CD19 titer of at least 100/µl and a CD4 titer of at least 400/µl (both conditions should be met), and that no maintenance therapy with anti-CD20 antibody should be administered for at least six months after the last treatment or completion of the treatment. Interestingly, when the criteria for antibody titers were compared between 0.8 U/ml, where antibody titer is detected, and 264 U/ml, where vaccine efficacy is expected, several key factors were different. It is possible that these key factors may change depending on the antibody titer used as a criterion.

Genetic background of thrombocytosis in mice mimicking hereditary thrombocytosis in humans.
Hiroyuki Kimura, Masahiro Onozawa, Takanori Teshima
Platelets, 34, 1, 2276697, 2276697, 2023年12月, ［国際誌］
英語, 研究論文（学術雑誌）

A Longitudinal Study of the Physical Characteristics, Muscle-Tendon Structure Properties, and Skeletal Age in Preadolescent Boys.
Keitaro Kubo, Takanori Teshima, Norikazu Hirose, Naoya Tsunoda
Journal of musculoskeletal & neuronal interactions, 23, 4, 407, 416, 2023年12月01日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The purpose of this study was to examine longitudinal growth changes in physical characteristics, muscle-tendon structure properties, and skeletal age in preadolescent boys and to compare the relationship between the changes in physical characteristics and muscle-tendon properties and the changes in chronological and skeletal ages. METHODS: Fourteen prepubescent boys (10.9 ± 1.1 years old at the onset of the study) participated in this study over two years (yearly). Maximal muscle strength and maximal strain of tendon structure during ramp isometric contraction and muscle and tendon thickness for knee extensors and plantar flexors were measured. In addition, skeletal age was assessed using Tanner-Whitehouse three method. RESULTS: Changes in height, thigh length, and lower leg length were highly correlated with changes in skeletal age but not chronological age. However, changes in the morphological and mechanical properties of muscle and tendon structure were not significantly associated with changes in chronological and skeletal ages. CONCLUSION: The present preliminary results suggest that longitudinal growth changes in the long-axis of the body are highly correlated with skeletal age change, whereas those in the muscle-tendon structure properties were not.

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

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, 2023年11月28日, ［国際誌］
英語, 研究論文（学術雑誌）, 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).

Association of wastewater SARS-CoV-2 load with confirmed COVID-19 cases at a university hospital in Sapporo, Japan during the period from February 2021 to February 2023.
Keisuke Kagami, Masaaki Kitajima, Hisashi Takahashi, Takanori Teshima, Nobuhisa Ishiguro
The Science of the total environment, 899, 165457, 165457, 2023年11月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been used to monitor trends in SARS-CoV-2 prevalence in a community without being influenced by clinical testing resources or healthcare-seeking behaviors. Since the rate of mortality from COVID-19 is higher in elderly patients with comorbidities, it is important to protect hospitalized patients from nosocomial infections caused by SARS-CoV-2. SARS-CoV-2 dissemination within a hospital ward was mostly mediated by healthcare workers (HCWs) and patients. HCWs need to understand the occurrence of COVID-19 and reflect this in their infection control measures. The aim of the present study was to determine the potential of SARS-CoV-2 RNA in wastewater as a leading indicator of confirmed COVID-19 cases at a university hospital. The trend of the geometric mean RNA concentrations in wastewater collected in Sapporo corresponded well with that of the number of newly confirmed COVID-19 cases at Hokkaido University Hospital between February 15, 2021 and February 26, 2023 (Pearson's r = 0.8823, p < 0.0001). Our results showed that monitoring SARS-CoV-2 RNA in municipal wastewater was useful for estimating the number of COVID-19 patients in healthcare facilities in the city.

High-precision rapid testing of omicron SARS-CoV-2 variants in clinical samples using AI-nanopore.
Kaoru Murakami, Shimpei I Kubota, Kumiko Tanaka, Hiroki Tanaka, Keiichiroh Akabane, Rigel Suzuki, Yuta Shinohara, Hiroyasu Takei, Shigeru Hashimoto, Yuki Tanaka, Shintaro Hojyo, Osamu Sakamoto, Norihiko Naono, Takayui Takaai, Kazuki Sato, Yuichi Kojima, Toshiyuki Harada, Takeshi Hattori, Satoshi Fuke, Isao Yokota, Satoshi Konno, Takashi Washio, Takasuke Fukuhara, Takanori Teshima, Masateru Taniguchi, Masaaki Murakami
Lab on a chip, 23, 22, 4909, 4918, 2023年11月07日, ［国際誌］
英語, 研究論文（学術雑誌）, A digital platform that can rapidly and accurately diagnose pathogenic viral variants, including SARS-CoV-2, will minimize pandemics, public anxiety, and economic losses. We recently reported an artificial intelligence (AI)-nanopore platform that enables testing for Wuhan SARS-CoV-2 with high sensitivity and specificity within five minutes. However, which parts of the virus are recognized by the platform are unknown. Similarly, whether the platform can detect SARS-CoV-2 variants or the presence of the virus in clinical samples needs further study. Here, we demonstrated the platform can distinguish SARS-CoV-2 variants. Further, it identified mutated Wuhan SARS-CoV-2 expressing spike proteins of the delta and omicron variants, indicating it discriminates spike proteins. Finally, we used the platform to identify omicron variants with a sensitivity and specificity of 100% and 94%, respectively, in saliva specimens from COVID-19 patients. Thus, our results demonstrate the AI-nanopore platform is an effective diagnostic tool for SARS-CoV-2 variants.

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, 2023年11月
日本語

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, 2023年11月
日本語

2022年度HIV-1薬剤耐性検査外部精度評価の報告　　　　　　　　　　　　　　　
吉田 繁, 松田 昌和, 今橋 真弓, 岡田 清美, 齊藤 浩一, 林田 庸総, 佐藤 かおり, 藤澤 真一, 遠藤 知之, 西澤 雅子, 椎野 禎一郎, 潟永 博之, 豊嶋 崇徳, 杉浦 亙, 吉村 和久, 菊地 正
日本エイズ学会誌, 25, 4, 443, 443, (一社)日本エイズ学会, 2023年11月
日本語

2022年の国内新規診断未治療HIV感染者・AIDS患者における薬剤耐性HIV1の動向　　　　　　　　　　　　　　　
菊地 正, 西澤 雅子, 小島 潮子, 大谷 眞智子, Runtwene Lucky, 椎野 禎一郎, 豊嶋 崇徳, 伊藤 俊広, 林田 庸総, 潟永 博之, 岡 慎一, 古賀 道子, 長島 真美, 貞升 健志, 佐野 貴子, 近藤 真規子, 宇野 俊介, 谷口 俊文, 猪狩 英俊, 寒川 整, 中島 秀明
日本エイズ学会誌, 25, 4, 444, 444, (一社)日本エイズ学会, 2023年11月
日本語

2022年度HIV-1薬剤耐性検査外部精度評価の報告　　　　　　　　　　　　　　　
吉田 繁, 松田 昌和, 今橋 真弓, 岡田 清美, 齊藤 浩一, 林田 庸総, 佐藤 かおり, 藤澤 真一, 遠藤 知之, 西澤 雅子, 椎野 禎一郎, 潟永 博之, 豊嶋 崇徳, 杉浦 亙, 吉村 和久, 菊地 正
日本エイズ学会誌, 25, 4, 443, 443, (一社)日本エイズ学会, 2023年11月
日本語

2022年の国内新規診断未治療HIV感染者・AIDS患者における薬剤耐性HIV1の動向　　　　　　　　　　　　　　　
菊地 正, 西澤 雅子, 小島 潮子, 大谷 眞智子, Runtwene Lucky, 椎野 禎一郎, 豊嶋 崇徳, 伊藤 俊広, 林田 庸総, 潟永 博之, 岡 慎一, 古賀 道子, 長島 真美, 貞升 健志, 佐野 貴子, 近藤 真規子, 宇野 俊介, 谷口 俊文, 猪狩 英俊, 寒川 整, 中島 秀明
日本エイズ学会誌, 25, 4, 444, 444, (一社)日本エイズ学会, 2023年11月
日本語

Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study
Shunsuke Uno, Hiroyuki Gatanaga, Tsunefusa Hayashida, Mayumi Imahashi, Rumi Minami, Michiko Koga, Sei Samukawa, Dai Watanabe, Teruhisa Fujii, Masao Tateyama, Hideta Nakamura, Shuzo Matsushita, Yusuke Yoshino, Tomoyuki Endo, Masahide Horiba, Toshibumi Taniguchi, Hiroshi Moro, Hidetoshi Igari, Shigeru Yoshida, Takanori Teshima, Hideaki Nakajima, Masako Nishizawa, Yoshiyuki Yokomaku, Yasumasa Iwatani, Atsuko Hachiya, Shingo Kato, Naoki Hasegawa, Kazuhisa Yoshimura, Wataru Sugiura, Tadashi Kikuchi
Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2023年10月19日, ［査読有り］
研究論文（学術雑誌）, Abstract

Background

Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%–5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings.

Methods

A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (&lt;50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens.

Results

E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure.

Conclusions

The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

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

Prolonged shedding of viable SARS‐CoV‐2 in immunocompromised patients with haematological malignancies: A prospective study
Takaya Ichikawa, Tomokazu Tamura, Mutsumi Takahata, Takashi Ishio, Makoto Ibata, Ikumi Kasahara, Koichiro Minauchi, Satoshi Yamamoto, Takanori Teshima, Takasuke Fukuhara
British Journal of Haematology, 204, 3, 815, 820, Wiley, 2023年10月05日
研究論文（学術雑誌）, Summary

Prolonged SARS‐CoV‐2 infection in immunocompromised individuals has been scattered, but the details remain unclear. We conducted a prospective study with 26 COVID‐19 patients with haematological malignancies to determine viral shedding kinetics and characteristics. We obtained nasopharyngeal swabs from the patients 21–28 days post‐onset for a PCR test and performed virus isolation from the PCR‐positive samples. A viable virus was detected in five patients (19.2%), all of whom had malignant lymphoma. Those patients had significantly lower CD4⁺ T‐cell counts than the PCR‐negative patients. A comparison of previous chemotherapy showed that anti‐CD20 antibodies and bendamustine may be risk factors for prolonged viral shedding.

新規発症の急性リンパ性白血病におけるWT1　　　　　　　　　　　　　　　
松川 敏大, 小野澤 真弘, 長井 惇, 吉田 匠汰, 宮下 直樹, 木村 弘幸, 金谷 穣, 太田 秀一, 盛 暁生, 近藤 健, 柿木 康孝, 皆内 康一郎, 重松 明男, 若狭 健太郎, 橋口 淳一, 石原 敏道, 藤本 勝也, 堤 豊, 井端 淳, 酒井 基, 小宅 達郎, 豊嶋 崇徳
日本血液学会学術集会, 85回, 395, 395, (一社)日本血液学会, 2023年10月
英語

Dominant-negativeタイプのIKZF1欠失が成人B細胞性急性リンパ性白血病に与える影響　　　　　　　　　　　　　　　
木村 弘幸, 小野澤 真弘, 吉田 匠汰, 宮下 直樹, 松川 敏大, 平林 真介, 後藤 秀樹, 小栗 聡, 藤澤 真一, 盛 暁生, 近藤 健, 日高 大輔, 岡田 耕平, 太田 秀一, 柿木 康孝, 堤 豊, 山本 聡, 宮城島 拓人, 橋口 淳一, 永嶋 貴博, 井端 淳, 横山 翔大, 若狭 健太郎, 長谷山 美仁, 高橋 承吾, 藤本 勝也, 石原 敏道, 酒井 基, 豊嶋 崇徳
日本血液学会学術集会, 85回, 1095, 1095, (一社)日本血液学会, 2023年10月
英語

NPM1変異陽性急性骨髄性白血病におけるDNMT3A R882変異の臨床的意義　　　　　　　　　　　　　　　
宮下 直樹, 小野澤 真弘, 吉田 匠汰, 長井 惇, 木村 弘幸, 横山 翔大, 松川 敏大, 杉田 純一, 小笠原 励起, 日高 大輔, 盛 暁生, 近藤 健, 松岡 里湖, 重松 明男, 若狭 健太郎, 笠原 郁美, 佐賀 智之, 橋口 淳一, 武田 紫, 井端 淳, 堤 豊, 藤本 勝也, 豊嶋 崇徳
日本血液学会学術集会, 85回, 1222, 1222, (一社)日本血液学会, 2023年10月
英語

Ultrasonographic diagnosis of cystitis glandularis with severe intestinal metaplasia.
Satomi Omotehara, Mutsumi Nishida, Momoka Kikuchi, Yusuke Kudo, Aya Matsui, Soshu Sato, Shin-Ichi Murata, Hiroko Gotoda, Takanori Teshima
Journal of clinical ultrasound : JCU, 51, 8, 1397, 1400, 2023年10月, ［国際誌］
英語, 研究論文（学術雑誌）, This study presents the case of man who underwent ultrasonography (US) for the diagnosis and follow-up of cystitis glandularis with severe intestinal metaplasia. We believe that our study makes a significant contribution to the literature because the findings of cystitis glandularis that forms a mass is relatively rare.

悪性リンパ腫へのtisagenlecleucelの治療効果に関するPET/CTで評価されたMTHとDmaxのインパクト　　　　　　　　　　　　　　　
後藤 秀樹, 北脇 年雄, 加藤 光次, 藤井 伸治, 大西 康, 福原 規子, 山内 拓司, 虎谷 和則, 下茂 雅俊, 小林 宏紀, 小野寺 晃一, 吉田 匠汰, 千丈 創, 小野澤 真弘, 平田 健司, 横田 勲, 豊嶋 崇徳
日本血液学会学術集会, 85回, 1193, 1193, (一社)日本血液学会, 2023年10月
英語

臨床症状および抗核抗体パターンと矛盾した各種自己抗体陽性を認めた1症例
菊地 菜海, 山下 直樹, 安田 慶子, 後藤 秀樹, 豊嶋 崇徳
北臨技会誌, 21, 2, 71, 76, (一社)北海道臨床衛生検査技師会, 2023年10月
日本語

Prognostic Value of Hematogones in Patients With Hematopoietic Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.
Hirotaka Mori, Daisuke Koyama, Yuki Sato, Yuki Kataoka, Shunsuke Taito, Takashi Ishio, Takanori Teshima, Isao Yokota
Cureus, 15, 10, e47184, 2023年10月, ［国際誌］
英語, 研究論文（学術雑誌）, This systematic review and meta-analysis aimed to determine whether hematogones in patients with hematopoietic disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with clinical outcomes. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases from their inception to March 2023. The primary outcome in the summary of findings was three-year relapse-free survival (RFS), and secondary outcomes in the summary of findings included three-year relapse, non-relapse mortality (NRM), overall survival (OS), acute and chronic graft-versus-host disease (GVHD), and infection. The certainty of evidence was determined using the grading of recommendation assessment, development, and evaluation approaches. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. This study protocol was registered in the Open Science Framework. A total of six studies (including 888 patients) were included in the meta-analysis. Hematogones were related to favorable three-year RFS (risk ratio (RR) = 1.84; 95% confidence interval (CI) = 1.01 to 3.34) and favorable NRM (RR = 0.14; 95% CI = 0.04 to 0.51), OS (RR = 1.51; 95% CI = 1.13 to 2.02), and acute GVHD (RR = 0.44; 95% CI = 0.33 to 0.59). The certainty of the evidence was low for RFS, NRM, OS, and acute GVHD. Evidence regarding the association between hematogones, relapse, and infections is uncertain. Hematogones may be a prognostic factor for long-term prognosis and acute adverse events in patients with hematopoietic disorders after allo-HSCT. Further studies are required to address the long-term life-threatening events.

Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD.
Nataliya P Buxbaum, Gerard Socié, Geoffrey R Hill, Kelli P A MacDonald, Victor Tkachev, Takanori Teshima, Stephanie J Lee, Jerome Ritz, Stefanie Sarantopoulos, Leo Luznik, Defu Zeng, Sophie Paczesny, Paul J Martin, Steven Z Pavletic, Kirk R Schultz, Bruce R Blazar
Blood advances, 7, 17, 4886, 4902, 2023年09月12日, ［国際誌］
英語, 研究論文（学術雑誌）, Chronic graft-versus-host disease (cGvHD) remains a prominent barrier to allogeneic hematopoietic stem cell transplantion as the leading cause of nonrelapse mortality and significant morbidity. Tremendous progress has been achieved in both the understanding of pathophysiology and the development of new therapies for cGvHD. Although our field has historically approached treatment from an empiric position, research performed at the bedside and bench has elucidated some of the complex pathophysiology of cGvHD. From the clinical perspective, there is significant variability of disease manifestations between individual patients, pointing to diverse biological underpinnings. Capitalizing on progress made to date, the field is now focused on establishing personalized approaches to treatment. The intent of this article is to concisely review recent knowledge gained and formulate a path toward patient-specific cGvHD therapy.

Incidence and course of Epstein-Barr virus viremia after allogeneic hematopoietic stem cell transplant for adult-onset systemic chronic active Epstein-Barr virus disease.
Preeti Prerna M Vaswani, Masahiro Onozawa, Yuta Hasegawa, Hiroyuki Ohigashi, Takahide Ara, Toshihiro Matsukawa, Atsushi Yasumoto, Souichi Shiratori, Hideki Goto, Masao Nakagawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
Bone marrow transplantation, 2023年09月05日, ［国際誌］
英語

Factors associated with household transmission of SARS-CoV-2 omicron variant to health care workers: A retrospective cohort study.
Keisuke Kagami, Reiko Oyamada, Tsubasa Watanabe, Sho Nakakubo, Takahiro Hayashi, Sumio Iwasaki, Tatsuya Fukumoto, Takayuki Usami, Kasumi Hayasaka, Shinichi Fujisawa, Chiaki Watanabe, Mutsumi Nishida, Takanori Teshima, Yusuke Niinuma, Isao Yokota, Yoh Takekuma, Mitsuru Sugawara, Nobuhisa Ishiguro
International journal of nursing practice, 29, 5, e13195, 2023年08月24日, ［国際誌］
英語, 研究論文（学術雑誌）, AIM: The aim of this study was to determine the risk factors for household transmission of the omicron variant of SARS-CoV-2. BACKGROUND: The household infection rate has been reported to be higher for the omicron variant than for non-omicron variants of SARS-CoV-2. Determination of the risk factors for household transmission of the omicron variant is therefore important. DESIGN: A Retrospective Cohort Study was conducted. METHODS: When family members of health care workers (HCWs) were found to be infected with SARS-CoV-2, the HCWs had to receive two nucleic acid amplification tests for SARS-CoV-2: immediately after and 5 to 10 days after the onset of COVID-19 in the family members. Risk factors of household transmission were analysed by comparing cases (HCWs infected with SARS-CoV-2) and controls (HCWs not infected with SARS-CoV-2) using multivariable analysis. RESULTS: Unvaccinated status (OR: 3.97), age of index cases (≤6 years) (OR: 1.94) and staying at home with index cases (OR: 10.18) were risk factors for household transmission. CONCLUSION: If there is a strong desire to avoid household infection, family members infected with SARS-CoV-2 should live separately during the period of viral shedding.

Dominant-negative type of IKZF1 deletion showed a favorable prognosis in adult B-cell acute lymphoblastic leukemia.
Hiroyuki Kimura, Masahiro Onozawa, Shota Yoshida, Naoki Miyashita, Shota Yokoyama, Toshihiro Matsukawa, Shinsuke Hirabayashi, Hideki Goto, Tomoyuki Endo, Satoshi Oguri, Shinichi Fujisawa, Akio Mori, Takeshi Kondo, Daisuke Hidaka, Kohei Okada, Shuichi Ota, Yasutaka Kakinoki, Yutaka Tsutsumi, Satoshi Yamamoto, Takuto Miyagishima, Junichi Hashiguchi, Takahiro Nagashima, Makoto Ibata, Kentaro Wakasa, Yoshihito Haseyama, Katsuya Fujimoto, Toshimichi Ishihara, Hajime Sakai, Takanori Teshima
Annals of hematology, 2023年08月19日, ［国際誌］
英語, 研究論文（学術雑誌）, IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function (LOF) deletions. The prognostic impact of each deletion has not been fully elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion and multiplex PCR for the 4 most common IKZF1 deletions (∆4-7, ∆2-7, ∆2-8, and ∆4-8). Samples, in which IKZF1 deletion was detected by FISH but a specific type of deletion was not identified by the PCR, were categorized as "other." Patients were classified into a DN group that had at least 1 allele of ∆4-7 (n = 23), LOF and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative cases. LOF and other type IKZF1 deletions were found in 43.4% of BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the DN group showed significantly higher overall survival (OS) than that of the LOF and other and WT groups (P = 0.011). Multivariate analysis including age, WBC counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age ≥ 65 (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients.Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015-0344).

Booster effect of a third mRNA-based COVID-19 vaccine dose in patients with myeloid malignancies.
Akio Mori, Masahiro Onozawa, Mirei Kobayashi, Shihori Tsukamoto, Hajime Senjo, Takashi Ishio, Emi Yokoyama, Minoru Kanaya, Koh Izumiyama, Makoto Saito, Haruna Muraki, Masanobu Morioka, Takanori Teshima, Takeshi Kondo
Cancer medicine, 12, 16, 16881, 16888, 2023年08月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: We have reported that seroconversion rates after the second dose of mRNA-based COVID-19 vaccines for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) were 100% and 95% respectively, with no significant difference from healthy controls (HCs).However, there are very limited data for the response to a third vaccine dose in those patients. AIMS: In this complementary study, we investigated the booster effect of a third mRNA-based COVID-19 vaccine dose in patients with myeloid malignancies. MATERIALS & METHODS: A total 58 patients including 20 patients with MDS and 38 patients with AML were enrolled. Anti-SARS-CoV-2S immunoassays were performed at 3, 6, and 9 months after the second vaccine dose. RESULTS: Seventy-five percent of the MDS patients and 37% of the AML patients were receiving active treatment at the time of the third vaccination. Both the initial and third vaccine response in AML patients were comparable to those in HCs. In MDS patients, although the initial vaccine immunogenicity was inferior to that in HCs and AML patients, the third vaccine improved the response to a level not inferior to those in HCs and AML patients. Of note, the third vaccine resulted in a significant increase of antibodies in actively treated MDS patients who had shown a response inferior to that in untreated patients after two doses of vaccination. DISCUSSION: In patients with myeloid malignancies, the third vaccine dose showed a booster effect, and disease- and therapy-related factors associated with the booster response have been identified. CONCLUSION: The third dose of an mRNA-based COVID-19 vaccine showed a booster effect in patients with myeloid malignancies. Such a good booster response has not been reported in other haematological malignancies.

抗トロポニンI抗体vs.抗トロポニンT抗体の存在様式と出現頻度
中野 恵一, 村上 聡, 清宮 正徳, 安田 慶子, 山下 直樹, 後藤 秀樹, 豊嶋 崇徳
医療検査と自動化, 48, 4, 386, 386, (一社)日本医療検査科学会, 2023年08月
日本語

抗トロポニンI抗体vs.抗トロポニンT抗体の存在様式と出現頻度　　　　　　　　　　　　　　　
中野 恵一, 村上 聡, 清宮 正徳, 安田 慶子, 山下 直樹, 後藤 秀樹, 豊嶋 崇徳
医療検査と自動化, 48, 4, 386, 386, (一社)日本医療検査科学会, 2023年08月
日本語

Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3-ITD positive AML.
Toru Miyajima, Masahiro Onozawa, Shota Yoshida, Naoki Miyashita, Hiroyuki Kimura, Shogo Takahashi, Shota Yokoyama, Toshihiro Matsukawa, Hideki Goto, Junichi Sugita, Shinichi Fujisawa, Daisuke Hidaka, Reiki Ogasawara, Akio Mori, Satomi Matsuoka, Akio Shigematsu, Kentaro Wakasa, Ikumi Kasahara, Tomoyuki Saga, Junichi Hashiguchi, Yukari Takeda, Makoto Ibata, Tsutsumi Yutaka, Katsuya Fujimoto, Takeshi Kondo, Takanori Teshima
European journal of haematology, 2023年07月19日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The cryptic fusion oncogene NUP98::NSD1 is known to be associated with FLT3-ITD mutation in acute myeloid leukemia (AML), and an independent poor prognostic factor in pediatric AML. However, there are little data regarding the clinical significance of NUP98::NSD1 in adult cohort. METHODS: We conducted a multicenter retrospective study to investigate the prevalence, clinical characteristics, and prognostic impact of NUP98::NSD1 in adult FLT3-ITD-positive AML patients. RESULTS: In a total of 97 FLT3-ITD-positive AML patients, six cases (6.2%) were found to harbor the NUP98::NSD1 fusion transcript. NUP98::NSD1 positive cases had significantly higher platelet counts and a higher frequency of FAB-M4 morphology than NUP98::NSD1 negative cases. NUP98::NSD1 was found to be mutually exclusive with NPM1 mutation, and was accompanied by the WT1 mutation in three of the six cases. The presence of NUP98::NSD1 fusion at the time of diagnosis predicted poor response to cytarabine-anthracycline-based intensive induction chemotherapy (induction failure rate: 83% vs. 36%, p = .038). Five of the six cases with NUP98::NSD1 underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two of the five cases have successfully maintained remission, with one of them being rescued through a second HSCT. CONCLUSIONS: Detecting NUP98::NSD1 in adult FLT3-ITD-positive AML is crucial to recognizing chemotherapy-resistant group.

Assessment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome using different scanning approaches for the ultrasonographic evaluation of portal vein blood flow and hepatic artery resistive index in hematopoietic stem cell transplant recipients.
Momoka Kikuchi, Takahito Iwai, Mutsumi Nishida, Yusuke Kudo, Satomi Omotehara, Megumi Sato, Junichi Sugita, Hideki Goto, Isao Yokota, Takanori Teshima
Journal of medical ultrasonics (2001), 2023年07月04日, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Previously, we established a scoring system (Hokkaido ultrasound-based scoring system-10; HokUS-10) comprising 10 ultrasound parameters for SOS diagnosis. In HokUS-10, the portal vein time-averaged flow velocity (PV TAV) and hepatic artery resistive index (HA RI) are measured using subcostal scanning. However, measurement errors and delineation difficulties occur. Therefore, we aimed to prospectively evaluate PV TAV and HA RI measurements obtained via intercostal scanning as an alternative method to subcostal scanning and determine their cutoff values. METHODS: HokUS-10 was administered before and after HSCT. PV TAV and HA RI were measured on subcostal and right intercostal scans. RESULTS: We performed 366 scans on 74 patients. The median value (range) of PV TAV in the main and right portal veins was 15.0 cm/s (2.2-49.6 cm/s) and 10.5 cm/s (1.6-22.0 cm/s), respectively. A low correlation was observed between the two values (r = 0.39, p < 0.01). The highest diagnostic value of the right portal vein was less than 8.0 cm/s. The median value (range) of HA RI in the proper and right hepatic arteries was 0.72 (0.52-1.00) and 0.70 (0.51-1.00), respectively. A strong correlation was observed between the two values (r = 0.65, p < 0.01). The highest diagnostic value of the right HA RI was 0.72 or higher. CONCLUSION: Quantitative measurement of PV TAV and HA RI using intercostal scanning can be appropriately performed as an alternative method to using subcostal scanning.

Corrigendum to "IgG4-IgE complex in patients with IgG4-related disease" [Clin. Chim. Acta 531 (2022) 261-264].
Keiichi Nakano, Junichi Sugita, Masanori Seimiya, Keiko Yasuda, Chiaki Watanabe, Takanori Teshima
Clinica chimica acta; international journal of clinical chemistry, 547, 117454, 117454, 2023年07月01日, ［国際誌］
英語

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

Novel insights into GVHD and immune reconstitution after allogeneic hematopoietic cell transplantation.
Takanori Teshima, Jaap Jan Boelens, Ken-Ichi Matsuoka
Blood cell therapy, 6, 2, 42, 48, 2023年05月25日, ［国内誌］
英語, 研究論文（学術雑誌）, Effective control of the graft-versus-host disease (GVHD) and immune reconstitution are crucial in improving the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) as well as the quality of life of the transplant survivors. Recent basic and clinical studies have deepened our understanding of the mechanisms of the immunological sequelae of HSCT, GVHD, and compromised immune systems. Based on the findings, various novel approaches have also been developed and tested clinically. However, further studies are necessary to develop therapeutic strategies with significant clinical benefits.

Association of demographics, HCV co‐infection, HIV‐1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV‐1 Surveillance Network
Machiko Otani, Teiichiro Shiino, Atsuko Hachiya, Hiroyuki Gatanaga, Dai Watanabe, Rumi Minami, Masako Nishizawa, Takanori Teshima, Shigeru Yoshida, Toshihiro Ito, Tsunefusa Hayashida, Michiko Koga, Mami Nagashima, Kenji Sadamasu, Makiko Kondo, Shingo Kato, Shunsuke Uno, Toshibumi Taniguchi, Hidetoshi Igari, Sei Samukawa, Hideaki Nakajima, Yusuke Yoshino, Masahide Horiba, Hiroshi Moro, Tamayo Watanabe, Mayumi Imahashi, Yoshiyuki Yokomaku, Haruyo Mori, Teruhisa Fujii, Kiyonori Takada, Asako Nakamura, Hideta Nakamura, Masao Tateyama, Shuzo Matsushita, Kazuhisa Yoshimura, Wataru Sugiura, Tetsuro Matano, Tadashi Kikuchi
Journal of the International AIDS Society, 26, 5, Wiley, 2023年05月23日, ［査読有り］
研究論文（学術雑誌）

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 Journal, American Society of Hematology, 2023年05月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis is standard in allogeneic hematopoietic stem cell transplantation (HCT) but fails to induce long-term tolerance without chronic GVHD in a considerable number of patients. In this study, we addressed this long-standing question in mouse models of HCT. After HCT, alloreactive donor T cells rapidly differentiated into PD-1+ TIGIT+ terminally exhausted T cells (terminal-Tex). GVHD prophylaxis with cyclosporine (CSP) suppressed donor T-cell expression of TOX, a master regulator to promote differentiation of transitory exhausted T cells (transitory-Tex), expressing both inhibitory receptors and effector molecules, into terminal-Tex, and inhibited tolerance induction. Adoptive transfer of transitory-Tex, but not terminal-Tex, into secondary recipients developed chronic GVHD. Transitory-Tex maintained alloreactivity and thus PD-1 blockade restored graft-versus-leukemia (GVL) activity of transitory-Tex, not terminal-Tex. In conclusion, CSP inhibits tolerance induction by suppressing the terminal exhaustion of donor T cells, while maintaining GVL effects to suppress leukemia relapse.

Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection
Yutaka Tsutsumi, Shinichi Ito, Souichi Shiratori, Takanori Teshima
Cancers, 15, 10, 2852, 2852, MDPI AG, 2023年05月21日, ［査読有り］, ［最終著者］
研究論文（学術雑誌）, The hepatitis C virus (HCV) is potentially associated with liver cancer, and advances in various drugs have led to progress in the treatment of hepatitis C and attempts to prevent its transition to liver cancer. Furthermore, reactivation of HCV has been observed in the treatment of lymphoma, during which the immortalization and proliferation of lymphocytes occur, which leads to the possibility of further stimulating cytokines and the like and possibly to the development of lymphoid malignancy. There are also cases in which the disappearance of lymphoid malignancy has been observed by treating HCV and suppressing HCV-Ribonucleic acid (RNA), as well as cases of recurrence with an increase in HCV-RNA. While HCV-associated lymphoma has a poor prognosis, improving the prognosis with Direct Acting Antivirals (DAA) has recently been reported. The reduction and eradication of HCV-RNA by means of DAA is thus important for the treatment of lymphoid malignancy associated with HCV infection, and HCV-RNA can presumably play a role as a biomarker. This review provides an overview of what is currently known about HCV-associated lymphoma, its epidemiology, the mechanisms underlying the progression to lymphoma, its treatment, the potential and limits of HCV-RNA as a therapeutic biomarker, and biomarkers that are expected now that DAA therapy has been developed.

Pseudotumor of the skin due to Mycobacterium genavense.
Suguru Kurosawa, Keisuke Imafuku, Sho Nakakubo, Sumio Iwasaki, Takanori Teshima, Hideki Goto, Hideyuki Ujiie
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2023年05月15日, ［国際誌］
英語, Mycobacterium genavense is a rare type of non-tuberculous mycobacterium (NTM) that has been reported to cause disseminated infections in immunocompromised patients. Because M. genavense is slow-growing and poorly able to form colonies on Ogawa's medium, genetic and molecular analyses are necessary to identify this pathogen. NTM infections present with various cutaneous manifestations. Of these, rare cases have been reported to present with mycobacterial pseudotumors. However, there are no reports of M. genavense with cutaneous pseudotumors. In this paper, we report a case of a pseudotumor due to M. genavense infection that was observed only in a cutaneous lesion. The patient was taking 5 mg of prednisolone and was aware of a tumor on the right lower leg. Biopsy samples showed diffuse spindle-shaped histiocytes and various other inflammatory cell infiltrates, and Ziehl-Neelsen staining detected mycobacterium. Since no colonies formed on Ogawa medium, genetic testing was performed, and M. genavense was identified by DNA sequence analysis. There were no other disseminated lesions beyond the skin, including in the lungs and liver. Since the patient was immunosuppressed, in accordance with previous literature, a combination therapy of clarithromycin, ethambutol, and rifampicin for 4 months was recommended. When no growth is observed on Ogawa's medium in cases of infection, it is essential to identify the infectious pathogen by genetic analysis.

Mycobacterium genavenseによる限局性の皮膚感染症を呈した1例　　　　　　　　　　　　　　　
黒澤 卓, 今福 恵輔, 宮澤 元, 中久保 祥, 岩崎 澄央, 後藤 秀樹, 豊嶋 崇徳, 氏家 英之
日本臨床皮膚科医会雑誌, 40, 3, 470, 470, 日本臨床皮膚科医会, 2023年05月
日本語

Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial
Stephan A Grupp, Selim Corbacioglu, Hyoung Jin Kang, Takanori Teshima, Seong Lin Khaw, Franco Locatelli, Johan Maertens, Matthias Stelljes, Polina Stepensky, Paty Lopez, Vian Amber, Antonio Pagliuca, Paul G Richardson, Mohamad Mohty
The Lancet Haematology, 10, 5, e333, e345, Elsevier BV, 2023年05月, ［査読有り］
研究論文（学術雑誌）

Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan
Hideki Goto, Toshio Kitawaki, Nobuharu Fujii, Koji Kato, Yasushi Onishi, Noriko Fukuhara, Takuji Yamauchi, Kazunori Toratani, Hiroki Kobayashi, Shota Yoshida, Masatoshi Shimo, Koichi Onodera, Hajime Senjo, Masahiro Onozawa, Kenji Hirata, Isao Yokota, Takanori Teshima
International Journal of Clinical Oncology, 28, 6, 816, 826, Springer Science and Business Media LLC, 2023年04月18日, ［査読有り］, ［最終著者］, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Tisagenlecleucel, an autologous CD19-directed T-cell immunotherapy, can induce a durable response in adult patients with relapsed/refractory (r/r) B-cell lymphoma. METHODS: To elucidate the outcome of chimeric antigen receptor (CAR) T-cell therapy in Japanese, we retrospectively analyzed the outcomes of 89 patients who received tisagenlecleucel for r/r diffuse large B-cell lymphoma (n = 71) or transformed follicular lymphoma (n = 18). RESULTS: With a median follow-up of 6.6-months, 65 (73.0%) patients achieved a clinical response. The overall survival (OS) and event-free survival (EFS) rates at 12 months were 67.0% and 46.3%, respectively. Overall, 80 patients (89.9%) had cytokine release syndrome (CRS), and 6 patients (6.7%) had a grade ≥ 3 event. ICANS occurred in 5 patients (5.6%); only 1 patient had grade 4 ICANS. Representative infectious events of any grade were cytomegalovirus viremia, bacteremia and sepsis. The most common other adverse events were ALT elevation, AST elevation, diarrhea, edema, and creatinine elevation. No treatment-related mortality was observed. A Sub-analysis showed that a high metabolic tumor volume (MTV; ≥ 80 ml) and stable disease /progressive disease before tisagenlecleucel infusion were both significantly associated with a poor EFS and OS in a multivariate analysis (P < 0.05). Notably, the combination of these 2 factors efficiently stratified the prognosis of these patients (HR 6.87 [95% CI 2.4-19.65; P < 0.05] into a high-risk group). CONCLUSION: We report the first real-world data on tisagenlecleucel for r/r B-cell lymphoma in Japan. Tisagenlecleucel is feasible and effective, even in late line treatment. In addition, our results support a new algorithm for predicting the outcomes of tisagenlecleucel.

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

Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study
David Bernard Miklos, Mohammad Abu Zaid, Julian P. Cooney, Jörn C. Albring, Mary Flowers, Alan P. Skarbnik, Ibrahim Yakoub-Agha, Bor-Sheng Ko, Benedetto Bruno, Edmund K. Waller, Jean Yared, Sang Kyun Sohn, Claude-Eric Bulabois, Takanori Teshima, David Jacobsohn, Hildegard Greinix, Ahmad Mokatrin, Yihua Lee, Justin T. Wahlstrom, Lori Styles, Gerard Socie
Journal of Clinical Oncology, 41, 10, 1876, 1887, American Society of Clinical Oncology (ASCO), 2023年04月01日, ［査読有り］
研究論文（学術雑誌）, PURPOSE

To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD).

METHODS

Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety.

RESULTS

Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients.

CONCLUSION

There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.

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

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

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

Humoral response to mRNA-based COVID-19 vaccine and booster effect of a third dose in patients with mature T cell and NK-cell neoplasms
Mirei Kobayashi, Akio Mori, Masahiro Onozawa, Shihori Tsukamoto, Hajime Senjo, Takashi Ishio, Emi Yokoyama, Minoru Kanaya, Koh Izumiyama, Makoto Saito, Haruna Muraki, Masanobu Morioka, Takanori Teshima, Takeshi Kondo
Annals of Hematology, 102, 4, 819, 827, Springer Science and Business Media LLC, 2023年03月02日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Abstract

Patients with lymphoid malignancies have impaired humoral immunity caused by the disease itself and its treatment, placing them at risk for severe coronavirus disease-19 (COVID-19) and reduced response to vaccination. However, data for COVID-19 vaccine responses in patients with mature T cell and NK-cell neoplasms are very limited. In this study of 19 patients with mature T/NK-cell neoplasms, anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike antibodies were measured at 3 months, 6 months, and 9 months after the second mRNA-based vaccination. At the time of the second and third vaccinations, 31.6% and 15.4% of the patients were receiving active treatment. All patients received the primary vaccine dose and the third vaccination rate was 68.4%. In patients with mature T/NK-cell neoplasms, both seroconversion rate (p < 0.01) and antibody titers (p < 0.01) after the second vaccination were significantly lower than those in healthy controls (HC). In individuals who received the booster dose, patients had significantly lower antibody titers than those in HC (p < 0.01); however, the seroconversion rate in patients was 100%, which was the same as that in HC. The booster vaccine resulted in a significant increase of antibodies in elderly patients who had shown a response that was inferior to that in younger patients after two doses of vaccination. Since higher antibody titers and higher seroconversion rate reduced the incidence of infection and mortality, vaccination more than three times may have the advantage for patients with mature T/NK-cell neoplasms, especially in elderly patients. Clinical trial registration number: UMIN 000,045,267 (August 26th, 2021), 000,048,764 (August 26th, 2022).

Correction to: Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.
Mutsumi Nishida, Junichi Sugita, Shuichiro Takahashi, Takahito Iwai, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Ryosuke Sakano, Hitoshi Shibuya, Isao Yokota, Akihiro Iguchi, Takanori Teshima
International journal of hematology, 117, 3, 468, 468, 2023年03月, ［国内誌］
英語

Prognostic impact of FLT3-ITD, NPM1 mutation and CEBPA bZIP domain mutation in cytogenetically normal acute myeloid leukemia: a Hokkaido Leukemia Net study
Naoki Miyashita, Masahiro Onozawa, Shota Yoshida, Hiroyuki Kimura, Shogo Takahashi, Shota Yokoyama, Toshihiro Matsukawa, Shinsuke Hirabayashi, Shinichi Fujisawa, Akio Mori, Shuichi Ota, Yasutaka Kakinoki, Yutaka Tsutsumi, Satoshi Yamamoto, Takuto Miyagishima, Takahiro Nagashima, Makoto Ibata, Kentaro Wakasa, Yoshihito Haseyama, Katsuya Fujimoto, Toshimichi Ishihara, Hajime Sakai, Takeshi Kondo, Takanori Teshima
International Journal of Hematology, 118, 1, 36, 46, Springer Science and Business Media LLC, 2023年02月28日, ［査読有り］, ［最終著者］, ［国内誌］
英語, 研究論文（学術雑誌）, Mutation status of FLT3, NPM1, and CEBPA is used to classify the prognosis of acute myeloid leukemia, but its significance in patients with cytogenetically normal (CN) AML is unclear. We prospectively analyzed these genes in 295 patients with CN-AML and identified 76 (25.8%) FLT3-ITD, 113 (38.3%) NPM1 mutations, and 30 (10.2%) CEBPA biallelic mutations. We found that patients with FLT3-ITD had a poor prognosis at any age, while patients with CEBPA biallelic mutation were younger and had a better prognosis. FLT3-ITD and NPM1 mutations were correlated, and the favorable prognostic impact of being FLT3-ITD negative and NPM1 mutation positive was evident only in patients aged 65 years or more. For CEBPA, 86.7% of the patients with biallelic mutation and 9.1% of patients with the single allele mutation had in-frame mutations in the bZIP domain, which were strongly associated with a favorable prognosis. Multivariate analysis showed that age < 65 years, FLT3-ITD and CEBPA bZIP in-frame mutation were independent prognostic factors. The results suggest that analyzing these gene mutations at diagnosis can inform selection of the optimal intensity of therapy for patients with CN-AML.

IgG4-IgE複合体の保有頻度とIgE、IgG4濃度の比較に関する研究
中野 恵一, 安田 慶子, 清宮 正徳, 渡邊 千秋, 後藤 秀樹, 豊嶋 崇徳
生物試料分析, 46, 1, 51, 51, (NPO)生物試料分析科学会, 2023年02月
日本語

IgG4-IgE complex interferes with measurement of IgE concentration
Keiichi Nakano, Junichi Sugita, Masanori Seimiya, Keiko Yasuda, Chiaki Watanabe, Hideki Goto, Takanori Teshima
Clinical Biochemistry, 112, 11, 16, Elsevier BV, 2023年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND AND AIMS: Patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) have elevated immunoglobulin E (IgE) concentration compared to that in healthy individuals, which suggests the occurrence of IgE-mediated allergic reactions. We have previously shown that IgG4 and IgE form a complex in some patients with IgG4-RD. However, it is currently unknown whether and how the presence of the IgG4-IgE complex affects IgE concentration measurements by different assays. MATERIALS AND METHODS: Twenty patients with confirmed presence or absence of IgG4-IgE complex were evaluated. We compared IgE concentrations measured by ST AIA-PACK IgE II (AIA-PACK), Elecsys IgE II Immunoassay (Elecsys), and Iatroace IgE (Iatroace) and evaluated to what extent the IgG4-IgE complex interfered with these measurements. RESULTS: In patients with the IgG4-IgE complex, IgE concentrations measured using Iatroace were significantly lower than those measured using Elecsys and tended to be lower than those measured using AIA-PACK. IgE concentrations determined by Iatroace were significantly different in patients with and without the IgG4-IgE complex, whereas no significant differences between these groups were detected when IgE concentrations were measured by AIA-PACK or Elecsys. CONCLUSION: The formation of the IgG4-IgE complex underestimates measured IgE concentrations depending on the method used. Therefore, caution should be exercised when selecting a specific IgE assay for patients with IgG4-RD.

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

Mocravimod, a Selective Sphingosine-1-Phosphate Receptor Modulator, in Allogeneic Hematopoietic Stem Cell Transplantation for Malignancy.
Simone Dertschnig, Peter Gergely, Jürgen Finke, Urs Schanz, Ernst Holler, Udo Holtick, Gérard Socié, Michael Medinger, Jakob Passweg, Takanori Teshima, Christos Stylianou, Stephan Oehen, Dominik Heim, Christoph Bucher
Transplantation and cellular therapy, 29, 1, 41.e1-41.e9, 2023年01月, ［国際誌］
英語, 研究論文（学術雑誌）, Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option for patients with acute myelogenous leukemia. Outcomes are limited by leukemia relapse, graft-versus-host disease (GVHD), and abnormal immune reconstitution. Mocravimod (KRP203) is an oral sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lymphoid organs. Mocravimod retains T cell effector function, a main differentiator to immunosuppressants. In preclinical models, mocravimod improves survival by maintaining graft-versus-leukemia (GVL) activity while reducing GVHD. In patients undergoing allo-HSCT for hematological malignancies, mocravimod is postulated to prevent GVHD by redistributing allogeneic donor T cells to lymphoid tissues while allowing a sufficient GVL effect in the lymphoid, where malignant cells usually reside. The primary objective of this study was to assess the safety and tolerability of mocravimod in patients undergoing allo-HSCT for hematologic malignancies. Secondary objectives were to determine the pharmacokinetic profiles of mocravimod and its active metabolite mocravimod-phosphate in this patient group, as well as to assess GVHD-free, relapse free survival at 6 months after the last treatment. In this 2-part, single- and 2-arm randomized, open-label trial, we evaluated the safety, tolerability, and pharmacokinetics of mocravimod in allo-HSCT recipients (ClinicalTrials.gov identifier NCT01830010). Patients received either 1 mg or 3 mg mocravimod per day on top of standard of care GVHD prophylaxis with either cyclosporine A/methotrexate or tacrolimus/methotrexate. We found that mocravimod can be safely added to standard treatment regimens in patients with hematologic malignancies requiring allo-HSCT. Mocravimod resulted in a significant reduction of circulating lymphocyte numbers and had no negative impact on engraftment and transplantation outcomes. Our results indicate that mocravimod is safe and support a larger study to investigate its efficacy in a homogeneous acute myelogenous leukemia patient population undergoing allo-HSCT.

A case of breast angiosarcoma clearly delineated by contrast-enhanced ultrasonography.
Takahito Iwai, Mutsumi Nishida, Yusuke Kudo, Satomi Omotehara, Kenjiro Kato, Emi Takakuwa, Ai Shimizu, Fumi Kato, Mitsuchika Hosoda, Masato Takahashi, Takanori Teshima
Journal of clinical ultrasound : JCU, 51, 6, 1048, 1050, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, We present a case of breast angiosarcoma. Although B-mode ultrasonography did not indicate a tumor, contrast-enhanced ultrasonography (CEUS) was successfully delineated it. CEUS helped identify the tumor and its extent.

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

Breaking away from an endemic state of multidrug-resistant Pseudomonas aeruginosa by daily sink disinfection.
Sumio Iwasaki, Rikako Sato, Keisuke Kagami, Kouji Akizawa, Kasumi Hayasaka, Tatsuya Fukumoto, Keisuke Taki, Yusuke Niinuma, Takehiro Yamada, Reiko Oyamada, Tsubasa Watanabe, Sho Nakakubo, Chiaki Watanabe, Takanori Teshima, Nobuhisa Ishiguro
Antimicrobial stewardship & healthcare epidemiology : ASHE, 3, 1, e209, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, The detection rate of multidrug-resistant Pseudomonas aeruginosa in patients admitted to 2 wards and the intensive care unit decreased from 20.3% (129 of 636 isolates) to 4.2% (37 of 889 isolates) after the start of disinfection of hand washing sinks using alkyl diaminoethylglycine hydrochloride.

Clinical features of complex karyotype in newly diagnosed acute myeloid leukemia
Shota Yoshida, Masahiro Onozawa, Naoki Miyashita, Hiroyuki Kimura, Shogo Takahashi, Shota Yokoyama, Toshihiro Matsukawa, Shinsuke Hirabayashi, Akio Mori, Daisuke Hidaka, Koichiro Minauchi, Akio Shigematsu, Junichi Hashiguchi, Tetsuyuki Igarashi, Yasutaka Kakinoki, Yutaka Tsutsumi, Makoto Ibata, Hajime Kobayashi, Yoshihito Haseyama, Katsuya Fujimoto, Toshimichi Ishihara, Hajime Sakai, Shuichi Ota, Takeshi Kondo, Takanori Teshima
International Journal of Hematology, 117, 4, 544, 552, Springer Science and Business Media LLC, 2022年12月26日, ［査読有り］, ［最終著者］, ［国内誌］
英語, 研究論文（学術雑誌）, Complex karyotype acute myeloid leukemia (CK-AML) has been classified as an adverse-risk subtype. Although a few reports have further classified CK-AML as typical (including monosomy of chromosomes 5, 7 and 17 or deletion of 5q, 7q and/or 17p) or atypical, the clinical features of these subtypes in Japanese patients remain unclear. We retrospectively analyzed a total of 115 patients with CK-AML, including 77 with typical CK-AML and 38 with atypical CK-AML. Median overall survival (OS) was significantly shorter in patients with typical CK-AML than atypical CK-AML (143 days vs. 369 days, P = 0.009). Among patients with typical CK-AML, those with monosomy 17 or deletion of 17p had significantly shorter OS than patients without such abnormalities (105 days vs. 165 days, P = 0.033). TP53 mutations were more predominant in patients with typical CK-AML than in patients with atypical CK-AML (69.7% vs. 32.4%, P < 0.001). Patients with typical CK-AML had a poor prognosis regardless of TP53 mutation status. Among patients with atypical CK-AML, however, prognosis was worse for those with the TP53 mutation than those without the mutation. In conclusion, prognosis is extremely poor for both typical CK-AML and atypical CK-AML with TP53 mutation.

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, 590, 597, Springer Science and Business Media LLC, 2022年12月14日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees
Takeshi Inoue, Ryo Shinnakasu, Chie Kawai, Hiromi Yamamoto, Shuhei Sakakibara, Chikako Ono, Yumi Itoh, Tommy Terooatea, Kazuo Yamashita, Toru Okamoto, Noritaka Hashii, Akiko Ishii-Watabe, Noah S. Butler, Yoshiharu Matsuura, Hisatake Matsumoto, Shinya Otsuka, Kei Hiraoka, Takanori Teshima, Masaaki Murakami, Tomohiro Kurosaki
Journal of Experimental Medicine, 220, 2, Rockefeller University Press, 2022年12月13日, ［査読有り］
研究論文（学術雑誌）, In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, a third dose elicits potent neutralizing activity against the Omicron variant. To address the underlying mechanism for this differential antibody response, we examined spike receptor-binding domain (RBD)–specific memory B cells in vaccinated individuals. Frequency of Omicron-reactive memory B cells increased ∼9 mo after the second vaccine dose. These memory B cells show an altered distribution of epitopes from pre-second memory B cells, presumably due to an antibody feedback mechanism. This hypothesis was tested using mouse models, showing that an addition or a depletion of RBD-induced serum antibodies results in a concomitant increase or decrease, respectively, of Omicron-reactive germinal center (GC) and memory B cells. Our data suggest that pre-generated antibodies modulate the selection of GC and subsequent memory B cells after the second vaccine dose, accumulating more Omicron-reactive memory B cells over time, which contributes to the generation of Omicron-neutralizing antibodies elicited by the third vaccine dose.

Ultrasonographic monitoring of sinusoidal obstruction syndrome in patients treated with inotuzumab ozogamicin.
Takahito Iwai, Mutsumi Nishida, Junichi Sugita, Atsushi Yasumoto, Yuta Hasegawa, Tomoko Morimoto, Daishi Nakayama, Kohei Okada, Akio Mori, Takanori Teshima
International journal of hematology, 116, 6, 973, 975, 2022年12月, ［国内誌］
英語

Clinical Pharmacology and Determinants of Response to UCART19, an Allogeneic Anti-CD19 CAR-T Cell Product, in Adult B-cell Acute Lymphoblastic Leukemia
Sandra Dupouy, Ibtissam Marchiq, Thibaud Derippe, Maria Almena-Carrasco, Agnieszka Jozwik, Sylvain Fouliard, Yasmina Adimy, Julia Geronimi, Charlotte Graham, Nitin Jain, Marcela V. Maus, Mohamad Mohty, Nicolas Boissel, Takanori Teshima, Koji Kato, Reuben Benjamin, Svetlana Balandraud
Cancer Research Communications, 2, 11, 1520, 1531, American Association for Cancer Research (AACR), 2022年11月30日, ［査読有り］
研究論文（学術雑誌）, Background:

UCART191 is an “off-the-shelf” genome-edited anti-CD19 chimeric antigen receptor (CAR)-T cell product, manufactured from unrelated healthy donor cells.

Methods:

UCART19 was administered to 25 adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) in the CALM trial. All patients underwent lymphodepletion with fludarabine and cyclophosphamide ± alemtuzumab and received one of three ascending doses of UCART19. Given the allogeneic nature of UCART19, we analyzed the impact of lymphodepletion, HLA disparities, and host immune system reconstitution on its kinetics, along with other factors known to affect autologous CAR-T cell clinical pharmacology.

Results:

Responder patients (12/25) had higher UCART19 expansion (Cmax) and exposure (AUCTlast) than nonresponders (13/25), as measured by transgene levels in peripheral blood. The persistence of CAR+ T cells did not exceed 28 days in 10/25 patients and lasted beyond 42 days in 4/25. No significant correlation was found between UCART19 kinetics and administered cell dose, patient and product characteristics or HLA disparities. However, the number of prior lines of therapy and absence of alemtuzumab negatively impacted UCART19 expansion and persistence. Alemtuzumab exposure positively affected IL7 and UCART19 kinetics, while negatively correlating with host T lymphocyte AUC0-28.

Conclusions:

UCART19 expansion is a driver of response in adult patients with R/R B-ALL. These results shed light on the factors associated with UCART19 kinetics, which remain highly affected by the impact of alemtuzumab on IL7 and host-versus-graft rejection.

Significance:

First description of the clinical pharmacology of a genome-edited allogeneic anti-CD19 CAR-T cell product showing the crucial role of an alemtuzumab-based regimen in sustaining UCART19 expansion and persistence through increased IL7 availability and decreased host T lymphocyte population.

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

Humoral response to mRNA-based COVID-19 vaccine in patients with immune thrombocytopenia
Akio Mori, Masahiro Onozawa, Mirei Kobayashi, Shihori Tsukamoto, Hajime Senjo, Takashi Ishio, Emi Yokoyama, Koh Izumiyama, Makoto Saito, Haruna Muraki, Masanobu Morioka, Takanori Teshima, Takeshi Kondo
British Journal of Haematology, 200, 6, 717, 721, Wiley, 2022年11月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Data for COVID-19 vaccine response in patients with immune thrombocytopenia (ITP) are very limited. In a study of 28 patients with ITP, anti-severe acute respiratory syndrome coronavirus 2 spike antibody titres were measured after vaccination. The seroconversion rate for ITP patients was 91.3%, comparable to that in healthy controls (HCs). However, the antibody titre in ITP patients was significantly lower than that in HCs and declined with ageing. Furthermore, the antibody titre in ITP patients who received a minimum prednisolone dose of at least 5 mg/day at any time-point at or after initial vaccination was lower than that in other patients.

Efficacy and safety of tisagenlecleucel in adult Japanese patients with relapsed or refractory follicular lymphoma: results from the phase 2 ELARA trial.
Noriko Fukuhara, Koji Kato, Hideki Goto, Tajima Takeshi, Mayu Kawaguchi, Kota Tokushige, Koichi Akashi, Takanori Teshima, Hideo Harigae, Stephen J Schuster, Catherine Thieblemont, Martin Dreyling, Nathan Fowler
International journal of hematology, 117, 2, 251, 259, 2022年11月21日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Tisagenlecleucel yielded a high durable response rate in patients with relapsed/refractory (r/r) follicular lymphoma (FL) in the global phase 2 ELARA trial. Here, we report the efficacy, safety, and cellular kinetics of tisagenlecleucel in a subgroup of Japanese patients with r/r FL from ELARA. METHODS: ELARA (NCT03568461) is a global single-arm trial of tisagenlecleucel in patients with r/r FL who received ≥ 2 prior lines of therapy. The primary endpoint was the complete response rate (CRR), and the secondary endpoints were the overall response rate, duration of response, progression-free survival, overall survival, safety, and cellular kinetics. RESULTS: As of March 29, 2021, nine Japanese patients were enrolled and received tisagenlecleucel with a median follow-up of 13.6 months (range, 10.5‒19.3). Per independent review committee, CRR was 100% (95% CI 63.1‒100). Within 8 weeks of infusion, cytokine release syndrome (CRS) of any grade was reported in 6 patients (66.7%); however, no grade ≥ 3 CRS or any grade serious neurological events or treatment-related deaths were observed. CONCLUSION: Tisagenlecleucel showed high efficacy and manageable safety in adult Japanese patients with r/r FL. Moreover, the clinical outcomes were similar to the global population, which supports the potential of tisagenlecleucel in Japanese patients with r/r FL.

A phase 2 study of axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma in Japan: 1-year follow-up and biomarker analysis.
Koji Kato, Nobuharu Fujii, Shinichi Makita, Hideki Goto, Junya Kanda, Kazuyuki Shimada, Koichi Akashi, Koji Izutsu, Takanori Teshima, Natsuko Fukuda, Tokuhito Sumitani, Shota Nakamura, Hiroyuki Sumi, Shinji Shimizu, Yasuyuki Kakurai, Kenji Yoshikawa, Kensei Tobinai, Noriko Usui, Kiyohiko Hatake
International journal of hematology, 2022年11月18日, ［国内誌］
英語, 研究論文（学術雑誌）, Axicabtagene ciloleucel (axi-cel) is an autologous, CD19-targeting chimeric antigen receptor T‑cell therapy. We recently reported the 3-month follow-up results of a phase 2, multicenter, open‑label, single-arm study of axi-cel in Japanese patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) (JapicCTI-183914). Here, we present 1-year efficacy and safety data and biomarker analysis data regarding mechanisms of resistance to axi-cel. Primary and secondary endpoints included investigator-assessed objective response rate (ORR), serious adverse events, and treatment-emergent adverse events. Axi-cel pharmacokinetics were also examined. Biomarker analysis was performed by cytokine measurement, immunohistochemistry, RNA sequencing, and whole-exome sequencing. At a median follow-up of 13.4 months, ORR was 86.7% (13/15 patients), and the complete response (CR) rate improved to 53.3% (8/15 patients) due to response conversion. Seven patients experienced disease progression, and one achieved CR after re-treatment with axi-cel. No new safety concerns were detected. Plausible resistance mechanisms to axi-cel varied among patients but included CD19 downregulation, programmed death-ligand 1 upregulation, and increased macrophage and angiogenesis signatures. The 1-year efficacy and safety of axi-cel were confirmed in Japanese patients with R/R LBCL. Resistance to treatment may involve multiple factors, including target antigen loss and an unfavorable tumor environment.Clinical trial registration: Japan Clinical Trials Information; JapicCTI-183914.

Frequencies of Anti-Troponin I vs Anti-Troponin T Autoantibodies and Degrees of Interference on Troponin Assays.
Keiichi Nakano, Satoshi Sugawa, Masanori Seimiya, Satoshi Murakami, Keiko Yasuda, Chiaki Watanabe, Hideki Goto, Takanori Teshima
Laboratory medicine, 2022年11月02日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Presence of autoantibodies against troponin I (cTnI) or T (cTnT) has been reported to interfere with troponin assays. However, the extent of the interference with the measurement has not been explored sufficiently. The aims of this study were to examine the frequencies of autoantibodies against troponin I and troponin T and how much these antibodies would affect the measurement. METHODS: The study comprised 52 subjects who visited Hokkaido University Hospital with suspected ischemic heart diseases. To evaluate the presence of autoantibodies, we calculated the recoveries of cTnI or cTnT after immunoglobulin G depletion, and the distributions of peaks reactive with cTnI or cTnT by high-performance liquid chromatography were examined. RESULTS: Autoantibodies against cTnI and cTnT were identified in 8 subjects (15.4%) and 1 subject (1.9%), respectively. Although the greatest difference between cTnI and cTnT was 32-fold, the distributions of cTnI-to-cTnT ratios in groups with and without anti-cTnI were not statistically different. CONCLUSION: Autoantibodies against cTnI were more frequent by several fold than those against cTnT. Their presence did not significantly expand the discrepancy between cTnI and cTnT assays.

2021年度HIV-1薬剤耐性検査外部精度評価の報告　　　　　　　　　　　　　　　
吉田 繁, 松田 昌和, 今橋 真弓, 岡田 清美, 齊藤 浩一, 林田 庸総, 佐藤 かおり, 藤澤 真一, 遠藤 知之, 西澤 雅子, 椎野 禎一郎, 潟永 博之, 豊嶋 崇徳, 杉浦 亙, 吉村 和久, 菊地 正
日本エイズ学会誌, 24, 4, 401, 401, (一社)日本エイズ学会, 2022年11月
日本語

国内HIV-1CRF07_BCの流行動向に関する研究　　　　　　　　　　　　　　　
大谷 眞智子, 椎野 禎一郎, 西澤 雅子, 林田 庸総, 潟永 博之, 豊嶋 崇徳, 渡邊 大, 今橋 真弓, 俣野 哲朗, 菊地 正
日本エイズ学会誌, 24, 4, 438, 438, (一社)日本エイズ学会, 2022年11月
日本語

2021年の国内新規診断未治療HIV感染者・AIDS患者における薬剤耐性HIV-1の動向　　　　　　　　　　　　　　　
菊地 正, 西澤 雅子, 小島 潮子, 大谷 眞智子, 椎野 禎一郎, 俣野 哲朗, 佐藤 かおり, 豊嶋 崇徳, 伊藤 俊広, 林田 庸総, 潟永 博之, 岡 慎一, 古賀 道子, 長島 真美, 貞升 健志, 近藤 真規子, 宇野 俊介, 谷口 俊文, 猪狩 英俊, 寒川 整, 中島 秀明, 吉野 友祐, 堀場 昌英, 茂呂 寛, 渡邉 珠代, 蜂谷 敦子, 今橋 真弓, 松田 昌和, 重見 麗, 岡崎 玲子, 岩谷 靖雅, 横幕 能行, 渡邊 大, 阪野 文哉, 森 治代, 藤井 輝久, 高田 清式, 中村 麻子, 南 留美, 山本 政弘, 松下 修三, 饒平名 聖, 仲村 秀太, 健山 正男, 藤田 次郎, 吉村 和久, 杉浦 亙
日本エイズ学会誌, 24, 4, 401, 401, (一社)日本エイズ学会, 2022年11月
日本語

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, 2022年11月
日本語

SARS-CoV-2 Omicron detection by antigen tests using saliva.
Kaoru Murakami, Sumio Iwasaki, Satoshi Oguri, Kumiko Tanaka, Rigel Suzuki, Kasumi Hayasaka, Shinichi Fujisawa, Chiaki Watanabe, Satoshi Konno, Isao Yokota, Takasuke Fukuhara, Masaaki Murakami, Takanori Teshima
Journal of clinical virology plus, 2, 4, 100109, 100109, 2022年11月, ［国際誌］
英語, 研究論文（学術雑誌）, The Omicron emerged in November 2021 and became the predominant SARS-CoV-2 variant globally. It spreads more rapidly than ancestral lineages and its rapid detection is critical for the prevention of disease outbreaks. Antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) yield results more quickly than standard polymerase chain reaction (PCR). However, their utility for the detection of the Omicron variant remains unclear. We herein evaluated the performance of ICA and CLEIA in saliva from 51 patients with Omicron and 60 PCR negative individuals. The sensitivity and specificity of CLEIA were 98.0% (95%CI: 89.6-100.0%) and 100.0% (95%CI: 94.0-100.0%), respectively, with fine correlation with cycle threshold (Ct) values. The sensitivity and specificity of ICA were 58.8% (95%CI: 44.2-72.4%) and 100.0% (95%CI: 94.0-100.0%), respectively. The sensitivity of ICA was 100.0% (95%CI: 80.5-100.0%) when PCR Ct was less than 25. The Omicron can be efficiently detected in saliva by CLEIA. ICA also detects high viral load Omicron using saliva.

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, 2022年10月15日, ［国際誌］
英語

UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial.
Reuben Benjamin, Nitin Jain, Marcela V Maus, Nicolas Boissel, Charlotte Graham, Agnieszka Jozwik, Deborah Yallop, Marina Konopleva, Matthew J Frigault, Takanori Teshima, Koji Kato, Floriane Boucaud, Svetlana Balandraud, Athos Gianella-Borradori, Florence Binlich, Ibtissam Marchiq, Sandra Dupouy, Maria Almena-Carrasco, Matthieu Pannaux, Sylvain Fouliard, Eolia Brissot, Mohamad Mohty
The Lancet. Haematology, 2022年10月10日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The prognosis for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia remains poor. UCART19, an allogeneic genome-edited anti-CD19 chimeric antigen receptor (CAR) T-cell product derived from healthy donors and available for immediate clinical use, offers a potential therapeutic option for such patients. The CALM trial is a first-in-human study evaluating the safety and antileukaemic activity of UCART19 in adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. METHODS: This phase 1, open-label study was conducted at eight centres across France, the UK, the USA, and Japan. Adult patients aged 16-70 years with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukaemia who had morphological relapse or a minimal residual disease level of at least 1 × 10-3 and had exhausted standard treatment options were enrolled in the study, which comprised a dose-escalation phase of up to three UCART19 doses followed by a safety expansion phase. Patients underwent lymphodepletion with fludarabine (30 mg/m2 per day intravenously for 3 days) and cyclophosphamide (500 mg/m2 per day intravenously for 3 days) with or without alemtuzumab (1 mg/kg or 40 mg or 60 mg over 5 days) and received UCART19 doses of 6 × 106, 6-8 × 107, or 1·8-2·4 × 108 total CAR T cells intravenously, followed by safety evaluation and disease response assessments. The primary endpoint was incidence and severity of adverse events. Secondary endpoints were the overall response rate, duration of response, relapse-free survival, progression-free survival, and overall survival. This trial is registered with ClinicalTrials.gov (NCT02746952) and is complete. FINDINGS: Between Aug 1, 2016, and June 30, 2020, 25 patients were enrolled in the study and treated with UCART19. Median duration of follow-up was 12·8 months (IQR 2·8-24·8). Median age was 37 years (IQR 28-45). 14 (56%) patients were male and 11 (44%) female. 17 (68%) patients were White, two (8%) Black, two (8%) Asian, and four (16%) from other racial or ethnic groups. Three patients developed dose-limiting toxicities (one at each dose level); one had grade 4 cytokine release syndrome and two had grade 4 prolonged cytopenias. Grade 3 or higher cytokine release syndrome was reported in six (24%) patients and grade 3 or higher neurological toxicity in one (4%) patient. Grade 3 or higher infections occurred in seven (28%) patients, and grade 4 prolonged cytopenia in four (16%) patients. Two (8%) patients developed grade 1 acute cutaneous graft-versus-host disease. 14 patients died, nine from progressive disease and five from infections or other complications, of which four were considered to be related to UCART19 or lymphodepletion, or both. After a median of follow-up of 12·8 months (IQR 2·8-24·8), overall response rate was 48% (95% CI 28-69; 12 of 25 patients), duration of response and median relapse-free survival were 7·4 months (95% CI 1·8 to not calculable), progression-free survival was 2·1 months (95% CI 1·2-2·8), and overall survival was 13·4 months (95% CI 4·8-23·0). INTERPRETATION: UCART19 had a manageable safety profile, and showed evidence of antileukaemic activity in heavily pretreated adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. This study shows that allogeneic off-the-shelf CAR T cells can be used safely to treat patients with relapsed B-cell acute lymphoblastic leukaemia. FUNDING: Servier.

Neurolymphomatosis in Intravascular Large B-cell Lymphoma.
Toru Miyajima, Hiroyuki Ohigashi, Hiroaki Yaguchi, Takanori Teshima
Internal medicine (Tokyo, Japan), 2022年10月05日, ［国内誌］
英語, 研究論文（学術雑誌）

出血性膀胱炎において尿中ウイルス感染細胞が認められた同種造血幹細胞移植後の3症例
猪股 百華, 中野 恵一, 小林 美穂, 大沼 麗子, 山下 亜妃子, 原田 晋平, 吉田 匠汰, 宮島 徹, 渡邊 千秋, 後藤 秀樹, 豊嶋 崇徳
日本臨床検査医学会誌, 70, 補冊, 222, 222, (一社)日本臨床検査医学会, 2022年10月
日本語

DLBCLにおける適切なエンドポイントはEFS36である　　　　　　　　　　　　　　　
泉山 康, 稲尾 翼, 後藤 秀樹, 原田 晋平, 千丈 創, 須藤 啓斗, 橋口 淳一, 小笠原 励起, 佐賀 智之, 五十嵐 哲祥, 若狭 健太郎, 笠原 郁美, 武田 紫, 山口 圭介, 重松 明男, 高畑 むつみ, 藤本 勝也, 長谷山 美仁, 永嶋 貴博, 酒井 基, 柿木 康孝, 黒澤 光俊, 横田 勲, 豊嶋 崇徳
日本血液学会学術集会, 84回, 916, 916, (一社)日本血液学会, 2022年10月
英語

Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis.
Rima M Saliba, Amin M Alousi, Joseph Pidala, Mukta Arora, Stephen R Spellman, Michael T Hemmer, Tao Wang, Camille Abboud, Sairah Ahmed, Joseph H Antin, Amer Beitinjaneh, David Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choe, Rabi Hanna, Peiman Hematti, Rammurti T Kamble, Carrie L Kitko, Mary Laughlin, Lazaros Lekakis, Margaret L MacMillan, Rodrigo Martino, Parinda A Mehta, Taiga Nishihori, Sagar S Patel, Miguel-Angel Perales, Hemalatha G Rangarajan, Olov Ringdén, Joseph Rosenthal, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Takanori Teshima, Marjolein van der Poel, Leo F Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A Yared, Jeffrey Schriber, Richard E Champlin, Stefan O Ciurea
Transplantation and cellular therapy, 28, 10, 681, 693, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）, Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P = .001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P = .01), and chronic GI GvHD (21% versus 31%, P = .006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGvHD rate after Haplo/PTCY was also lower (hazard ratio [HR] = .4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR = .6, P = .01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR = .6, P = .04). Mortality rate was higher (HR = 1.6, P = .03) during, but not after (HR = .9, P = .6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.

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, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma: an open-label, multicenter, dose-escalation phase 1 study.
Hideki Goto, Koji Izutsu, Daisuke Ennishi, Yuko Mishima, Shinichi Makita, Koji Kato, Miyoko Hanaya, Satoshi Hirano, Kazuya Narushima, Takanori Teshima, Hirokazu Nagai, Kenichi Ishizawa
International journal of hematology, 116, 6, 911, 921, 2022年09月15日, ［国内誌］
英語, 研究論文（学術雑誌）, The selective phosphatidylinositol 3-kinase δ inhibitor zandelisib demonstrated favorable safety and efficacy [objective response rate (ORR) 79%] in patients with B-cell malignancies in a phase 1b study in the US and Switzerland. In this phase 1 dose-escalation study (NCT03985189), 9 Japanese patients with relapsed/refractory indolent non-Hodgkin's lymphoma (R/R iNHL) received zandelisib on a continuous daily schedule (45 or 60 mg) until progressive disease/unacceptable toxicity. No dose-limiting toxicities were observed. The maximum tolerated dose was not reached. At a median follow-up of 17.5 months, Grade ≥ 3 treatment-emergent adverse events that occurred in 2 or more patients were neutrophil count decreased (55.6%; 5/9) and diarrhea (33.3%; 3/9). Immune-related toxicities, including hepatobiliary disorder, aspartate/alanine aminotransferase increased, diarrhea/colitis, organizing pneumonia, stomatitis, and rash, led to zandelisib discontinuation in 4 patients. The investigator-assessed ORR, based on modified Lugano criteria, was 100%, including 2 complete responses (22.2%; in follicular lymphoma patients receiving 60 mg/day). Median duration of response, progression-free survival, and time to response were 7.9, 11.1, and 1.9 months, respectively. Zandelisib demonstrated a manageable safety profile at 60 mg, the recommended phase 2 dose (RP2D) in Japanese patients. The RP2D resulted in favorable pharmacokinetics and anti-tumor efficacy in Japanese patients with R/R iNHL.Trial registration. NCT03985189 (ClinicalTrials.gov).

Humoral response to mRNA-based COVID-19 vaccine in patients with de novo and pre-existing immune thrombocytopenia with exacerbation of thrombocytopenia after vaccination.
Akio Mori, Masahiro Onozawa, Mirei Kobayashi, Shihori Tsukamoto, Takashi Ishio, Emi Yokoyama, Koh Izumiyama, Makoto Saito, Haruna Muraki, Masanobu Morioka, Takanori Teshima, Takeshi Kondo
British journal of haematology, 2022年09月12日, ［国際誌］
英語

Comparable survival outcomes with haploidentical stem cell transplantation and unrelated bone marrow transplantation.
Yoshiko Atsuta, Junichi Sugita, Hirohisa Nakamae, Yumiko Maruyama, Ken Ishiyama, Souichi Shiratori, Takahiro Fukuda, Mio Kurata, Naoki Shingai, Yukiyasu Ozawa, Masayoshi Masuko, Koji Nagafuji, Satoru Takada, Shinichi Kako, Yoshinobu Kanda, Junya Kanda, Tatsuo Ichinohe, Takanori Teshima
Bone marrow transplantation, 57, 12, 1781, 1787, 2022年09月12日, ［国際誌］
英語, 研究論文（学術雑誌）, We retrospectively compared outcomes of unrelated donor bone marrow transplant (UBMT) and HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) using the Japanese registry data. Recipients of first HCT for acute leukemia and myelodysplastic syndromes between 2012 and 2015 were included. The analyzed subjects comprised UBMT recipients with 8/8 matched HLA alleles (n = 1470), 7/8 matched alleles (n = 859), 6/8 matched alleles (n = 186), and recipients of PTCy-haploPBSCT (n = 133). In multivariate analyses with 8/8 matched UBMT as the reference, PTCy-haploPBSCT showed similar overall mortality, decreased risk of non-relapse mortality (NRM), increased risk of relapse, and decreased risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD. Adjusted probabilities for 8/8 matched UBMT, PTCy-haploPBSCT, and 7/8 and 6/8 matched UBMT groups at 2 years post-transplant were 61%, 60%, 58%, and 52% for overall survival, 23%, 28%, 21%, and 19% for relapse, and 20%, 7%, 24%, and 33% for NRM. PTCy-haploPBSCT was associated with remarkably low NRM, contributing to survival outcomes that were comparable to 8/8 matched UBMT. The higher relapse rate in the PTCy-haploPBSCT group might be associated with the higher proportion of high-risk patients. PTCy-haploPBSCT may be a viable alternative when HLA-matched related donors are not available.

Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 (phase 2) Japanese cohort.
Masaki Ri, Kenshi Suzuki, Tadao Ishida, Junya Kuroda, Taku Tsukamoto, Takanori Teshima, Hideki Goto, Carolyn C Jackson, Huabin Sun, Lida Pacaud, Ei Fujikawa, Tzu-Min Yeh, Tomoyoshi Hatayama, Kensuke Aida, Yoshihiro Sunagawa, Shinsuke Iida
Cancer science, 2022年09月02日, ［国際誌］
英語, 研究論文（学術雑誌）, Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen have shown positive responses in patients with multiple myeloma (MM). The phase 2 portion of the CARTITUDE-1 study of ciltacabtagene autoleucel (cilta-cel) included a cohort of Japanese patients with relapsed/refractory MM. Following a conditioning regimen of cyclophosphamide (300 mg/m2 ) and fludarabine (30 mg/m2 ), patients received a single cilta-cel infusion at a target dose of 0.75 × 106 (range, 0.5-1.0 × 106 ) CAR-positive viable T cells/kg. The primary endpoint was overall response rate (ORR; defined as partial response or better) by International Myeloma Working Group criteria. A key secondary endpoint was the rate of very good partial response (VGPR) or better (defined as VGPR, complete response, stringent complete response). This first analysis was performed at 6 months after the last patient received cilta-cel. Thirteen patients underwent apheresis, nine of whom received cilta-cel infusion. Eight patients who received cilta-cel at the target dose responded, yielding an ORR of 100%. Seven of eight (87.5%) patients achieved a VGPR or better. One additional patient who received a below-target dose of cilta-cel also achieved a best response of VGPR. MRD negativity (10-5 threshold) was achieved in all six evaluable patients. Eight of nine (88.9%) patients who received cilta-cel infusion experienced a grade 3 or 4 adverse event, and eight (88.9%) patients experienced cytokine release syndrome (all grade 1 or 2). No CAR-T cell neurotoxicity was reported. A positive benefit/risk profile for cilta-cel was established for heavily pretreated Japanese patients with relapsed or refractory MM.

IgG4-IgE複合体の存在と臨床的意義の解明に向けた解析　　　　　　　　　　　　　　　
中野 恵一, 杉田 純一, 清宮 正徳, 安田 慶子, 渡邊 千秋, 後藤 秀樹, 豊嶋 崇徳
臨床化学, 51, Suppl.1, 223, 223, (一社)日本臨床化学会, 2022年09月
日本語

Serum levels of albumin and creatinine predict the outcome of sinusoidal obstruction syndrome after allogeneic HSCT.
Souichi Shiratori, Kohei Okada, Satomi Matsuoka, Shinichi Ito, Junichi Sugita, Takanori Teshima
Annals of hematology, 101, 9, 2117, 2118, 2022年09月, ［国際誌］
英語

Creation of Philadelphia chromosome by CRISPR/Cas9-mediated double cleavages on BCR and ABL1 genes as a model for initial event in leukemogenesis.
Minori Tamai, Shinichi Fujisawa, Thao T T Nguyen, Chiaki Komatsu, Keiko Kagami, Kenji Kamimoto, Kohei Omachi, Shin Kasai, Daisuke Harama, Atsushi Watanabe, Koshi Akahane, Kumiko Goi, Kazuhito Naka, Tadashi Kaname, Takanori Teshima, Takeshi Inukai
Cancer gene therapy, 2022年08月23日, ［国際誌］
英語, 研究論文（学術雑誌）, The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was obtained. In the subline, p210 BCR::ABL1 and its reciprocal ABL1::BCR fusions were generated as a result of balanced translocation corresponding to the Ph chromosome. Another set of sgRNAs targeting intron 1 of the BCR gene and intron 1 of the ABL1 gene induced a factor-independent subline expressing p190 BCR::ABL1. Both p210 and p190 BCR::ABL1 induced factor-independent growth by constitutively activating intracellular signaling pathways for transcriptional regulation of cell cycle progression and cell survival that are usually regulated by GM-CSF. These observations suggested that simultaneous DSBs at the BCR and ABL1 gene breakpoints are initiation events for oncogenesis in Ph+ leukemia. (200/200 words).

Comparable survival outcomes with haploidentical stem cell transplantation and cord blood transplantation.
Junichi Sugita, Yoshiko Atsuta, Hirohisa Nakamae, Yumiko Maruyama, Ken Ishiyama, Souichi Shiratori, Takahiro Fukuda, Mio Kurata, Naoki Shingai, Yukiyasu Ozawa, Masayoshi Masuko, Koji Nagafuji, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Junya Kanda, Takafumi Kimura, Tatsuo Ichinohe, Takanori Teshima
Bone marrow transplantation, 57, 11, 1681, 1688, 2022年08月20日, ［国際誌］
英語, 研究論文（学術雑誌）, HLA-haploidentical stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) and umbilical cord blood transplantation (UCBT) are alternative to HLA-matched stem cell transplantation. We conducted a matched-pair analysis of PTCy-haplo and UCBT using the Japanese registry data. We identified 136 patients aged between 16 and 69 years who received PTCy-haplo as their first transplantation for acute leukemia or myelodysplastic syndromes. Control group included 408 UCBT recipients selected to match the PTCy-haplo group. Overall and relapse-free survival probabilities at 2 years were comparable between the PTCy-haplo and UCBT groups: 55% vs. 53% for overall survival (p = 0.46), and 47% vs. 48% for relapse-free survival (p = 0.79), respectively. The cumulative incidence of relapse was significantly higher (43% vs. 29%, respectively, p = 0.006), while the cumulative incidence of non-relapse mortality (NRM) was significantly lower (9% vs. 23%, respectively, p < 0.001) in the PTCy-haplo group. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was lower in the PTCy-haplo group compared to the UCBT group (29% vs. 41%, respectively, p = 0.016), while those of grade III-IV acute GVHD and chronic GVHD were not statistically different between the two groups. Our results suggest that both PTCy-haplo and UCBT are viable alternatives to HLA-matched stem cell transplantation.

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, 2022年08月03日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

非アルコール性脂肪肝・脂肪肝炎例におけるオートタキシンの肝線維化進行度評価の検討
西能 史華, 中野 恵一, 岩井 孝仁, 西田 睦, 安田 慶子, 渡邊 千秋, 後藤 秀樹, 豊嶋 崇徳
医療検査と自動化, 47, 4, 456, 456, (一社)日本医療検査科学会, 2022年08月
日本語

Ultrasonographic scoring system of late-onset sinusoidal obstruction syndrome/veno-occlusive disease after hematopoietic stem cell transplantation.
Mutsumi Nishida, Junichi Sugita, Takahito Iwai, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Ryosuke Sakano, Yuta Hasegawa, Atsushi Yasumoto, Yuko Cho, Takanori Teshima
Bone marrow transplantation, 57, 8, 1338, 1340, 2022年08月, ［国際誌］
英語

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

Long-term safety for patients with tisagenlecleucel-treated relapsed/refractory diffuse large B-cell lymphoma.
Ulrich Jaeger, Constantine S Tam, Peter Borchmann, Joseph P McGuirk, Marianne Johansen, Edmund K Waller, Samantha M Jaglowski, Charalambos Andreadis, Ronan Ronan Foley, Jason R Westin, Isabelle Fleury, P Joy Ho, Stephan Mielke, Takanori Teshima, Gilles Andre Salles, Stephen J Schuster, Fiona C He, Richard T Maziarz, Sebastian A Mayer, Shinichi Makita, Marie José Kersten, Monalisa Ghosh, Nina D Wagner-Johnston, Koji Kato, Paolo Corradini, Hideki Goto, Silvia Colicino, Abhijit Agarwal, Chiari Lobetti Lobetti-Bodoni, Michael R Bishop
Blood advances, 6, 16, 4816, 4820, 2022年06月10日, ［国際誌］
英語, 研究論文（学術雑誌）

IgG4-IgE complex in patients with IgG4-related disease.
Keiichi Nakano, Junichi Sugita, Masanori Seimiya, Keiko Yasuda, Chiaki Watanabe, Takanori Teshima
Clinica chimica acta; international journal of clinical chemistry, 531, 261, 264, 2022年06月01日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease characterized by high IgE levels; however, the physiological significance of elevated IgE levels in patients with IgG4-RD is unclear. Previously, we reported the formation of IgG4-IgE complex in IgG4-RD patients with elevated IgE levels. In this study, we examined the frequency of this complex formation and its relationship with the clinical features in IgG4-RD patients. METHODS: The IgG4-IgE complex was evaluated in 33 and 17 patients with and without IgG4-RD, respectively. The IgG4-IgE complex was evaluated by performing the immunoadsorption of IgG4 using anti-IgG4 antibody-conjugated matrices. RESULTS: The frequency of IgG4-IgE complex formation in patients with IgG4-RD was significantly higher than that in those without IgG4-RD (21.2% vs. 0%). No significant differences were observed between the groups in terms of clinical characteristics and laboratory data. However, the IgG4-IgE complex-positive group had a significantly higher frequency of pancreatic lesions (85.7% vs. 42.3%) and a significantly lower rate of retroperitoneal fiber/periarterial lesions (0% vs. 38.5%) than the IgG4-IgE complex-negative group. CONCLUSION: The IgG4-IgE complex was found only in patients with IgG4-RD which may provide some clues to the pathogenesis and etiology of IgG4-RD.

Humoral response to mRNA-based COVID-19 vaccine in patients with myeloid malignancies.
Akio Mori, Masahiro Onozawa, Shihori Tsukamoto, Takashi Ishio, Emi Yokoyama, Koh Izumiyama, Makoto Saito, Haruna Muraki, Masanobu Morioka, Takanori Teshima, Takeshi Kondo
British journal of haematology, 197, 6, 691, 696, 2022年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Data on the response to the COVID-19 vaccine in patients with myeloid malignancy, who are at severe risk in case of infection, have not emerged. In a study of 69 patients with myeloid malignancies, including 46 patients with acute myeloid leukaemia (AML) and 23 patients with myelodysplastic syndrome (MDS), anti-spike SARS-CoV-2 antibody titres were measured 3 months after the second mRNA-based vaccination. Seroconversion rates for AML and MDS were 94.7% and 100% respectively, with no significant difference from healthy controls (HCs). Patients with MDS showed a significantly lower antibody titre than that in HCs or AML patients. In AML patients, the antibody titres were comparable to those in HCs when treatment was completed, but lower in patients under maintenance therapy. The response to COVID-19 vaccine appears to be related to disease and treatment status. Patients with myeloid malignancies may be more responsive to vaccines than patients with lymphoid malignancies.

Dynamic change in peripheral blood WT1 mRNA levels within three cycles of azacitidine predict treatment response in patients with high-risk myelodysplastic syndromes.
Shinpei Harada, Masahiro Onozawa, Daisuke Hidaka, Shota Yokoyama, Hajime Senjo, Shogo Takahashi, Reiki Ogasawara, Minoru Kanaya, Akio Mori, Shuichi Ota, Takeshi Kondo, Takanori Teshima
Annals of hematology, 101, 6, 1239, 1250, 2022年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Azacitidine (AZA) improves overall survival (OS) in patients with high-risk myelodysplastic syndromes (MDS). However, predictive factors for response to AZA remain largely unknown. To elucidate whether dynamic change in peripheral blood (PB) Wilms' Tumor 1 (WT1) mRNA levels could predict response to AZA, we retrospectively identified 75 treatment-naïve patients with high-risk MDS who received at least 3 cycles of AZA. We classified patients into 4 groups, low-increase (LI), low-stable (LS), high-decrease (HD), and high-stable (HS) based on the dynamic change in PB WT1 mRNA levels within 3 cycles of AZA. Cumulative incidence of overall response after 10 cycles of AZA was significantly higher in LS/HD than in HS/LI (75.5% vs 4.5%, P < 0.001). The median OS for LS/HD was 18.2 months (95% CI, 12.8-28.1 months), whereas it was 11.6 months for HS/LI (95% CI, 6.6-14.1 months; P < 0.001). Multivariate analysis demonstrated that poor-/very poor-IPSS-R cytogenetic risk and HS/LI were independently associated with poor OS (poor-/very poor-IPSS-R cytogenetic risk: HR, 2.26; 95% CI, 1.10-4.68, P = 0.03, HS/LI: HR, 2.32; 95% CI, 1.21-4.46, P = 0.01). Patients with HS/LI did not show any further response to continuous AZA, and they should be considered for alternative therapy from earlier cycles.

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

MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.
Shinsuke Iida, Tadao Ishida, Toshihiro Miyamoto, Satoshi Teramukai, Heigoroh Shirai, Rie Kanamori, Yuki Tajima, Bruce Crawford, Jingbo Yi, Takanori Teshima
International journal of hematology, 116, 3, 411, 422, 2022年05月13日, ［国内誌］
英語, 研究論文（学術雑誌）, Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

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

IgG4-IgE complex in a patient with IgG4-related disease.
Keiichi Nakano, Junichi Sugita, Naoki Mafune, Masanori Seimiya, Keiko Yasuda, Chiaki Watanabe, Takanori Teshima
Clinica chimica acta; international journal of clinical chemistry, 528, 52, 55, 2022年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: IgE concentrations are occasionally elevated in patients with IgG4-related disease (IgG4-RD). In this report, we describe a novel case of IgG4-RD in which IgE concentrations were discordant between measuring reagents. CASE: An 81-year-old man was diagnosed with IgG4-RD and histological autoimmune pancreatitis, which ensued without treatment. The IgE concentrations measured using Elecsys IgE II Immunoassay and Iatroace IgE were 1287.0 IU/mL and 60.9 IU/mL, respectively. IgG4 concentration was 675 mg/dL. METHODS: To identify IgG and IgG4 directly bound to IgE, purification using protein G and anti-IgG4 antibody-conjugated matrixes and size-exclusion high-performance liquid chromatography (HPLC) were performed. RESULTS: In purification analysis, the IgE concentration of the flow-through and bound fractions were 6.8 IU/mL (10.8%) and 56.2 IU/mL (89.2%) for IgG purification and 6.8 IU/mL (12.2%) and 49.0 IU/mL (87.8%) for IgG4 purification. IgE was eluted as a single peak (640 kDa) using size-exclusion HPLC. In the elution pattern of IgG4, a minor peak (640 kDa) and a major peak (170 kDa) were observed. These results indicate that IgG4 binds to IgE and forms a complex, resulting in a discrepancy between reagents. CONCLUSIONS: In this report, we present an IgG4-IgE complex in a patient with IgG4-RD, which affected the discrepancy in IgE concentrations between IgE reagents. This report points to the significance of increased IgE production in IgG4-RD.

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, 2022年03月, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

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

Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial.
Nathan Hale Fowler, Michael Dickinson, Martin Dreyling, Joaquin Martinez-Lopez, Arne Kolstad, Jason Butler, Monalisa Ghosh, Leslie Popplewell, Julio C Chavez, Emmanuel Bachy, Koji Kato, Hideo Harigae, Marie José Kersten, Charalambos Andreadis, Peter A Riedell, P Joy Ho, José Antonio Pérez-Simón, Andy I Chen, Loretta J Nastoupil, Bastian von Tresckow, Andrés José María Ferreri, Takanori Teshima, Piers E M Patten, Joseph P McGuirk, Andreas L Petzer, Fritz Offner, Andreas Viardot, Pier Luigi Zinzani, Ram Malladi, Aiesha Zia, Rakesh Awasthi, Aisha Masood, Oezlem Anak, Stephen J Schuster, Catherine Thieblemont
Nature medicine, 28, 2, 325, 332, 2022年02月, ［国際誌］
英語, 研究論文（学術雑誌）, Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8-20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8-78.3) and ORR 86.2% (95% confidence interval, 77.5-92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.

Non-age-related neoplastic loss of sex chromosome correlated with prolonged survival in real-world CBF-AML patients.
Akio Mori, Masahiro Onozawa, Daisuke Hidaka, Shota Yokoyama, Toru Miyajima, Emi Yokoyama, Reiki Ogasawara, Koh Izumiyama, Makoto Saito, Shinichi Fujisawa, Shuichi Ota, Yasutaka Kakinoki, Yutaka Tsutsumi, Satoshi Yamamoto, Takuto Miyagishima, Takahiro Nagashima, Hiroshi Iwasaki, Hajime Kobayashi, Yoshihito Haseyama, Mitsutoshi Kurosawa, Masanobu Morioka, Takanori Teshima, Takeshi Kondo
International journal of hematology, 115, 2, 188, 197, 2022年02月, ［国内誌］
英語, 研究論文（学術雑誌）, In this real-world clinical study, in which we determined eligibility for allogenic hematopoietic stem cell transplantation by prognostic factors and minimal residual disease status, we retrospectively evaluated cytogenetic, genetic, and clinical features in 96 patients with core-binding factor acute myeloid leukemia (CBF-AML) including 62 patients with RUNX1/RUNX1T1 and 34 patients with CBFβ/MYH11. Multivariate analyses for 5-year overall survival (OS) in CBF-AML patients revealed that age of 50 years or older (HR: 3.46, 95% CI 1.47-8.11, P = 0.004) and receiving 2 or more induction cycles (HR: 3.55, 95% CI 1.57-8.05, P = 0.002) were independently associated with worse OS and that loss of sex chromosome (LOS) was independently associated with better OS (HR: 0.09, 95% CI 0.01-0.71, P = 0.022). At the time of complete remission, all 21 karyotyped patients with LOS had a normal karyotype. Furthermore, in all 9 patients with LOS who had a mosaic of metaphase cells with and without t(8;21) or inv(16), the metaphase cells without t(8;21)/inv(16) showed a normal karyotype. These results proved that LOS was not age-related and physiological, but rather a neoplastic chromosomal abnormality.

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

A Rare Case of BCL2-Positive Multiple Myeloma Complicated with Follicular Lymphoma.
Yutaka Tsutsumi, Shinich Ito, Mirei Kobayashi, Takanori Teshima
Case reports in hematology, 2022, 3076968, 3076968, 2022年, ［国際誌］
英語, A 68-year-old woman presented with follicular lymphoma complicated by IgG kappa-positive multiple myeloma. In this case, both follicular lymphoma and plasma cells were positive for BCL2 by immunostaining. T-cell association in the FL and MM was also analyzed in this case. Some CD3-positive T-cells were found around the plasma cells. These cells were mainly CD8-positive T-cells and not CD4-positive T-cells. These results suggest that CD4-positive T-cells were not associated with the proliferation of the plasma cells in this case. Although the FL that developed was initially positive for BCL2 protein, this does not indicate that plasma cells were derived from FL cells because of the eventual complication that occurred in this case. Furthermore, in this case, rituximab and bendamustine were effective for FL. They were not effective for MM, however, demonstrating that additional treatment options are necessary for the simultaneous treatment of BCL2-positive MM with FL.

Aleukemic Extramedullary Blast Crisis as an initial presentation of Chronic Myeloid Leukemia with E1A3 BCR-ABL1 Fusion Transcript
Naoki Miyashita, Masahiro Onozawa, Keito Suto, Shinichi Fujisawa, Nanase Okazaki, Daisuke Hidaka, Hiroyuki Ohigashi, Atsushi Yasumoto, Junichi Sugita, Daigo Hashimoto, Yoshihiro Matsuno, Takanori Teshima
Internal Medicine, Japanese Society of Internal Medicine, 2022年, ［査読有り］
研究論文（学術雑誌）

今月の特集 移植医療と臨床検査 造血幹細胞移植と臨床検査
安本 篤史, 加畑 馨, 豊嶋 崇徳
臨床検査, 65, 12, 1310, 1316, 株式会社医学書院, 2021年12月15日

【移植医療と臨床検査】造血幹細胞移植と臨床検査
安本 篤史, 加畑 馨, 豊嶋 崇徳
臨床検査, 65, 12, 1310, 1316, (株)医学書院, 2021年12月
日本語

Myelomonocytic differentiation of leukemic blasts accompanied by differentiation syndrome in a case of FLT3-ITD-positive AML treated with gilteritinib.
Takeshi Kondo, Masahiro Onozawa, Shinichi Fujisawa, Shinpei Harada, Reiki Ogasawara, Koh Izumiyama, Makoto Saito, Masanobu Morioka, Akio Mori, Takanori Teshima
Hematology (Amsterdam, Netherlands), 26, 1, 256, 260, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌）, Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in acute myelogenous leukemia (AML) and the mutation is associated with poor prognosis of patients. Two distinct types of activating mutations have been identified in AML samples. One is internal tandem duplications in the juxtamembrane domain (FLT3-ITD) and the other is point mutations in the tyrosine kinase domain (FLT3-TKD). Gilteritinib is a FLT3 inhibitor that inhibits both FLT3-ITD and FLT3-TKD. It was reported that differentiation of leukemic blasts accompanied by differentiation syndrome occurs in some patients treated with gilteritinib. However, information about the precise clinical course is limited, and appropriate management of differentiation syndrome has not been established. We report a case of relapsed AML with FLT3-ITD that was treated with gilteritinib. Analysis of the FLT3-ITD variant allele frequency (VAF) revealed that FLT3-ITD VAF was not decreased despite achievement of complete remission with incomplete hematologic recovery. Remarkable increases of monocytes and granulocytes accompanied by differentiation syndrome were observed at 6 months after the initiation of gilteritinib treatment. Intermittent chemotherapy with low-dose cytarabine and mitoxantrone was effective for reducing myelomonocytosis and resolving differentiation syndrome.

Equivalent SARS-CoV-2 viral loads by PCR between nasopharyngeal swab and saliva in symptomatic patients
Isao Yokota, Takeshi Hattori, Peter Y. Shane, Satoshi Konno, Atsushi Nagasaka, Kimihiro Takeyabu, Shinichi Fujisawa, Mutsumi Nishida, Takanori Teshima
Scientific Reports, 11, 1, 4500, 4500, Springer Science and Business Media LLC, 2021年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Emerging evidences have shown the utility of saliva for the detection of SARS-CoV-2 by PCR as alternative to nasopharyngeal swab (NPS). However, conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads between NPS and saliva in 42 COVID-19 patients. Viral loads were estimated by the cycle threshold (Ct) values. SARS-CoV-2 was detected in 34 (81%) using NPS with median Ct value of 27.4, and 38 (90%) using saliva with median Ct value of 28.9 (P = 0.79). Kendall’s W was 0.82, showing a high degree of agreement, indicating equivalent viral loads in NPS and saliva. After symptom onset, the Ct values of both NPS and saliva continued to increase over time, with no substantial difference. Self-collected saliva has a detection sensitivity comparable to that of NPS and is a useful diagnostic tool with mitigating uncomfortable process and the risk of aerosol transmission to healthcare workers.

Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in Adult T-cell leukemia/lymphoma.
Takashi Ishio, Sarvesh Kumar, Joji Shimono, Anusara Daenthanasanmak, Sigrid Dubois, Yuquan Lin, Bonita R Bryant, Michael N Petrus, Emmanuel Bachy, Da Wei Huang, Yandan Yang, Patrick L Green, Hiroo Hasegawa, Michiyuki Maeda, Hideki Goto, Tomoyuki Endo, Takashi Yokota, Kanako C Hatanaka, Yutaka Hatanaka, Shinya Tanaka, Yoshihiro Matsuno, Yibin Yang, Satoshi Hashino, Takanori Teshima, Thomas A Waldmann, Louis M Staudt, Masao Nakagawa
Blood, 139, 10, 1541, 1556, 2021年11月24日, ［国際誌］
英語, 研究論文（学術雑誌）, Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis with current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival of ATLL cells. As a single agent, the CDK6 inhibitor palbociclib induced cell cycle arrest and apoptosis in ATLL models with wild type TP53. ATLL models that had inactivated TP53 genetically were relatively resistant to palbociclib owing to compensatory CDK2 activity, and this resistance could be reversed by APR-246, a small molecule activator of mutant TP53. The CRISPR-Cas9 screen further highlighted the dependence of ATLL cells on mTORC1 signaling. Treatment of ATLL cells with palbociclib in combination with mTORC1 inhibitors was synergistically toxic irrespective of the TP53 status. This work defines CDK6 as a novel therapeutic target for ATLL and supports the clinical evaluation of palbociclib in combination with mTORC1 inhibitors in this recalcitrant malignancy.

Multiple introductions of SARS-CoV-2 B.1.1.214 lineages from mainland Japan preceded the third wave of the COVID-19 epidemic in Hokkaido.
Takako Shimura, Kodai Abe, Toshiki Takenouchi, Mamiko Yamada, Hisato Suzuki, Makoto Suematsu, Sho Nakakubo, Keisuke Kamada, Satoshi Konno, Takanori Teshima, Kenjiro Kosaki
Travel medicine and infectious disease, 44, 102210, 102210, 2021年11月22日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The third wave of the COVID-19 epidemic in the island of Hokkaido, the second largest island in Japan, began abruptly in October 2020. METHODS: We conducted a phylodynamic analysis of the SARS-CoV-2 genome sequences obtained from tertiary medical centers in the Greater Tokyo Area and Sapporo, the largest city in the island of Hokkaido, and genome sequences published by GISAID, an international SARS-CoV-2 genome database. We also analyzed the statistics on the person-nights of travelers in the island of Hokkaido from the Greater Tokyo Area in 2019 versus 2020. RESULTS: At least eight sub-lineages belonging to the B.1.1.214 lineage were introduced to the island of Hokkaido from the island of Honshu, the mainland of Japan from late July to November 2020, during the governmental travel promotion program. Five of the eight sub-lineages originated from the Greater Tokyo Area. Comparison of the monthly ratios of the person-nights of travelers in the island of Hokkaido from the Greater Tokyo Area in 2019 and 2020 revealed that the highest value occurred in October 2020. CONCLUSION: We contend that the Japanese governmental travel promotion program contributed to the introduction of the B.1.1.214 sub-lineages from the main island of Honshu to the island of Hokkaido, and drove the third wave in Hokkaido, even if we are unable to establish the causality.

E157Q変異を有する未治療HIV-1感染者におけるインテグラーゼ阻害薬をキードラッグとした抗HIV薬開始後の臨床経過　　　　　　　　　　　　　　　
宇野 俊介, 菊地 正, 林田 庸総, 今橋 真弓, 南 留美, 古賀 道子, 寒川 整, 渡邊 大, 藤井 輝久, 健山 正男, 松下 修三, 吉野 友祐, 遠藤 知之, 堀場 昌英, 谷口 俊文, 猪狩 英俊, 吉田 繁, 豊嶋 崇徳, 中島 秀明, 横幕 能行, 岩谷 靖雅, 蜂谷 敦子, 潟永 博之, 吉村 和久, 杉浦 亙
日本エイズ学会誌, 23, 4, 423, 423, (一社)日本エイズ学会, 2021年11月
日本語

Ruxolitinib for Chronic Graft-versus-Host Disease. Reply.
Robert Zeiser, Takanori Teshima, Franco Locatelli
The New England journal of medicine, 385, 17, 1631, 1632, 2021年10月21日, ［国際誌］
英語

Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study
Stephen J Schuster, Constantine S Tam, Peter Borchmann, Nina Worel, Joseph P McGuirk, Harald Holte, Edmund K Waller, Samantha Jaglowski, Michael R Bishop, Lloyd E Damon, Stephen Ronan Foley, Jason R Westin, Isabelle Fleury, P Joy Ho, Stephan Mielke, Takanori Teshima, Murali Janakiram, Jing-Mei Hsu, Koji Izutsu, Marie José Kersten, Monalisa Ghosh, Nina Wagner-Johnston, Koji Kato, Paolo Corradini, Marcela Martinez-Prieto, Xia Han, Ranjan Tiwari, Gilles Salles, Richard T Maziarz
The Lancet Oncology, 22, 10, 1403, 1415, Elsevier BV, 2021年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: In the primary analysis of the pivotal JULIET trial of tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, the best overall response rate was 52% and the complete response rate was 40% in 93 evaluable adult patients with relapsed or refractory aggressive B-cell lymphomas. We aimed to do a long-term follow-up analysis of the clinical outcomes and correlative analyses of activity and safety in the full adult cohort. METHODS: In this multicentre, open-label, single-arm, phase 2 trial (JULIET) done at 27 treatment sites in ten countries (Australia, Austria, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, and the USA), adult patients (≥18 years) with histologically confirmed relapsed or refractory large B-cell lymphomas who were ineligible for, did not consent to, or had disease progression after autologous haematopoietic stem-cell transplantation, with an Eastern Cooperative Oncology Group performance status of 0-1 at screening, were enrolled. Patients received a single intravenous infusion of tisagenlecleucel (target dose 5 × 108 viable transduced CAR T cells). The primary endpoint was overall response rate (ie, the proportion of patients with a best overall disease response of a complete response or partial response using the Lugano classification, as assessed by an independent review committee) at any time post-infusion and was analysed in all patients who received tisagenlecleucel (the full analysis set). Safety was analysed in all patients who received tisagenlecleucel. JULIET is registered with ClinialTrials.gov, NCT02445248, and is ongoing. FINDINGS: Between July 29, 2015, and Nov 2, 2017, 167 patients were enrolled. As of Feb 20, 2020, 115 patients had received tisagenlecleucel infusion and were included in the full analysis set. At a median follow-up of 40·3 months (IQR 37·8-43·8), the overall response rate was 53·0% (95% CI 43·5-62·4; 61 of 115 patients), with 45 (39%) patients having a complete response as their best overall response. The most common grade 3-4 adverse events were anaemia (45 [39%]), decreased neutrophil count (39 [34%]), decreased white blood cell count (37 [32%]), decreased platelet count (32 [28%]), cytokine release syndrome (26 [23%]), neutropenia (23 [20%]), febrile neutropenia (19 [17%]), hypophosphataemia (15 [13%]), and thrombocytopenia (14 [12%]). The most common treatment-related serious adverse events were cytokine release syndrome (31 [27%]), febrile neutropenia (seven [6%]), pyrexia (six [5%]), pancytopenia (three [3%]), and pneumonia (three [3%]). No treatment-related deaths were reported. INTERPRETATION: Tisagenlecleucel shows durable activity and manageable safety profiles in adult patients with relapsed or refractory aggressive B-cell lymphomas. For patients with large B-cell lymphomas that are refractory to chemoimmunotherapy or relapsing after second-line therapies, tisagenlecleucel compares favourably with respect to risk-benefit relative to conventional therapeutic approaches (eg, salvage chemotherapy). FUNDING: Novartis Pharmaceuticals.

Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma
Koji Kato, Shinichi Makita, Hideki Goto, Junya Kanda, Nobuharu Fujii, Kazuyuki Shimada, Koichi Akashi, Koji Izutsu, Takanori Teshima, Natsuko Fukuda, Tokuhito Sumitani, Hiroyuki Sumi, Shinji Shimizu, Yasuyuki Kakurai, Kenji Yoshikawa, Kensei Tobinai, Noriko Usui, Kiyohiko Hatake
International Journal of Clinical Oncology, 27, 1, 213, 223, Springer Science and Business Media LLC, 2021年10月01日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）,

Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor T-cell based anti-CD19 therapy. The ZUMA-1 study, multicenter, single-arm, registrational Phase 1/2 study of axi-cel demonstrated high objective response rate in patients with relapsed/refractory large B-cell lymphoma. Here, we present the results of the bridging study to evaluate the efficacy and safety of axi-cel in Japanese patients (JapicCTI-183914).




This study was the phase 2, multicenter, open-label, single-arm trial. Following leukapheresis, axi-cel manufacturing and lymphodepleting chemotherapy, patients received a single infusion of axi-cel (2.0 × 10⁶ cells/kg). Bridging therapy between leukapheresis and conditioning chemotherapy was not allowed. The primary endpoint was objective response rate.




Among 17 enrolled patients, 16 received axi-cel infusion. In the 15 efficacy evaluable patients, objective response rate was 86.7% (95% confidence interval: 59.5–98.3%); complete response/partial response were observed in 4 (26.7%)/9 (60.0%) patients, respectively. No dose-limiting toxicities were observed. Grade ≥ 3 treatment-emergent adverse events occurred in 16 (100%) patients—most commonly neutropenia (81.3%), lymphopenia (81.3%) and thrombocytopenia (62.5%). Cytokine release syndrome occurred in 13 (81.3%) patients (12 cases of grade 1 or 2 and 1 case of grade 4). No neurologic events occurred. Two patients died due to disease progression, but no treatment-related death was observed by the data-cutoff date (October 23, 2019).




The efficacy and safety of axi-cel was confirmed in Japanese patients with relapsed/refractory large B-cell lymphoma who have otherwise limited treatment options.




JapicCTI-183914.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report
Daniel Wolff, Vedran Radojcic, Robert Lafyatis, Resat Cinar, Rachel K. Rosenstein, Edward W. Cowen, Guang-Shing Cheng, Ajay Sheshadri, Anne Bergeron, Kirsten M. Williams, Jamie L. Todd, Takanori Teshima, Geoffrey D.E. Cuvelier, Ernst Holler, Shannon R. McCurdy, Robert R. Jenq, Alan M. Hanash, David Jacobsohn, Bianca D. Santomasso, Sandeep Jain, Yoko Ogawa, Philipp Steven, Zhonghui Katie Luo, Tina Dietrich-Ntoukas, Daniel Saban, Ervina Bilic, Olaf Penack, Linda M. Griffith, Meredith Cowden, Paul J. Martin, Hildegard T. Greinix, Stefanie Sarantopoulos, Gerard Socie, Bruce R. Blazar, Joseph Pidala, Carrie L. Kitko, Daniel R. Couriel, Corey Cutler, Kirk R. Schultz, Steven Z. Pavletic, Stephanie J. Lee, Sophie Paczesny
Transplantation and Cellular Therapy, 27, 10, 817, 835, Elsevier BV, 2021年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.

Off-the-shelf bone marrow-derived mesenchymal stem cell treatment for acute graft-versus-host disease: real-world evidence
Makoto Murata, Seitaro Terakura, Atsushi Wake, Kotaro Miyao, Kazuhiro Ikegame, Naoyuki Uchida, Keisuke Kataoka, Toshihiro Miyamoto, Makoto Onizuka, Tetsuya Eto, Noriko Doki, Shuichi Ota, Maho Sato, Yoshiko Hashii, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Atsuta, Shinichiro Okamoto, Takanori Teshima
Bone Marrow Transplantation, 56, 10, 2355, 2366, Springer Science and Business Media LLC, 2021年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Temcell is a cryopreserved, human bone marrow-derived mesenchymal stem cell (MSC) product approved for the treatment of patients of all ages with acute graft-versus-host disease (GVHD). Initial experience with Temcell in a real-world setting from a cellular therapy registry in Japan is presented. A total of 381 consecutive patients were enrolled since its approval in 2016. The median cell number infused was 2.00 × 106/kg. The most common number of infusions was 8 in 100 patients. Of the 306 evaluable patients, the overall response rate (ORR) on day 28 after the start of MSC therapy was 56%. Of the 151 evaluable patients who received it as second-line therapy following first-line steroid therapy for classic acute GVHD, the ORR was 61%. Liver involvement of GVHD and ≥14 days from first-line steroid therapy to second-line MSC therapy was associated with a lower ORR. Day 28 ORR, patient age, GVHD grade, GVHD organ involvement, and a number of GVHD therapies before MSC therapy were associated with nonrelapse mortality. Overall survival at 6 months in 381 patients was 40%. This study suggests that Temcell is one of the treatment options for steroid-refractory acute GVHD until a new treatment with survival benefit is developed.

Application of the proximal isovelocity surface area method for estimation of the effective orifice area in aortic stenosis
Masahiro Nakabachi, Hiroyuki Iwano, Michito Murayama, Hisao Nishino, Shinobu Yokoyama, Shingo Tsujinaga, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Kazunori Okada, Sanae Kaga, Mutsumi Nishida, Takanori Teshima, Toshihisa Anzai
Heart and Vessels, 37, 4, 638, 646, Springer Science and Business Media LLC, 2021年09月25日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Although the echocardiographic effective orifice area (EOA) calculated using the continuity equation is widely used for the assessment of severity in aortic stenosis (AS), the existence of high flow velocity at the left ventricular outflow tract (LVOT) potentially causes its overestimation. The proximal isovelocity surface area (PISA) method could be an alternative tool for the estimation of EOA that limits the influence of upstream flow velocity. EOA was calculated using the continuity equation (EOACont) and PISA method (EOAPISA), respectively, in 114 patients with at least moderate AS. The geometric orifice area (GOA) was also measured using the planimetry method in 51 patients who also underwent three-dimensional transesophageal echocardiography. Patients were divided into two groups according to the median LVOT flow velocity. EOAPISA could be obtained in 108 of the 114 patients (95%). Although there was a strong correlation between EOACont and EOAPISA (r = 0.78, P < 0.001), EOACont was statistically significantly larger than EOAPISA (0.86 ± 0.33 vs 0.75 ± 0.29 cm2, P < 0.001). Both EOACont and EOAPISA similarly correlated with GOA (r = 0.70, P < 0.001 and r = 0.77, P < 0.001, respectively). However, a fixed bias, which is hydrodynamically supposed to exist between EOA and GOA, was not observed between EOACont and GOA. In contrast, there was a negative fixed bias between EOAPISA and GOA with smaller EOAPISA than GOA. The difference between EOACont and GOA was significantly greater with a larger EOACont relative to GOA in patients with high LVOT flow velocity than in those without (0.16 ± 0.25 vs - 0.07 ± 0.10 cm2, P < 0.001). In contrast, the difference between EOAPISA and GOA was consistent regardless of the LVOT flow velocity (- 0.07 ± 0.12 vs - 0.07 ± 0.15 cm2, P = 0.936). The PISA method was applied to estimate EOA in patients with AS. EOAPISA could be an alternative parameter for AS severity grading in patients with high LVOT flow velocity in whom EOACont would potentially overestimate the orifice area.

Non-classical manifestations of acute GVHD
Robert Zeiser, Takanori Teshima
Blood, 138, 22, 2165, 2172, American Society of Hematology, 2021年09月05日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Acute graft-versus-host disease (GVHD) is a major life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). The classical target organs of acute GVHD include the intestines, liver, and skin. The damage of these organs is relatively easy to detect for the clinician as diarrhea, increased bilirubin, and rash. However, there is increasing evidence that also other organs, where the acute damage is less apparent or more difficult to distinguish from drug toxicity, such as the central nervous system, the lungs, the ovaries and testis, the thymus, the bone marrow and the kidney, can be target organs of acute GVHD. Here, we review current evidence for non-classical manifestations of acute GVHD in rodent models and in patients and discuss them in the context of novel emerging therapies for GVHD. A better understanding of the involvement of the non-classical GVHD target organs may help to improve patient outcomes after allo-HCT.

Graft-Versus-Host Disease Prophylaxis Using Low-Dose Antithymocyte Globulin in Peripheral Blood Stem Cell Transplantation—A Matched-Pair Analysis
Souichi Shiratori, Mio Kurata, Junichi Sugita, Shuichi Ota, Senji Kasahara, Jun Ishikawa, Kazunori Imada, Yasushi Onishi, Ken Ishiyama, Takashi Ashida, Yoshinobu Kanda, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Atsuta, Takanori Teshima
Transplantation and Cellular Therapy, 27, 12, 995.e1-995.e6, Elsevier BV, 2021年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Antithymocyte globulin (ATG) decreases chronic graft-versus-host disease (cGVHD) in peripheral blood stem cell transplantation (PBSCT); however, the optimal ATG dose has not been elucidated. We conducted a matched-pair analysis to evaluate whether low-dose ATG could inhibit cGVHD in HLA-matched PBSCT after myeloablative conditioning. A total of 70 patients who were enrolled in the JSCT-ATG15 study, a multicenter phase II clinical trial of 2 mg/kg of ATG (thymoglobulin) given on days -2 and -1, were compared with 210 patients not receiving ATG, who were matched for age, sex, disease, and calcineurin inhibitor selected from the database in Japan. The primary endpoint, cumulative incidence of extensive cGVHD at 2 years was significantly less in the ATG group than that in the non-ATG group (8.7% [95% CI, 3.5%-16.8%] versus 26.2% [95% CI, 20.3%-32.5%], P = .002). ATG significantly reduced the incidence of overall cGVHD and inhibited multiple organ involvement. The ATG group had favorable outcome compared to the non-ATG group in GVHD-free, and relapse-free survival at 2 years. In conclusion, low-dose ATG effectively inhibits chronic GVHD in PBSCT.

Phase II study of tazemetostat for relapsed or refractory B‐cell non‐Hodgkin lymphoma with EZH2 mutation in Japan
Koji Izutsu, Kiyoshi Ando, Momoko Nishikori, Hirohiko Shibayama, Takanori Teshima, Junya Kuroda, Koji Kato, Yoshitaka Imaizumi, Kisato Nosaka, Rika Sakai, Seiichiro Hojo, Tadashi Nakanishi, Shinya Rai
Cancer Science, 112, 9, 3627, 3635, Wiley, 2021年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Tazemetostat is a selective, reversible, small-molecule inhibitor of the histone methyltransferase enzyme, enhancer of zest homolog 2 (EZH2). In this multicenter, open-label, phase II study, we assessed the efficacy and safety of tazemetostat in Japanese patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma harboring the EZH2 mutation. Tazemetostat (800 mg twice daily) was given orally (28-day cycle) until disease progression or unacceptable toxicity. Among the 20 eligible patients, 17 were enrolled in cohort 1 (follicular lymphoma [FL]), and three were enrolled in cohort 2 (diffuse large B-cell lymphoma). At data cut-off, the objective response rate in cohort 1 was 76.5%, including six patients (35.3%) with complete response and seven patients (41.2%) with partial response (PR). All three patients in cohort 2 achieved PR. In cohort 1, median progression-free survival (PFS) was not reached at the median follow-up of 12.9 months. The estimated PFS rate at 12 and 15 months was 94.1% and 73.2%, respectively. The most common grade 3 treatment-emergent adverse event (TEAE) was lymphopenia (n = 2). Grade 4 TEAEs included hypertriglyceridemia and pneumonia aspiration (n = 1 each), which were not related to tazemetostat. Treatment-emergent adverse events leading to study drug discontinuation were reported in four of the 20 patients, indicating that the safety profile of tazemetostat was acceptable and manageable. Tazemetostat 800 mg twice daily showed encouraging efficacy in patients with R/R EZH2 mutation-positive FL with a manageable safety profile in the overall population. Thus, tazemetostat could be a potential treatment for R/R EZH2 mutation-positive FL.

Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors
Souichi Shiratori, Junichi Sugita, Shigeo Fuji, Jun Aoki, Masashi Sawa, Yukiyasu Ozawa, Daigo Hashimoto, Ken-ichi Matsuoka, Kazunori Imada, Noriko Doki, Takashi Ashida, Yasunori Ueda, Masatsugu Tanaka, Yasushi Sawayama, Tatsuo Ichinohe, Seitaro Terakura, Satoko Morishima, Yoshiko Atsuta, Takahiro Fukuda, Takanori Teshima
Bone Marrow Transplantation, 56, 9, 2231, 2240, Springer Science and Business Media LLC, 2021年09月, ［査読有り］
研究論文（学術雑誌）

Logistic advantage of two-step screening strategy for SARS-CoV-2 at airport quarantine
Isao Yokota, Peter Y. Shane, Takanori Teshima
Travel Medicine and Infectious Disease, 43, 102127, 102127, Elsevier BV, 2021年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Airport quarantine is required to reduce the risk of entry of travelers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is challenging for both high accuracy and rapid turn-around time to coexist in testing; polymerase chain reaction (PCR) is time-consuming with high accuracy, while antigen testing is rapid with less accuracy. However, there are few data on the concordance between PCR and antigen testing. METHODS: Arrivals at three international airports in Japan between July 29 and September 30, 2020 were tested for SARS-CoV-2 using self-collected saliva by a screening strategy with initial chemiluminescent enzyme immunoassay (CLEIA) followed by confirmatory nucleic acid amplification tests (NAAT) only for intermediate range antigen concentrations. RESULTS: Among the 95,457 persons entering Japan during the period, 88,924 (93.2%) were tested by CLEIA, and 0.29% (254/88,924) were found to be SARS-CoV-2 antigen positive (≥4.0 pg/mL). NAAT was required for confirmatory testing in 0.58% (513/88,924) with intermediate antigen concentrations (0.67-4.0 pg/mL) whereby the virus was detected in 6.6% (34/513). This two-step strategy reduced the utilization of NAAT to one out of every 173 test subjects. The estimated performance of this strategy did not show significant increase in false negatives as compared to performing NAAT in all subjects. CONCLUSIONS: Point of care testing by quantitative CLEIA using self-collected saliva is less labor-intensive and yields results rapidly, thus suitable as an initial screening test. Reserving NAAT for CLEIA indeterminate cases may prevent compromising accuracy while significantly improving the logistics of administering mass-screening at large venues.

Relevance of early-diastolic mitral regurgitation in dilated heart
Asuka Tanemura, Michito Murayama, Hiroyuki Iwano, Yasuyuki Chiba, Mutsumi Nishida, Takanori Teshima, Toshihisa Anzai
Journal of Echocardiography, 21, 1, 50, 52, Springer Science and Business Media LLC, 2021年08月30日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）

Performance of Qualitative and Quantitative Antigen Tests for SARS-CoV-2 Using Saliva
Isao Yokota, Takayo Sakurazawa, Junichi Sugita, Sumio Iwasaki, Keiko Yasuda, Naoki Yamashita, Shinichi Fujisawa, Mutsumi Nishida, Satoshi Konno, Takanori Teshima
Infectious Disease Reports, 13, 3, 742, 747, MDPI AG, 2021年08月24日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The rapid detection of SARS-CoV-2 is critical for the prevention of disease outbreaks. Antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) can yield results more quickly than PCR. We evaluated the performance of ICA and CLEIA using 34 frozen PCR-positive (17 saliva samples and 17 nasopharyngeal swabs [NPS]) and 309 PCR-negative samples. ICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity rates of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with a positivity of 82% in saliva and 100% in NPS. These results suggest that the use of ICA should be limited to an earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.

The Pathophysiology and Treatment of Graft-Versus-Host Disease: Lessons Learnt From Animal Models
Takanori Teshima, Geoffrey R. Hill
Frontiers in Immunology, 12, 715424, 715424, Frontiers Media SA, 2021年08月19日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for hematologic malignancies, bone marrow failure syndromes, and inherited immunodeficiencies and metabolic diseases. Graft-versus-host disease (GVHD) is the major life-threatening complication after allogeneic HCT. New insights into the pathophysiology of GVHD garnered from our understanding of the immunological pathways within animal models have been pivotal in driving new therapeutic paradigms in the clinic. Successful clinical translations include histocompatibility matching, GVHD prophylaxis using cyclosporine and methotrexate, posttransplant cyclophosphamide, and the use of broad kinase inhibitors that inhibit cytokine signaling (e.g. ruxolitinib). New approaches focus on naïve T cell depletion, targeted cytokine modulation and the inhibition of co-stimulation. This review highlights the use of animal transplantation models to guide new therapeutic principles.

Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products
Makoto Murata, Takanori Teshima
Frontiers in Immunology, 12, 724380, 724380, Frontiers Media SA, 2021年08月19日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Acute graft-versus-host disease (GVHD) is a life-threatening complication that can develop after allogeneic hematopoietic stem cell transplantation. In particular, the prognosis of patients with steroid-refractory acute GVHD is extremely poor. Ryoncil™ (remestemcel-L), a human bone marrow-derived mesenchymal stem cell (MSC) product, failed to show superiority over placebo in patients with steroid-refractory acute GVHD, but it was approved for use in pediatric patients in Canada and New Zealand based on the results of a subgroup analysis. Temcell^®, an equivalent manufactured MSC product to remestemcel-L, was approved in Japan based on small single-arm studies by using a regulation for regenerative medicine in 2016. The efficacy of Temcell was evaluated in 381 consecutive patients treated with Temcell during the initial 3 years after its approval. Interestingly, its real-world efficacy was found to be equivalent to that observed in a prospective study of remestemcel-L with strict eligibility criteria. In this article, the potential of MSC therapy in the treatment of acute GVHD is discussed. A meticulous comparison of studies of remestemcel-L and Temcell, remestemcel-L/Temcell and ruxolitinib, and remestemcel-L/Temcell and thymoglobulin showed that the precise position of remestemcel-L/Temcell therapy in the treatment of acute GVHD remains to be determined.

Graft-versus-host disease: a disorder of tissue regeneration and repair
Ronjon Chakraverty, Takanori Teshima
Blood, 138, 18, 1657, 1665, American Society of Hematology, 2021年08月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Regenerative failure at barrier surfaces and maladaptive repair leading to fibrosis are hallmarks of graft-versus-host disease (GVHD). Although immunosuppressive treatment can control inflammation, impaired tissue homeostasis leads to prolonged organ damage and impaired quality of life. In this Spotlight article, we review recent research that addresses the critical failures in tissue regeneration and repair that underpin treatment-resistant GVHD. We highlight current interventions designed to overcome these defects and provide our assessment of the future therapeutic landscape.

Patients with marginal zone dural lymphoma successfully treated with rituximab and bendamustine: A report of two cases
Yutaka Tsutsumi, Shinichi Ito, Jun Nagai, Takahiro Tateno, Takanori Teshima
Molecular and Clinical Oncology, 15, 4, 208, 208, Spandidos Publications, 2021年08月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Primary dural low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a rare disease whose main treatment has been local surgery or radiotherapy. Until now, there have been no cases of dural MALT lymphoma treatment of a patient with several relapses or systemic disease. The present study included two patients with dural MALT lymphoma who had several relapses or systemic disease. Since local therapy was not enough to control the disease for these patients, they were treated with systemic chemotherapy. The patients were administered rituximab (375 mg/m2) and two days of bendamustine (90 mg/m2). Both patients recovered from their clinical symptoms immediately, and their tumors were reduced. During and after rituximab and bendamustine therapy, no central nervous system (CNS) metastasis or cerebrospinal fluid invasion of MALT were observed. The current approach using rituximab and bendamustine treatment was effective against dural MALT lymphoma and may prevent its invasion of the CNS.

Mass Screening of Asymptomatic Persons for Severe Acute Respiratory Syndrome Coronavirus 2 Using Saliva
Isao Yokota, Peter Y Shane, Kazufumi Okada, Yoko Unoki, Yichi Yang, Tasuku Inao, Kentaro Sakamaki, Sumio Iwasaki, Kasumi Hayasaka, Junichi Sugita, Mutsumi Nishida, Shinichi Fujisawa, Takanori Teshima
Clinical Infectious Diseases, 73, 3, e559, e565, Oxford University Press (OUP), 2021年08月02日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）,


Coronavirus disease 2019 (COVID-19) has rapidly evolved to become a global pandemic, largely owing to the transmission of its causative virus through asymptomatic carriers. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of polymerase chain reaction testing. In addition, although self-collected saliva samples have significant logistical advantages in mass screening, their utility as an alternative specimen in asymptomatic persons is yet to be determined.





We conducted a mass screening study to compare the utility of nucleic acid amplification, such as reverse-transcription polymerase chain reaction testing, using nasopharyngeal swab (NPS) and saliva samples from each individual in 2 cohorts of asymptomatic persons: the contact-tracing cohort and the airport quarantine cohort.





In this mass screening study including 1924 individuals, the sensitivities of nucleic acid amplification testing with NPS and saliva specimens were 86% (90% credible interval, 77%–93%) and 92% (83%–97%), respectively, with specificities &gt;99.9%. The true concordance probability between the NPS and saliva tests was estimated at 0.998 (90% credible interval, .996–.999) given the recent airport prevalence of 0.3%. In individuals testing positive, viral load was highly correlated between NPS and saliva specimens.





Both NPS and saliva specimens had high sensitivity and specificity. Self-collected saliva specimens are valuable for detecting SARS-CoV-2 in mass screening of asymptomatic persons.

Clinical outcomes of intervention for carbapenems and anti-methicillin-resistant Staphylococcus aureus antibiotics by an antimicrobial stewardship team
Keisuke Kagami, Nobuhisa Ishiguro, Takehiro Yamada, Yusuke Niinuma, Sumio Iwasaki, Keisuke Taki, Tatsuya Fukumoto, Kasumi Hayasaka, Mutsumi Nishida, Junichi Sugita, Takanori Teshima, Mitsuru Sugawara, Yoh Takekuma
American Journal of Infection Control, 49, 12, 1493, 1498, Elsevier BV, 2021年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There are no reports on the effects of interventions, such as discontinuation and change and/or de-escalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. METHODS: This retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. RESULTS: Favorable clinical responses were obtained in 165 of 184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P = .056). All-cause 30 day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P = .045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P = .026 for carbapenem; 10 days [5.3-15] vs 15.5 days [13.8-45.3], respectively, P = .014 for anti-MRSA antibiotic). CONCLUSIONS: This is the first study to investigate the effects of interventions such as discontinuation and change and/ or de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes.

A novel strategy for SARS-CoV-2 mass screening with quantitative antigen testing of saliva: a diagnostic accuracy study
Isao Yokota, Peter Y Shane, Kazufumi Okada, Yoko Unoki, Yichi Yang, Sumio Iwasaki, Shinichi Fujisawa, Mutsumi Nishida, Takanori Teshima
The Lancet Microbe, 2, 8, e397, e404, Elsevier BV, 2021年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Quantitative RT-PCR (RT-qPCR) of nasopharyngeal swab (NPS) samples for SARS-CoV-2 detection requires medical personnel and is time consuming, and thus is poorly suited to mass screening. In June, 2020, a chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. In this study, we assessed the utility of CLEIA in mass SARS-CoV-2 screening. Methods: We did a diagnostic accuracy study to develop a mass-screening strategy for salivary detection of SARS-CoV-2 by CLEIA, enrolling hospitalised patients with clinically confirmed COVID-19, close contacts identified at community health centres, and asymptomatic international arrivals at two airports, all based in Japan. All test participants were enrolled consecutively. We assessed the diagnostic accuracy of CLEIA compared with RT-qPCR, estimated according to concordance (Kendall's coefficient of concordance, W), and sensitivity (probability of CLEIA positivity given RT-qPCR positivity) and specificity (probability of CLEIA negativity given RT-qPCR negativity) for different antigen concentration cutoffs (0·19 pg/mL, 0·67 pg/mL, and 4·00 pg/mL; with samples considered positive if the antigen concentration was equal to or more than the cutoff and negative if it was less than the cutoff). We also assessed a two-step testing strategy post hoc with CLEIA as an initial test, using separate antigen cutoff values for test negativity and positivity from the predefined cutoff values. The proportion of intermediate results requiring secondary RT-qPCR was then quantified assuming prevalence values of RT-qPCR positivity in the overall tested population of 10%, 30%, and 50%. Findings: Self-collected saliva was obtained from 2056 participants between June 12 and Aug 6, 2020. Results of CLEIA and RT-qPCR were concordant in 2020 (98·2%) samples (Kendall's W=0·99). Test sensitivity was 85·4% (76 of 89 positive samples; 90% credible interval [CrI] 78·0-90·3) at the cutoff of 0·19 pg/mL; 76·4% (68 of 89; 68·2-82·8) at the cutoff of 0·67 pg/mL; and 52·8% (47 of 89; 44·1-61·3) at the cutoff of 4·0 pg/mL. Test specificity was 91·3% (1796 of 1967 negative samples; 90% CrI 90·2-92·3) at the cutoff of 0·19 pg/mL, 99·2% (1952 of 1967; 98·8-99·5) at the cutoff of 0·67 pg/mL, and 100·0% (1967 of 1967; 99·8-100·0) at the cutoff of 4·00 pg/mL. Using a two-step testing strategy with a CLEIA negativity cutoff of 0·19 pg/mL (to maximise sensitivity) and a CLEIA positivity cutoff of 4·00 pg/mL (to maximise specificity), the proportions of indeterminate results (ie, samples requiring secondary RT-qPCR) would be approximately 11% assuming a prevalence of RT-qPCR positivity of 10%, 16% assuming a prevalence of RT-qPCR positivity of 30%, and 21% assuming a prevalence of RT-qPCR positivity of 50%. Interpretation: CLEIA testing of self-collected saliva is simple and provides results quickly, and is thus suitable for mass testing. To improve accuracy, we propose a two-step screening strategy with an initial CLEIA test followed by confirmatory RT-qPCR for intermediate concentrations, varying positive and negative thresholds depending on local prevalence. Implementation of this strategy has expedited sample processing at Japanese airports since July, 2020, and might apply to other large-scale mass screening initiatives. Funding: Ministry of Health, Labour and Welfare, Japan.

Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease
Robert Zeiser, Nicola Polverelli, Ron Ram, Shahrukh K. Hashmi, Ronjon Chakraverty, Jan Moritz Middeke, Maurizio Musso, Sebastian Giebel, Ant Uzay, Peter Langmuir, Norbert Hollaender, Maanasa Gowda, Tommaso Stefanelli, Stephanie J. Lee, Takanori Teshima, Franco Locatelli
New England Journal of Medicine, 385, 3, 228, 238, Massachusetts Medical Society, 2021年07月15日, ［査読有り］
研究論文（学術雑誌）

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

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

A case of immune checkpoint inhibitor-associated gastroenteritis detected by ultrasonography.
Satomi Omotehara, Mutsumi Nishida, Kana Yamanashi, Kensuke Sakurai, Takehiko Katsurada, Yoshito Komatsu, Ai Shimizu, Hitoshi Shibuya, Naofumi Shinagawa, Junichi Sugita, Takanori Teshima
Journal of clinical ultrasound : JCU, 49, 6, 605, 609, 2021年07月, ［国際誌］
英語, While immune checkpoint inhibitors (ICIs) have antitumor effects, they also have characteristic side effects, including colitis. However, gastritis has rarely been reported. We report a case of a patient with lung adenocarcinoma who presented with epigastric pain and diarrhea following pembrolizumab administration. Sonography of the abdomen demonstrated diffuse, although mild, gastric wall thickening (mainly in the submucosa), as well as a slight decrease in echogenicity throughout the gastric wall. While the mucosal surface was relatively smooth, color Doppler examination showed increased vascularity. Esophagogastroduodenoscopy and pathological examination confirmed the diagnosis of ICI-related gastroenteritis.

Effect of varying storage conditions on diagnostic test outcomes of SARS-CoV-2
Satoshi Oguri, Shinichi Fujisawa, Keisuke Kamada, Sho Nakakubo, Yu Yamashita, Junichi Nakamura, Hiroshi Horii, Kazuki Sato, Mutsumi Nishida, Takanori Teshima, Yoichi Ohiro, Ayato Takada, Satoshi Konno
Journal of Infection, 83, 1, 119, 145, Elsevier BV, 2021年07月, ［査読有り］
研究論文（学術雑誌）

Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation
Mutsumi Nishida, Junichi Sugita, Shuichiro Takahashi, Takahito Iwai, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Ryosuke Sakano, Hitoshi Shibuya, Isao Yokota, Akihiro Iguchi, Takanori Teshima
International Journal of Hematology, 114, 1, 94, 101, Springer Science and Business Media LLC, 2021年07月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

Platelet decrease and efficacy of platelet‐rich plasma return following peripheral blood stem cell apheresis
Takahiro Shima, Teppei Sakoda, Tomoko Henzan, Yuya Kunisaki, Takeshi Sugio, Kenjiro Kamezaki, Hiromi Iwasaki, Takanori Teshima, Takahiro Maeda, Koichi Akashi, Toshihiro Miyamoto
Journal of Clinical Apheresis, 36, 5, 687, 696, Wiley, 2021年06月16日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and is widely performed in clinical practice. Platelet loss is one of the major complications of PBSC apheresis, and platelet-rich plasma (PRP) return is considered in case of platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss and the efficacy of PRP return postapheresis. METHODS: We assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated the efficacy of PRP transfusion on platelet recovery postapheresis. RESULTS: In both allo- and auto-PBSC settings, the preapheresis platelet count (range, 84-385 and 33-558 × 109 /L, respectively) decreased postapheresis (range, 57-292 and 20-429 × 109 /L, respectively), whereas severe platelet decrease (<50 × 109 /L) was only observed in auto-PBSC patients (n = 9). We confirmed that platelet count before apheresis was a risk factor for severe platelet decrease (<50 × 109 /L) following auto-PBSC apheresis (odds ratio 0.749, P < .049). PRP return postapheresis facilitated platelet recovery in more than 80% of cases in both allo and auto settings. CONCLUSION: Lower platelet count preapheresis is a useful predictor of severe platelet decrease following auto-PBSC apheresis and PRP return is an effective process to facilitate platelet recovery postapheresis.

Cost Effectiveness Analysis of Tisagenlecleucel for the Treatment of Adult Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma in Japan
Shiho Wakase, Takanori Teshima, Jie Zhang, Qiufei Ma, Taizo Fujita, Hongbo Yang, Xinglei Chai, Cynthia Z. Qi, Qing Liu, Eric Q. Wu, Ataru Igarashi
Transplantation and Cellular Therapy, 27, 6, 506.e1, 506.e10, Elsevier BV, 2021年06月, ［査読有り］
英語, 研究論文（学術雑誌）, There are limited treatment options and substantial unmet needs for adult patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) in Japan. In 2019, tisagenlecleucel, a CD19-directed chimeric antigen receptor T cell therapy, was approved for r/r DLBCL in Japan. The efficacy and safety of tisagenlecleucel were demonstrated in the pivotal phase II single-arm JULIET trial. The objective of the current study was to assess the cost-effectiveness of tisagenlecleucel treatment strategy versus current standard of care (salvage chemotherapy treatment strategy) for the treatment of patients with r/r DLBCL in Japan. A three-state partitioned survival model was constructed from a Japanese public healthcare payer's perspective, with the following three health states: progression-free survival, progressive/relapsed disease, and death. Because the tisagenlecleucel arm included patients who did or did not receive the infusion, a decision-tree structure was used to partition patients based on their infusion status. Treatment efficacy and costs were based on tisagenlecleucel-infused patients for those who received the infusion; for non-infused patients, they were based on standard salvage chemotherapy. The efficacy inputs for tisagenlecleucel-infused patients and salvage chemotherapy were based on observed data in the JULIET trial and the international SCHOLAR-1 meta-analysis, respectively, before year 3. Afterward, all patients were assumed to have no further progression and to incur the mortality risk of long-term DLBCL survivors. The base case analysis explored a lifetime horizon (44 years), with costs and effectiveness discounted 2.0% annually, and it used a monthly model cycle. Direct costs were considered in the base case, composed of pretreatment costs, treatment costs, adverse events management costs, follow-up costs before progression, subsequent SCT costs, post-progression costs, and terminal care costs. Total incremental costs, life years (LYs), and quality-adjusted life years (QALYs) were compared for tisagenlecleucel versus salvage chemotherapy. The incremental cost-effectiveness ratio (ICER) was estimated as the costs per QALY gained, and a threshold of \7.5 million was used to assess whether tisagenlecleucel is cost effective. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel and salvage chemotherapy were 7.24 and 4.35 years, respectively; the corresponding QALYs were 5.42 and 2.57 years, respectively. The discounted incremental LYs and QALYs comparing tisagenlecleucel to salvage chemotherapy were estimated as 2.89 and 2.85 years, respectively. Over a lifetime horizon, the model estimated that tisagenlecleucel had a total incremental cost of \15,590,335 (discounted) versus salvage chemotherapy. Tisagenlecleucel was associated with an ICER of \5,476,496 per QALY gained compared to salvage chemotherapy. Extensive sensitivity analyses supported the base-case findings. Tisagenlecleucel is a cost-effective treatment strategy for r/r DLBCL compared to salvage chemotherapy treatment strategy from a Japanese public healthcare payer's perspective.

High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease
Souichi Shiratori, Hiroyuki Ohigashi, Takahide Ara, Atsushi Yasumoto, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
Annals of Hematology, 100, 5, 1321, 1328, Springer Science and Business Media LLC, 2021年05月, ［査読有り］
研究論文（学術雑誌）

音響特性を考慮した乳腺病変の最適な超音波画像撮像条件の検討　　　　　　　　　　　　　　　
岩井 孝仁, 工藤 悠輔, 西田 睦, 畑瀬 理恵, 表原 里実, 大栗 拓真, 嵯峨 早友佳, 神山 直久, 杉田 純一, 豊嶋 崇徳
超音波医学, 48, Suppl., S790, S790, (公社)日本超音波医学会, 2021年04月
日本語

Learning to mellow out GVHD.
Takanori Teshima
Blood, 137, 9, 1142, 1143, 2021年03月04日, ［国際誌］
英語, 研究論文（学術雑誌）

Extramedullary hematopoiesis of the cranial dura.
Keito Suto, Junichi Sugita, Daigo Hashimoto, Hiroyuki Kameda, Tomoko Mitsuhashi, Takanori Teshima
International journal of hematology, 113, 3, 315, 317, 2021年03月, ［国内誌］
英語

Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Pediatric and Young Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia in Japan
Shiho Wakase, Takanori Teshima, Jie Zhang, Qiufei Ma, Yoko Watanabe, Hongbo Yang, Cynthia Z. Qi, Xinglei Chai, Yanwen Xie, Eric Q. Wu, Ataru Igarashi
Transplantation and Cellular Therapy, 27, 3, 241.e1, 241.e11, Elsevier BV, 2021年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Until recently, treatment options were relatively limited for children and young adults with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL). Tisagenlecleucel is a chimeric antigen receptor T cell (CAR-T) immunotherapy with promising efficacy and manageable safety that was approved in Japan in 2019 for the treatment of CD19-positive r/r B cell ALL (B-ALL). However, there is no publication assessing the cost-effectiveness of CAR-T in Japan. The objective of this study was to assess the cost-effectiveness of a tisagenlecleucel treatment strategy compared to a blinatumomab treatment strategy and a clofarabine combination treatment strategy (i.e., clofarabine + cyclophosphamide + etoposide) in Japan for pediatric and young adult patients up to 25 years of age with r/r B-ALL. A partitioned survival model with a lifetime horizon and monthly cycle was constructed from a Japanese public healthcare payer's perspective. Patients were distributed across the following partitioned health states: event-free survival (EFS), progressive disease, and death, which were informed by the EFS and overall survival (OS) data of respective clinical trials before year 5. For the tisagenlecleucel arm, a decision-tree structure was used to partition patients based on the infusion status; those who discontinued prior to receiving infusion were assigned efficacy and cost inputs of blinatumomab and those who received infusion were assigned efficacy and costs inputs based on tisagenlecleucel-infused patients. As trial data for blinatumomab and clofarabine ended before year 5, matching-adjusted indirect comparisons were used to extrapolate OS between the end of trial observation and up to year 5. All surviving patients followed the mortality risk of long-term ALL survivors without additional risk of disease relapse after year 5, regardless of initial treatment strategies. The model accounted for pretreatment costs, treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation costs, and terminal care costs. Incremental cost-effectiveness ratios (ICERs) per life-years (LYs) gained and ICERs per quality-adjusted life-years (QALYs) gained were evaluated using a 2% discount rate, and a threshold of \7.5 million was used to assess cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel, blinatumomab, and clofarabine combination treatment strategies were 13.3, 4.0, and 2.7 years, respectively; the corresponding QALYs were 11.6, 3.1, and 2.1 years, respectively. The ICERs per QALY gained for tisagenlecleucel were \2,035,071 versus blinatumomab and \2,644,702 versus clofarabine combination therapy. Extensive sensitivity analyses supported the findings. Tisagenlecleucel is a cost-effective treatment strategy for pediatric and young adult patients with r/r B-ALL from a Japanese public healthcare payer's perspective.

A multicenter phase II study of intrabone single-unit cord blood transplantation without antithymocyte globulin
Tetsuya Nishida, Takeshi Kobayashi, Masashi Sawa, Shinichi Masuda, Yasuhiko Shibasaki, Tatsunori Goto, Noriko Fukuhara, Nobuharu Fujii, Kazuhiro Ikegame, Junichi Sugita, Takashi Ikeda, Yachiyo Kuwatsuka, Ritsuro Suzuki, Yuho Najima, Noriko Doki, Tomonori Kato, Yuichiro Inagaki, Yoshikazu Utsu, Nobuyuki Aotsuka, Masayoshi Masuko, Seitaro Terakura, Yasushi Onishi, Yoshinobu Maeda, Masaya Okada, Takanori Teshima, Makoto Murata
Annals of Hematology, 100, 3, 743, 752, Springer Science and Business Media LLC, 2021年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 107/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 109/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.

Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli
Keisuke Kagami, Nobuhisa Ishiguro, Takehiro Yamada, Yusuke Niinuma, Sumio Iwasaki, Keisuke Taki, Tatsuya Fukumoto, Kasumi Hayasaka, Reiko Oyamada, Tsubasa Watanabe, Mutsumi Nishida, Junichi Sugita, Takanori Teshima, Mitsuru Sugawara, Yoh Takekuma
Journal of Infection and Chemotherapy, 27, 3, 473, 479, Elsevier BV, 2021年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli have been poorly investigated in Japanese patients. This study was performed to investigate the efficacy and safety of colistin in Japanese patients by analyzing a considerable number of cases. Furthermore, we evaluated the relationship between the plasma concentration and efficacy and safety of colistin in some cases. METHODS: A retrospective cohort study was conducted at Hokkaido University Hospital, analyzing patients treated with colistin (colistimethate sodium) during the period from January 2007 to December 2019. RESULTS: Overall, 42 cases were enrolled. Favorable clinical response was observed in 25 cases (59.5%), with an all-cause 30-day mortality of 33.3% (14/42 cases). Microbiological eradication was achieved in 18 cases (42.9%). Nephrotoxicity was observed in 20 cases (47.6%) and was mild and reversible in all cases. Plasma trough concentrations of colistin determined in nine patients correlated with changes in serum creatinine concentration (⊿) and creatinine clearance (%). The cutoff value of colistin trough concentration for nephrotoxicity was 2.02 μg/mL. CONCLUSION: Our results showed approximately 60% clinical efficacy of colistin therapy against infections caused by multidrug-resistant gram-negative bacilli in the patients. Further studies with larger populations are needed to elucidate the efficacy and safety of colistin in Japanese patients.

Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation
Junichi Sugita, Tomohiko Kamimura, Takayuki Ishikawa, Shuichi Ota, Tetsuya Eto, Takashi Kuroha, Yasuhiko Miyazaki, Hiroaki Kumagai, Keitaro Matsuo, Koichi Akashi, Shuichi Taniguchi, Mine Harada, Takanori Teshima
Bone Marrow Transplantation, 56, 3, 596, 604, Springer Science and Business Media LLC, 2021年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II-IV acute GVHD, III-IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC.

Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia
Seitaro Terakura, Yachiyo Kuwatsuka, Junichi Sugita, Satoshi Takahashi, Yukiyasu Ozawa, Kazutaka Ozeki, Satoshi Yoshioka, Hirohisa Nakamae, Toshiro Kawakita, Masashi Sawa, Satoshi Morishige, Yuho Najima, Yuna Katsuoka, Emiko Sakaida, Yasuji Kouzai, Takafumi Kimura, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Atsuta, Makoto Murata, Takanori Teshima
International Journal of Hematology, 113, 6, 840, 850, Springer Science and Business Media LLC, 2021年02月21日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, To investigate the association between methotrexate (MTX) dosage and engraftment, graft-versus-host disease (GVHD) incidence, and survival in umbilical cord blood transplantation (UCBT), we compared transplant outcomes after UCBT with various GVHD prophylaxis regimens, using registry data with additional data collection. Patients transplanted for acute myeloid leukemia with a calcineurin inhibitor (CNI) and either MTX or mycophenolate mofetil (MMF) combination were selected. In total, 888 single-unit UCBTs (MTX15-10-10, 415; MTX10-7-7, 294; MTX5-5-5, 71; MMF, 108) were included. In multivariate analyses with MTX15-10-10 as the reference, the likelihood of neutrophil and platelet engraftment was significantly worse in the MTX10-7-7 group, and similarly better in MMF group compared with MTX15-10-10. All variables including CyA vs Tac and 4-group GVHD prophylaxis became significant for the risk of grade II-IV acute GVHD in the final multivariate model. We observed significant additional effects of combined MTX dose in the Tac group, which were larger with lower MTX dose and MMF. No significant difference was observed in survival risk among GVHD prophylaxis groups. Despite the potential background differences in the combined CNI and conditioning regimen, we conclude that the recommended GVHD prophylaxis is a combination of CyA plus MTX15-10-10 or Tac plus MMF.

Factors for the Variability of Three Acceptable Maximal Expiratory Flow–Volume Curves in Chronic Obstructive Pulmonary Disease
Masafumi Yamamoto, Satoshi Konno, Hironi Makita, Katsuaki Nitta, Kaoruko Shimizu, Masaru Suzuki, Mutsumi Nishida, Junichi Sugita, Takanori Teshima, Masaharu Nishimura
International Journal of Chronic Obstructive Pulmonary Disease, Volume 16, 415, 422, Informa UK Limited, 2021年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Generally, the maximal expiratory flow-volume (MEFV) curve must be measured for the diagnosis and staging of chronic obstructive pulmonary disease (COPD). As this test is effort dependent, international guidelines recommend that three acceptable trials are required for each test. However, no study has examined the magnitude and factors for the variability in parameters among three acceptable trials. Methods: We evaluated the intra-individual variations in several parameters among three acceptable MEFV curves obtained at one-time point in patients with COPD (n = 28, stage 1; n = 36, stage 2; n = 21, stages 3-4). Next, the factors for such variations were examined using forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Results: The averages of coefficient of variation (CV) for FEV1 and FVC were 2.0% (range: 1.0-3.0%) and 1.6% (0.9-2.2%), respectively. Both parameters were significantly better than peak expiratory flow rate, forced expiratory flow at 50% of expired FVC, and forced expiratory flow at 75% of expired FVC (CVs: 5.0-6.9%). A higher spirometric stage was significantly associated with higher CVs for FVC and FEV1, and older age was significantly correlated with a higher variation in FEV1 alone. Furthermore, a significantly inverse association was observed between emphysema severity, and the CVs for FEV1, but not that for FVC, regardless of spirometric stage. Conclusion: Both FVC and FEV1 are highly reproducible; nevertheless, older age, lower FEV1 at baseline, and non-emphysema phenotype are factors for a higher variability in FEV1 in patients with COPD.

SARS-CoV-2 detection by fluorescence loop-mediated isothermal amplification with and without RNA extraction
Keisuke Taki, Isao Yokota, Tatsuya Fukumoto, Sumio Iwasaki, Shinichi Fujisawa, Masayoshi Takahashi, Saeki Negishi, Kasumi Hayasaka, Kaori Sato, Satoshi Oguri, Mutsumi Nishida, Junichi Sugita, Satoshi Konno, Tomoya Saito, Takanori Teshima
Journal of Infection and Chemotherapy, 27, 2, 410, 412, Elsevier BV, 2021年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Rapid and simple point-of-care detection of SARS-CoV-2 is an urgent need to prevent pandemic. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) can detect SARS-CoV-2 more rapidly than RT-PCR. Saliva is non-invasive specimen suitable for mass-screening, but data comparing utility of nasopharyngeal swab (NPS) and saliva in RT-LAMP test are lacking and it remains unclear whether SARS-CoV-2 could be detected by direct processing of samples without the need for prior RNA extraction saliva. In this study, we compared utility of saliva and NPS samples for the detection of SARS-CoV-2 by a novel RT-fluorescence LAMP (RT-fLAMP). The sensitivity and specificity of the RT-fLAMP with RNA extraction were 97% and 100%, respectively, with equivalent utility of NPS and saliva. However, sensitivity was decreased to 71% and 47% in NPS and saliva samples without RNA extraction, respectively, suggesting that RNA extraction process may be critical for the virus detection by RT-fLAMP.

Medical database analysis of japanese multiple myeloma patients with planned stem cell transplantation (MEDALIST) – a focus on healthcare resource utilization and cost
Shinsuke Iida, Tadao Ishida, Katsuhisa Horimoto, Hirotaka Kazama, Hyunchung Kim, Bruce Crawford, Takanori Teshima
International Journal of Hematology, 113, 2, 271, 278, Springer Science and Business Media LLC, 2021年02月, ［査読有り］
研究論文（学術雑誌）

[Emergence of mutation in the colony-stimulating factor 3 receptor gene during follow-up of unclassifiable myeloproliferative neoplasm].
Shinpei Harada, Kohei Okada, Shota Yokoyama, Daisuke Hidaka, Eiko Hayase, Masahiro Onozawa, Hideki Goto, Daigo Hashimoto, Kaoru Kahata, Tomoyuki Endo, Takanori Teshima
[Rinsho ketsueki] The Japanese journal of clinical hematology, 62, 11, 1609, 1614, 2021年, ［国内誌］
日本語, 研究論文（学術雑誌）, A 25-year-old male with a medical history of stress polycythemia was admitted to a previous hospital for leukocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed left-shifted myeloid hyperplasia without increased blasts and normal male karyotype. No mutations of JAK2, V617F, and colony-stimulating factor 3 receptor gene (CSF3R) were detected. Fluorescence in-situ hybridization for BCR-ABL1 and FIP1L1-PDGFRA were negative. Based on these findings, a diagnosis of an unclassifiable myeloproliferative neoplasm was made, and he was started on hydroxyurea treatment. He was referred to our hospital in April 2016 for transfusion dependence. Bone marrow examination performed at our hospital revealed granulocytic dysplasia and CSF3R T618I was detected. After induction therapy, CSF3R T618I became undetectable, and he went on to undergo allogeneic stem cell transplantation in October 2016. He has been in remission for >4 years posttransplantation. CSF3R T618I is one of the genes responsible for chronic neutrophilic leukemia and atypical chronic myeloid leukemia, suggesting its involvement in the pathogenesis of this case.

心内圧波形に基づく拡張早期僧帽弁逆流の発生機序に関する考察
種村 明日香, 村山 迪史, 岩野 弘幸, 西野 久雄, 横山 しのぶ, 中鉢 雅大, 本居 昂, 辻永 真吾, 岡田 一範, 加賀 早苗, 西田 睦, 豊嶋 崇徳
超音波検査技術抄録集, 46, S132, S132, 一般社団法人 日本超音波検査学会, 2021年
日本語

Two cases of chronic obstructive pulmonary disease with undetectable diffusing capacity for carbon monoxide.
Ayumi Ohara, Satoshi Konno, Kaoruko Shimizu, Masaru Suzuki, Masafumi Yamamoto, Asako Mitani, Mutsumi Nishida, Takanori Teshima, Masaharu Nishimura
Respiratory investigation, 59, 1, 145, 148, 2021年01月, ［国際誌］
英語, 研究論文（学術雑誌）, Pulmonary diffusing capacity for carbon monoxide (DLCO) is a valuable pulmonary function test to evaluate the gas exchange capacity of the lungs. Generally, DLCO values are significantly lower in patients with chronic obstructive pulmonary disease (COPD), particularly in those with a predominantly emphysema phenotype. However, it is extremely rare that DLCO values cannot be obtained for reasons other than technical errors. Herein, we report two patients with COPD in whom DLCO values were undetectable without prolonging the breath-holding time for the test. We discuss possible mechanisms for these peculiar findings.

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

The Combined Usage of the Global Leadership Initiative on Malnutrition Criteria and Controlling Nutrition Status Score in Acute Care Hospitals
Asako Mitani, Takahito Iwai, Toshiaki Shichinohe, Hiroshi Takeda, Satomi Kumagai, Mutsumi Nishida, Junichi Sugita, Takanori Teshima
Annals of Nutrition and Metabolism, 77, 3, 178, 184, S. Karger AG, 2021年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, <b><i>Introduction:</i></b> The Global Leadership Initiative on Malnutrition (GLIM) lacks reliable blood tests for evaluating the nutrition status. We retrospectively compared the GLIM criteria, Controlling Nutrition Status (CONUT) score, and Subjective Global Assessment (SGA) to establish effective malnutrition screening and provide appropriate nutritional interventions according to severity. <b><i>Methods:</i></b> We classified 177 patients into 3 malnutrition categories (normal/mild, moderate, and severe) according to the GLIM criteria, CONUT score, and SGA. We investigated the malnutrition prevalence, concordance of malnutrition severity, predictability of clinical outcome, concordance by etiology, and clinical outcome by inflammation. <b><i>Results:</i></b> The highest prevalence of malnutrition was found using the GLIM criteria (87.6%). Concordance of malnutrition severity was low between the GLIM criteria and CONUT score. Concordance by etiology was low in all groups but was the highest in the “acute disease” group. The area under the curve of clinical outcome and that of the “with inflammation group” were significantly higher when using the CONUT score versus using the other tools (0.679 and 0.683, respectively). <b><i>Conclusion:</i></b> The GLIM criteria have high sensitivity, while the CONUT score can effectively predict the clinical outcome of malnutrition. Their combined use can efficiently screen for malnutrition and patient severity in acute care hospitals.

Reliability of an ultrasonographical scoring system for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation
Takahito Iwai, Mutsumi Nishida, Junichi Sugita, Yusuke Kudo, Rika Takasugi, Isao Yokota, Ryo Takagi, Hitoshi Shibuya, Shuichiro Takahashi, Takanori Teshima
Journal of Medical Ultrasonics, 48, 1, 45, 52, Springer Science and Business Media LLC, 2021年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a fatal complication after hematopoietic stem cell transplantation. We previously reported the usefulness of an ultrasonographical (US) scoring system, the Hokkaido US-based scoring system consisting of ten parameters (HokUS-10): (1) hepatomegaly in the left lobe and (2) right lobe, (3) dilatation of the main portal vein (PV), (4) hepatofugal flow in the main PV, (5) decreased velocity of the PV, (6) dilatation of the para-umbilical vein (PUV), (7) appearance of blood flow signal in the PUV, (8) gallbladder (GB) wall thickening, (9) ascites, and (10) increased resistive index of the hepatic artery, for the diagnosis of SOS/VOD. However, the reliability of this system among operators remains elusive. Therefore, we prospectively evaluated the reliability of HokUS-10. METHODS: Twenty-four healthy volunteers and 40 patients with liver dysfunction were enrolled. Inter- and intra-operator reliabilities were analyzed using three sonographers. RESULTS: The median concordance rate of HokUS-10 among three sonographers and intra-operator in 24 volunteers was 92% (95% CI: 73-98%) and 98% (95% CI: 92-100%), respectively. In all 64 cases, in terms of the reliability between two sonographers for three representative US parameters (amount of ascites, GB wall thickening, and appearance of PUV blood flow signal), the median concordance rate was more than 98% (95% CI: 86-106%). CONCLUSION: The inter- and intra-reliabilities of HokUS-10 were excellent. Thus, US might be a reliable tool for SOS/VOD diagnosis.

Older age is associated with sustained detection of SARS-CoV-2 in nasopharyngeal swab samples
Takeshi Hattori, Masaru Amishima, Daisuke Morinaga, Keisuke Kamada, Sho Nakakubo, Yu Yamashita, Yasuo Shichinohe, Shinichi Fujisawa, Mutsumi Nishida, Yasuyuki Nasuhara, Takanori Teshima, Satoshi Konno
Journal of Infection, 82, 1, 159, 198, Elsevier BV, 2021年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Low-dose anti-thymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation
Souichi Shiratori, Junichi Sugita, Shuichi Ota, Senji Kasahara, Jun Ishikawa, Takayoshi Tachibana, Yoshiki Hayashi, Goichi Yoshimoto, Tetsuya Eto, Hiromi Iwasaki, Mine Harada, Keitaro Matsuo, Takanori Teshima
Bone Marrow Transplantation, 56, 1, 129, 136, Springer Science and Business Media LLC, 2021年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Allogeneic peripheral blood stem cell transplantation (PBSCT) is associated with an increased risk of severe acute and chronic graft-versus-host disease (GVHD) compared to bone marrow transplantation. Anti-thymocyte globulin (ATG) can reduce severe acute and chronic GVHD in PBSCT; however, an optimal dose of ATG remains undefined. We conducted a multicenter phase II study to investigate safety and efficacy of low-dose ATG (a total of 2 mg/kg Thymoglobulin) in patients undergoing HLA-matched PBSCT after myeloablative conditioning. The primary endpoint was grades III-IV GVHD at 100 days. Seventy-seven patients were enrolled and 72 patients with a median age of 46.5 years were eligible for analysis. The primary endpoint, cumulative incidence of grades III-IV acute GVHD at 100 days was 1.4% (95% CI, 0.1-6.7%), which was greatly less than our pre-defined statistical threshold value (18.0%). The incidence of chronic GVHD at 1 year was also low (all-grade; 15.3%, moderate to severe; 5.6%). Non-relapse mortality, relapse, overall survival, disease-free survival, and GVHD-free, relapse-free survival at 1 year were 4.2%, 20.8%, 84.7%, 75.0%, and 69.4%, respectively. Low dose thymoglobulin is promising to reduce severe acute and chronic GVHD in HLA-matched PBSCT following myeloablative conditioning.

Pharmacokinetics of mycophenolic acid after haplo-hematopoietic stem cell transplantation in Japanese recipients
Kazuki Uchiyama, Yoshitaka Saito, Yoh Takekuma, Junichi Sugita, Takanori Teshima, Mitsuru Sugawara
Journal of Oncology Pharmacy Practice, 28, 1, 107815522098081, 107815522098081, SAGE Publications, 2020年12月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug, is used to prevent graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). Although previous studies have reported that enterohepatic circulation (EHC) of MPA, which is usually observed in MMF-treated patients, does not occur in HSCT patients, it is unclear what happens in haploidentical–HSCT (haplo-HSCT) patients, who are using post-transplant cyclophosphamide. This study was conducted to investigate MPA pharmacokinetics in haplo-HSCT patients.

Seventeen haplo-HSCT patients, who received MMF for GVHD prophylaxis, were enrolled in this study. We collected blood samples on days 14 and 28, and plasma MPA concentrations were measured by high-performance liquid chromatography; pharmacokinetic parameters such as area under the curve (AUC), mean residence time (MRT), and apparent oral clearance (CL/F) were measured with moment analysis. We also evaluated EHC as AUC_6-12h/AUC_0-12h.

There was no significant difference in MPA pharmacokinetic parameters between days 14 and 28. There was also no difference between the pharmacokinetic parameter changes and diarrhea. Additionally, varying plasma MPA concentrations suggested that MPA EHC did not occur.

In this study, we revealed the pharmacokinetics of MMF in Japanese haplo-HSCT recipients. Additionally, our study demonstrated that MPA EHC might not occur in Japanese haplo-HSCT recipients.

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

Association of Epstein–Barr virus with regression after withdrawal of immunosuppressive drugs and subsequent progression of iatrogenic immunodeficiency‐associated lymphoproliferative disorders in patients with autoimmune diseases
Katsuya Fujimoto, Kanako C. Hatanaka, Yutaka Hatanaka, Ikumi Kasahara, Satoshi Yamamoto, Takahiro Tsuji, Masanobu Nakata, Yasunari Takakuwa, Yoshihito Haseyama, Yumiko Oyamada, Masakatsu Yonezumi, Hiroaki Suzuki, Hajime Sakai, Hiroko Noguchi, Akio Mori, Hiroshi Nishihara, Takanori Teshima, Yoshihiro Matsuno
Hematological Oncology, 38, 5, 799, 807, Wiley, 2020年12月, ［査読有り］
研究論文（学術雑誌）

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

SOS/VOD評価における超音波検査スコアHokUS-3の検者再現性に関する検討　　　　　　　　　　　　　　　
岩井 孝仁, 西田 睦, 工藤 悠輔, 高杉 莉佳, 横田 勲, 高木 諒, 渋谷 斉, 高橋 秀一郎, 杉田 純一, 豊嶋 崇徳
超音波医学, 47, Suppl., S344, S344, (公社)日本超音波医学会, 2020年11月
日本語

Pembrolizumab plus lenalidomide and dexamethasone in treatment-naive multiple myeloma (KEYNOTE-185): subgroup analysis in Japanese patients
Naoki Takezako, Hiroshi Kosugi, Morio Matsumoto, Shinsuke Iida, Takayuki Ishikawa, Yukio Kondo, Kiyoshi Ando, Hirokazu Miki, Itaru Matsumura, Kazutaka Sunami, Takanori Teshima, Hiromi Iwasaki, Yasushi Onishi, Masahiro Kizaki, Koji Izutsu, Dai Maruyama, Kensei Tobinai, Razi Ghori, Mohammed Farooqui, Jason Liao, Patricia Marinello, Kenji Matsuda, Yasuhiro Koh, Takashi Shimamoto, Kenshi Suzuki
International Journal of Hematology, 112, 5, 640, 649, Springer Science and Business Media LLC, 2020年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, The global, randomized, open-label KEYNOTE-185 study closed early after an interim analysis showed an unfavorable benefit-risk profile with pembrolizumab plus lenalidomide and low-dose dexamethasone (Rd) versus Rd alone in treatment-naive, transplant-ineligible multiple myeloma. This subgroup analysis reported outcomes in the Japanese population. Patients were randomly assigned (1:1) to pembrolizumab plus Rd or Rd alone, stratified by age and International Staging System. The primary end point was progression-free survival (PFS). Fifty-two Japanese patients were randomly assigned to pembrolizumab plus Rd (n = 27) or Rd (n = 25). The median follow-up was 7.2 months (range, 0.4-13.8). The median PFS was not reached (NR); 6-month PFS was 91.2% versus 86.2% with pembrolizumab plus Rd versus Rd [hazard ratio (HR), 0.31; 95% CI, 0.06-1.63]. The median overall survival (OS) was NR; 6-month OS was 96.2% versus 95.7% with pembrolizumab plus Rd versus Rd (HR, 0.33; 95% CI, 0.03-3.72). With pembrolizumab plus Rd versus Rd, grade 3-5 adverse events occurred in 70.4% versus 69.6% of patients; serious adverse events occurred in 40.7% versus 52.5%. Although in the Japanese subgroup of KEYNOTE-185 adding pembrolizumab to Rd did not show an unfavorable risk-benefit, the analysis is limited by short follow-up and small sample size, affecting generalizability of the results.

Safety and efficacy of anti-programmed cell death-1 monoclonal antibodies before and after allogeneic hematopoietic cell transplantation for relapsed or refractory Hodgkin lymphoma: a multicenter retrospective study
Ayumu Ito, Sung-Won Kim, Ken-ichi Matsuoka, Toshiro Kawakita, Takashi Tanaka, Yoshihiro Inamoto, Tomomi Toubai, Shin-ichiro Fujiwara, Masafumi Fukaya, Tadakazu Kondo, Junichi Sugita, Miho Nara, Yuna Katsuoka, Yosuke Imai, Hideyuki Nakazawa, Ichiro Kawashima, Rika Sakai, Arata Ishii, Makoto Onizuka, Tomonari Takemura, Seitaro Terakura, Hiroatsu Iida, Mika Nakamae, Kohei Higuchi, Shinobu Tamura, Satoshi Yoshioka, Kazuto Togitani, Noriaki Kawano, Ritsuro Suzuki, Junji Suzumiya, Koji Izutsu, Takanori Teshima, Takahiro Fukuda
International Journal of Hematology, 112, 5, 674, 689, Springer Science and Business Media LLC, 2020年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, We conducted a multicenter study on anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) before/after allogeneic hematopoietic cell transplantation (allo-HCT) for Hodgkin lymphoma. Anti-PD-1 mAbs were administered to 25 patients before allo-HCT and to 20 after allo-HCT. In pre-allo-HCT setting, the median interval from the last administration to allo-HCT was 59 days. After allo-HCT, 12 patients developed non-infectious febrile syndrome requiring high-dose corticosteroid. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGvHD) were 47.1%. Eight patients who had GvHD prophylaxis with post-transplant cyclophosphamide (PTCy) had less frequent aGvHD (grade II-IV, 14.6% versus 58.8%; P = 0.086). The 1 year overall survival (OS), relapse/progression, and non-relapse mortality rates were 81.3%, 27.9%, and 8.4%. In post-allo-HCT setting, the median interval from allo-HCT to the first administration was 589 days. The overall and complete response rates were 75% and 40%. At 100 days after anti-PD-1 therapy, the cumulative incidences of grade II-IV aGvHD, moderate-to-severe chronic GvHD, and grade 3-4 immune-related toxicity were 15.0%, 30.0%, and 30.0%. While the 1 year relapse/progression rate was 47.4%, the 1 year OS probability was 89.7%. In conclusion, immune-related complications were frequent despite modifications of GvHD prophylaxis or anti-PD-1 mAb dosing. In anti-PD-1-mAb-pretreated patients, PTCy-based GvHD prophylaxis may be effective.

Reply to authors.
Isao Yokota, Kentaro Sakamaki, Peter Y Shane, Takanori Teshima
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73, 11, e3986-e3987, 2020年10月26日, ［国際誌］
英語, 研究論文（学術雑誌）

HIV薬剤耐性検査の外部精度評価での次世代シーケンサーの活用
吉田 繁, 岡田 清美, 豊嶋 崇徳, 幸村 近, 蜂谷 敦子, 松田 昌和, 齊藤 浩一, 佐藤 かおり, 藤澤 真一, 遠藤 知之, 杉浦 亙, 吉村 和久, 椎野 禎一郎, 菊地 正
臨床病理, 68, 補冊, 233, 233, (一社)日本臨床検査医学会, 2020年10月
日本語

多種動物に反応する異好抗体により複数の試薬で偽陽性を呈した1症例　　　　　　　　　　　　　　　
中野 恵一, 安田 慶子, 西田 睦, 杉田 純一, 豊嶋 崇徳
臨床化学, 49, Suppl.1, 194, 194, (一社)日本臨床化学会, 2020年10月
日本語

Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54 years old: combined results of three phase II studies
Naoyuki Uchida, Kana Matsumoto, Toru Sakura, Michihiro Hidaka, Toshihiro Miyamoto, Tetsuya Eto, Yoshinobu Maeda, Tohru Murayama, Naohito Fujishima, Goichi Yoshimoto, Kunihiko Morita, Junji Kishimoto, Takanori Teshima, Shuichi Taniguchi, Takuya Yamashita, Shin-ichiro Mori, Koichi Akashi, Mine Harada
International Journal of Hematology, 112, 4, 510, 523, Springer Science and Business Media LLC, 2020年10月, ［査読有り］
研究論文（学術雑誌）

Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy‐associated hepatitis in Japan
Takashi Kitagataya, Goki Suda, Kazunori Nagashima, Takehiko Katsurada, Koji Yamamoto, Megumi Kimura, Osamu Maehara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Yoshito Komatsu, Hiroo Hata, Satoshi Takeuchi, Takashige Abe, Jun Sakakibara‐Konishi, Takanori Teshima, Akihiro Homma, Naoya Sakamoto
Journal of Gastroenterology and Hepatology, 35, 10, 1782, 1788, Wiley, 2020年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND AND AIM: Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified. METHODS: In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data. RESULTS: Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis. CONCLUSIONS: Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.

Short-term treatment with imetelstat sensitizes hematopoietic malignant cells to a genotoxic agent via suppression of the telomerase-mediated DNA repair process
Daisuke Hidaka, Masahiro Onozawa, Naohiro Miyashita, Shota Yokoyama, Masao Nakagawa, Daigo Hashimoto, Takanori Teshima
Leukemia & Lymphoma, 61, 11, 2722, 2732, Informa UK Limited, 2020年09月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Imetelstat is a specific and competitive inhibitor of telomerase enzymatic activity. We demonstrated that imetelstat could interfere with the DNA repair process and enhance the effect of DNA damaging agents using hematological tumor cell lines. Short-term administration of imetelstat enhanced growth suppression by anticancer agents and radiation. It also upregulated γH2AX expression induced by irradiation. Immunofluorescence staining showed that both human telomerase reverse transcriptase (hTERT) and γH2AX were upregulated and co-localized in the nucleus of peripheral blood mononuclear cells after irradiation, suggesting that hTERT was involved in the DNA-DSB repair process. Imetelstat enhanced growth inhibitory effect of cytotoxic agents in short-term culture without shortening of telomeres, indicating that this effect was attributed by telomere length independent mechanism. Our results suggest that the combination of short-term treatment with imetelstat and cytotoxic agent is a promising strategy to treat a wide variety of hematopoietic malignancies.

臍帯血移植後のドナー由来細胞にモノソミー7を認めたAMLの一症例　　　　　　　　　　　　　　　
佐藤 かおり, 小栗 聡, 市川 絢子, 藤澤 真一, 西田 睦, 杉田 純一, 小野澤 真弘, 豊嶋 崇徳
日本医学検査学会抄録集, 69回, 399, 399, (一社)日本臨床衛生検査技師会, 2020年09月
日本語

Feasibility and efficacy of low‐dose pegfilgrastim for CD34 + cell mobilization in lymphoma
Hideki Goto, Daisuke Hidaka, Satoshi Yamamoto, Koji Hayasaka, Rie Michimata, Ikuko Kagawa, Kana Sunagoya, Hiroaki Iijima, Eiko Hayase, Souichi Shiratori, Kohei Okada, Junichi Sugita, Masahiro Onozawa, Daigo Hashimoto, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Chikara Shimizu, Takanori Teshima
Journal of Clinical Apheresis, 35, 5, 413, 419, Wiley, 2020年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Pegfilgrastim has equivalent efficacy to daily granulocyte colony-stimulating factor (G-CSF) in enhancing neutrophil recovery after chemotherapy, but data on its use for peripheral blood stem cell (PBSC) mobilization are limited. We evaluated the safety and efficacy of CD34+ PBSC mobilization by low-dose (3.6 mg) pegfilgrastim after chemotherapy in patients with malignant lymphoma. STUDY DESIGN AND METHODS: Twenty patients with malignant lymphoma were enrolled in this study. Cytotoxic chemotherapy was started on day 1, and 3.6 mg of pegfilgrastim was subcutaneously administered on day 7. CD34+ cells were counted in the peripheral blood daily from days 11 to 14 using a flow cytometric analysis. RESULTS: In 19 of the 20 patients (95%), the CD34+ cell counts in the peripheral blood exceeded 10 × 106/L, with a mean value of 20.3 on day 11, 38.0 on day 12, 40.3 on day 13, and 40.1 on day 14. Older age was associated with lower maximum CD34+ cell mobilization. The most frequent adverse events associated with pegfilgrastim were back pain, nausea, appetite loss, and lactate dehydrogenase elevation. CONCLUSION: Our data indicated that a single dose of 3.6 mg pegfilgrastim on day 7 after chemotherapy safely and effectively mobilized CD34+ cells.

Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma
Hideki Goto, Shinichi Makita, Koji Kato, Kota Tokushige, Taizo Fujita, Koichi Akashi, Koji Izutsu, Takanori Teshima
International Journal of Clinical Oncology, 25, 9, 1736, 1743, Springer Science and Business Media LLC, 2020年09月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）,

Tisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Here, we report the efficacy and safety of tisagenlecleucel in the Japanese subgroup.




JULIET (NCT02445248) is a single-arm, open-label, multicenter, phase 2 study involving adult patients with r/r DLBCL who either relapsed after or were ineligible for autologous stem cell transplant. Primary endpoint was best overall response rate (ORR; complete response [CR] + partial response [PR]) as judged by an independent review committee.




In Japan, of 17 patients enrolled, 9 were infused with tisagenlecleucel and completed ≥ 3 months of follow-up. Best ORR was 77.8% (7/9; 95% confidence interval, 40.0–97.2), with 5 patients (55.6%) in CR and 2 (22.2%) in PR. Cytokine release syndrome (CRS) occurred in 6 patients (66.7%), with grade 3 CRS in 2 patients (Penn grading scale). Two patients received tocilizumab. Two deaths (22.2%) occurred more than 30 days after tisagenlecleucel infusion due to disease progression, neither of which were related to tisagenlecleucel.




Tisagenlecleucel showed a high best ORR with a manageable safety profile, thus offering a new treatment option in selected Japanese patients with r/r DLBCL.

Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva
Sumio Iwasaki, Shinichi Fujisawa, Sho Nakakubo, Keisuke Kamada, Yu Yamashita, Tatsuya Fukumoto, Kaori Sato, Satoshi Oguri, Keisuke Taki, Hajime Senjo, Junichi Sugita, Kasumi Hayasaka, Satoshi Konno, Mutsumi Nishida, Takanori Teshima
Journal of Infection, 81, 2, e145, e147, Elsevier BV, 2020年08月, ［査読有り］
研究論文（学術雑誌）

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
Annie Im, Armin Rashidi, Tao Wang, Michael Hemmer, Margaret L. MacMillan, Joseph Pidala, Madan Jagasia, Steven Pavletic, Navneet S. Majhail, Daniel Weisdorf, Hisham Abdel-Azim, Vaibhav Agrawal, A. Samer Al-Homsi, Mahmoud Aljurf, Medhat Askar, Jeffery J. Auletta, Asad Bashey, Amer Beitinjaneh, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Paul Castillo, Jan Cerny, Saurabh Chhabra, Hannah Choe, Stefan Ciurea, Andrew Daly, Miguel Angel Diaz Perez, Nosha Farhadfar, Shahinaz M. Gadalla, Robert Gale, Siddhartha Ganguly, Usama Gergis, Rabi Hanna, Peiman Hematti, Roger Herzig, Gerhard C. Hildebrandt, Deepesh P. Lad, Catherine Lee, Leslie Lehmann, Lazaros Lekakis, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Pooja Khandelwal, Rodrigo Martino, Hemant S. Murthy, Taiga Nishihori, Tracey A. O'Brien, Richard F. Olsson, Sagar S. Patel, Miguel-Angel Perales, Tim Prestidge, Muna Qayed, Rizwan Romee, Hélène Schoemans, Sachiko Seo, Akshay Sharma, Melhem Solh, Roger Strair, Takanori Teshima, Alvaro Urbano-Ispizua, Marjolein Van der Poel, Ravi Vij, John L. Wagner, Basem William, Baldeep Wirk, Jean A. Yared, Steve R. Spellman, Mukta Arora, Betty K. Hamilton
Biology of Blood and Marrow Transplantation, 26, 8, 1459, 1468, Elsevier BV, 2020年08月, ［査読有り］
研究論文（学術雑誌）

Lymphocyte‐monocyte ratio (LMR) can predict bendamustine therapeutic efficacy in low‐grade B‐cell lymphoma
Joji Shimono, Koh Izumiyama, Shinichi Ito, Yutaka Tsutsmi, Takeshi Kondo, Yasutaka Kakinoki, Takanori Teshima
International Journal of Laboratory Hematology, 42, 4, 431, 438, Wiley, 2020年08月, ［査読有り］
研究論文（学術雑誌）

Create a healthy diet after transplant!
Takanori Teshima
Blood, 136, 1, 8, 9, 2020年07月02日, ［国際誌］
英語, 研究論文（学術雑誌）

Effect of graft-versus-host disease on outcomes after pediatric single cord blood transplantation
Junya Kanda, Katsutsugu Umeda, Koji Kato, Makoto Murata, Junichi Sugita, Souichi Adachi, Katsuyoshi Koh, Maiko Noguchi, Hiroaki Goto, Nao Yoshida, Maho Sato, Yuhki Koga, Tsukasa Hori, Yuko Cho, Atsushi Ogawa, Masami Inoue, Yoshiko Hashii, Yoshiko Atsuta, Takanori Teshima
Bone Marrow Transplantation, 55, 7, 1430, 1437, Springer Science and Business Media LLC, 2020年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The effect of GVHD on transplant outcomes after unrelated cord blood transplantation (UCBT) is not yet fully understood. Pediatric patients aged 0-15 years with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n = 740) were selected from the Japanese registry. Fifty percent of the patients received a UCB unit containing more than 5.0 × 107/kg total nucleated cells. The occurrence of grade III-IV acute GVHD was associated with a higher risk of non-relapse mortality (NRM, hazard ratio [HR] 4.07, P < 0.001) compared with no acute GVHD. Grade I-II acute GVHD was not associated with NRM. The occurrence of grade I-II or grade III-IV acute GVHD was not associated with a relapse risk. These findings showed that grade I-II acute GVHD carried no survival benefit and grade III-IV acute GVHD had an adverse effect (HR 1.68, P = 0.007). The occurrence of limited chronic GVHD was associated with a low risk of overall mortality (HR 0.60, P = 0.045). Severe acute GVHD should be prevented because of its association with high overall mortality and NRM in pediatric single UCBT. Mild acute GVHD provides no overall benefit. Mild chronic GVHD may be beneficial for survival.

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, eaaw0720, eaaw0720, American Association for the Advancement of Science (AAAS), 2020年07月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Graft-versus-host disease (GVHD) and infection are major obstacles to successful allogeneic hematopoietic stem cell transplantation (HSCT). Intestinal goblet cells form the mucus layers, which spatially segregate gut microbiota from host tissues. Although it is well known that goblet cell loss is one of the histologic features of GVHD, effects of their loss in pathophysiology of GVHD remain to be elucidated. In mouse models of allogeneic HSCT, goblet cells in the colon were significantly reduced, resulting in disruption of the inner mucus layer of the colon and increased bacterial translocation into colonic mucosa. Pretransplant administration of interleukin-25 (IL-25), a growth factor for goblet cells, protected goblet cells against GVHD, prevented bacterial translocation, reduced plasma concentrations of interferon-γ (IFN-γ) and IL-6, and ameliorated GVHD. The protective role of IL-25 was dependent on Lypd8, an antimicrobial molecule produced by enterocytes in the colon that suppresses motility of flagellated bacteria. In clinical colon biopsies, low numbers of goblet cells were significantly associated with severe intestinal GVHD, increased transplant-related mortality, and poor survival after HSCT. Goblet cell loss is associated with poor transplant outcome, and administration of IL-25 represents an adjunct therapeutic strategy for GVHD by protecting goblet cells.

Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification.
Tatsuya Fukumoto, Sumio Iwasaki, Shinichi Fujisawa, Kasumi Hayasaka, Kaori Sato, Satoshi Oguri, Keisuke Taki, Sho Nakakubo, Keisuke Kamada, Yu Yamashita, Satoshi Konno, Mutsumi Nishida, Junichi Sugita, Takanori Teshima
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 98, 16, 17, Elsevier BV, 2020年06月26日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for the diagnosis of coronavirus disease 2019 (COVID-19) and preventing the spread of the virus. A novel detection kit - the 2019 Novel Coronavirus Detection Kit (nCoV-DK) - halves the detection time by eliminating the steps of RNA extraction and purification. We evaluated the concordance between the nCoV-DK and direct PCR. The virus was detected in 53/71 specimens (74.6%) by direct PCR and in 55/71 specimens (77.5%) by nCoV-DK; the overall concordance rate was 94.4%: 95.2% for nasopharyngeal swab, 95.5% for saliva, and 85.7% for sputum. The nCoV-DK test effectively detects SARS-CoV-2 in all types of sample including saliva, while reducing the time required for detection, labor, and the risk of human error.

Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT
Rohtesh S. Mehta, Shernan G. Holtan, Tao Wang, Michael T. Hemmer, Stephen R. Spellman, Mukta Arora, Daniel R. Couriel, Amin M. Alousi, Joseph Pidala, Hisham Abdel-Azim, Vaibhav Agrawal, Ibrahim Ahmed, A. Samer Al-Homsi, Mahmoud Aljurf, Joseph H. Antin, Medhat Askar, Jeffery J. Auletta, Vijaya Raj Bhatt, Lynette Chee, Saurabh Chhabra, Andrew Daly, Zachariah DeFilipp, James Gajewski, Robert Peter Gale, Usama Gergis, Peiman Hematti, Gerhard C. Hildebrandt, William J. Hogan, Yoshihiro Inamoto, Rodrigo Martino, Navneet S. Majhail, David I. Marks, Taiga Nishihori, Richard F. Olsson, Attaphol Pawarode, Miguel Angel Diaz, Tim Prestidge, Hemalatha G. Rangarajan, Olle Ringden, Ayman Saad, Bipin N. Savani, Hélène Schoemans, Sachiko Seo, Kirk R. Schultz, Melhem Solh, Thomas Spitzer, Jan Storek, Takanori Teshima, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Jean-Yves Cahn, Daniel J. Weisdorf
Journal of Clinical Oncology, 38, 18, 2062, 2076, American Society of Clinical Oncology (ASCO), 2020年06月20日, ［査読有り］
研究論文（学術雑誌）, There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]–bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.

We report composite end points of graft-versus-host disease (GVHD)–free relapse-free survival (GRFS) and chronic GVHD (cGVHD)–free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant.

In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.

Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.

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

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease
Robert Zeiser, Nikolas von Bubnoff, Jason Butler, Mohamad Mohty, Dietger Niederwieser, Reuven Or, Jeff Szer, Eva M. Wagner, Tsila Zuckerman, Bruyère Mahuzier, Judith Xu, Celine Wilke, Kunal K. Gandhi, Gérard Socié
New England Journal of Medicine, 382, 19, 1800, 1810, Massachusetts Medical Society, 2020年05月07日, ［査読有り］
研究論文（学術雑誌）

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

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

Rosai-Dorfman disease: earlier spontaneous regression of skin lesions relative to nasal, pharyngeal, and bone lesions
Kazumasa Sato, Hideyuki Ujiie, Shinichi Nakazato, Mika Watanabe, Erika Watanabe, Teruki Yanagi, Yuji Nakamaru, Dai Takagi, Ryuta Arai, Tomohiro Onodera, Takeshi Kondo, Takanori Teshima, Hiroshi Shimizu
European Journal of Dermatology, 30, 2, 182, 183, John Libbey Eurotext, 2020年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

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, Springer Science and Business Media LLC, 2020年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m2 on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.

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

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

Patient-reported long-term quality of life after tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma
Richard T. Maziarz, Edmund K. Waller, Ulrich Jaeger, Isabelle Fleury, Joseph McGuirk, Harald Holte, Samantha Jaglowski, Stephen J. Schuster, Michael R. Bishop, Jason R. Westin, Stephan Mielke, Takanori Teshima, Veronika Bachanova, Stephen R. Foley, Peter Borchmann, Gilles A. Salles, Jie Zhang, Ranjan Tiwari, Lida B. Pacaud, Qiufei Ma, Constantine S. Tam
Blood Advances, 4, 4, 629, 637, American Society of Hematology, 2020年02月25日, ［査読有り］
研究論文（学術雑誌）, The JULIET phase 2 trial evaluated a single infusion of tisagenlecleucel in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The objective of the current analysis was to evaluate patient-reported health-related quality of life (HRQoL) with a median follow-up of 19.3 months among patients infused with a single dose of tisagenlecleucel. Patients enrolled were ≥18 years of age with r/r DLBCL after ≥2 lines of therapy and had either undergone a failed autologous stem cell transplant or were ineligible for the procedure. Two validated HRQoL instruments, Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and Short Form-36 (SF-36) Health Survey, were used to measure HRQoL at baseline and months 3, 6, 12, and 18. At data cutoff (21 May 2018), 115 patients had received tisagenlecleucel infusion. Among the 99 patients evaluated, overall response rate was 54%, and 40% of patients achieved complete response (CR). Initially, 108 patients completed the HRQoL assessments at baseline, including 57 patients who eventually achieved CR or partial response (PR). Further, 30 and 21 patients in clinical response who completed assessments at baseline also completed assessments at months 12 and 18, respectively. Patients who achieved CR or PR sustained HRQoL improvement in all FACT scores at all time points. SF-36 instruments showed improvement above the minimal clinically important differences on 5 of 8 subscales. Long-term follow-up in the phase 2 JULIET study demonstrated that patients with r/r DLBCL who respond to tisagenlecleucel therapy had sustained, clinically meaningful improvements in HRQoL. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

MT Seminar トロポニン測定のピットフォール
中野 恵一, 眞船 直樹, 安田 慶子, 西田 睦, 杉田 純一, 豊嶋 崇徳
Medical Technology, 48, 2, 193, 197, 医歯薬出版(株), 2020年02月
日本語

不規則抗体スクリーニング試薬0.8%セルスクリーンJ-Alba-を用い不規則抗体の早期検出が可能であった2症例
増田 裕弥, 伊藤 誠, 櫻澤 貴代, 魚住 諒, 渡邊 千秋, 西田 睦, 高橋 秀一郎, 杉田 純一, 豊嶋 崇徳
日本輸血細胞治療学会誌, 66, 1, 57, 57, (一社)日本輸血・細胞治療学会, 2020年02月
日本語

新生児におけるcisAB型の血液型検査反応性と発育に伴う抗原量の変化に関する検討
櫻澤 貴代, 高橋 秀一郎, 渡邊 千秋, 伊藤 誠, 魚住 諒, 増田 裕弥, 早坂 光司, 西田 睦, 杉田 純一, 豊嶋 崇徳
日本輸血細胞治療学会誌, 66, 1, 31, 35, (一社)日本輸血・細胞治療学会, 2020年02月, ［査読有り］
日本語

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

A Novel Strategy for SARS-CoV-2 Mass-Screening Using Quantitative Antigen Testing of Saliva
Isao Yokota, Peter Y. Shane, Kazufumi Okada, Yokota Unoki, Yichi Yang, Sumio Iwasaki, Shinichi Fujisawa, Mutsumi Nishida, Takanori Teshima
SSRN Electronic Journal, Elsevier BV, 2020年, ［査読有り］
研究論文（学術雑誌）

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

Localization of BCR-ABL to Stress Granules Contributes to Its Oncogenic Function.
Sayaka Kashiwagi, Yoichiro Fujioka, Takeshi Kondo, Aya O Satoh, Aiko Yoshida, Mari Fujioka, Hitoshi Sasajima, Maho Amano, Takanori Teshima, Yusuke Ohba
Cell structure and function, 44, 2, 195, 204, 2019年12月26日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, The oncogenic tyrosine kinase BCR-ABL activates a variety of signaling pathways and plays a causative role in the pathogenesis of chronic myelogenous leukemia (CML); however, the subcellular distribution of this chimeric protein remains controversial. Here, we report that BCR-ABL is localized to stress granules and that its granular localization contributes to BCR-ABL-dependent leukemogenesis. BCR-ABL-positive granules were not colocalized with any markers for membrane-bound organelles but were colocalized with HSP90a, a component of RNA granules. The number of such granules increased with thapsigargin treatment, confirming that the granules were stress granules. Given that treatment with the ABL kinase inhibitor imatinib and elimination of the N-terminal region of BCR-ABL abolished granule formation, kinase activity and the coiled-coil domain are required for granule formation. Whereas wild-type BCR-ABL rescued the growth defect in IL-3-depleted Ba/F3 cells, mutant BCR-ABL lacking the N-terminal region failed to do so. Moreover, forced tetramerization of the N-terminus-deleted mutant could not restore the growth defect, indicating that granule formation, but not tetramerization, through its N-terminus is critical for BCR-ABL-dependent oncogenicity. Our findings together provide new insights into the pathogenesis of CML by BCR-ABL and open a window for developing novel therapeutic strategies for this disease.Key words: BCR-ABL, subcellular localization, stress granule.

A prospective observational study of immune reconstitution following transplantation with post‐transplant reduced‐dose cyclophosphamide from HLA ‐haploidentical donors
Hirohisa Nakamae, Kazuki Fujii, Satoru Nanno, Hiroshi Okamura, Takahiko Nakane, Hideo Koh, Yasuhiro Nakashima, Mika Nakamae, Asao Hirose, Takanori Teshima, Masayuki Hino
Transplant International, 32, 12, 1322, 1332, Wiley, 2019年12月, ［査読有り］
研究論文（学術雑誌）

Carbapenem inactivation method(CIM)を応用したESBLおよびAmpCの同時検出法の開発　　　　　　　　　　　　　　　
岩崎 澄央, 福元 達也, 早坂 かすみ, 西田 睦, 杉田 純一, 豊嶋 崇徳
日本臨床微生物学会雑誌, 30, Suppl.1, 284, 284, (一社)日本臨床微生物学会, 2019年12月
日本語

Simplified Carbapenem inactivation method(sCIM)を応用したESBLおよびAmpCの同時検出法の開発　　　　　　　　　　　　　　　
福元 達也, 岩崎 澄央, 早坂 かすみ, 西田 睦, 杉田 純一, 豊嶋 崇徳
日本臨床微生物学会雑誌, 30, Suppl.1, 284, 284, (一社)日本臨床微生物学会, 2019年12月
日本語

Ibrutinib Caused Mediastinal Emphysema and Pneumothorax in the Treatment of a Patient with Mantle Cell Lymphoma
Yutaka Tsutsumi, Takahiro Sekine, Shinichi Ito, Satomi Matsuoka, Takanori Teshima
Drug Safety - Case Reports, 6, 1, 3, 3, Springer Science and Business Media LLC, 2019年12月, ［査読有り］
研究論文（学術雑誌）

Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT
Maddalena Noviello, Francesco Manfredi, Eliana Ruggiero, Tommaso Perini, Giacomo Oliveira, Filippo Cortesi, Pantaleo De Simone, Cristina Toffalori, Valentina Gambacorta, Raffaella Greco, Jacopo Peccatori, Monica Casucci, Giulia Casorati, Paolo Dellabona, Masahiro Onozawa, Takanori Teshima, Marieke Griffioen, Constantijn J. M. Halkes, J. H. F. Falkenburg, Friedrich Stölzel, Heidi Altmann, Martin Bornhäuser, Miguel Waterhouse, Robert Zeiser, Jürgen Finke, Nicoletta Cieri, Attilio Bondanza, Luca Vago, Fabio Ciceri, Chiara Bonini
Nature Communications, 10, 1, 1065, 1065, Springer Science and Business Media LLC, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The major cause of death after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for acute myeloid leukemia (AML) is disease relapse. We investigated the expression of Inhibitory Receptors (IR; PD-1/CTLA-4/TIM-3/LAG-3/2B4/KLRG1/GITR) on T cells infiltrating the bone marrow (BM) of 32 AML patients relapsing (median 251 days) or maintaining complete remission (CR; median 1 year) after HSCT. A higher proportion of early-differentiated Memory Stem (TSCM) and Central Memory BM-T cells express multiple IR in relapsing patients than in CR patients. Exhausted BM-T cells at relapse display a restricted TCR repertoire, impaired effector functions and leukemia-reactive specificities. In 57 patients, early detection of severely exhausted (PD-1+Eomes+T-bet-) BM-TSCM predicts relapse. Accordingly, leukemia-specific T cells in patients prone to relapse display exhaustion markers, absent in patients maintaining long-term CR. These results highlight a wide, though reversible, immunological dysfunction in the BM of AML patients relapsing after HSCT and suggest new therapeutic opportunities for the disease.

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

Using a machine learning algorithm to predict acute graft-versus-host disease following allogeneic transplantation.
Yasuyuki Arai, Tadakazu Kondo, Kyoko Fuse, Yasuhiko Shibasaki, Masayoshi Masuko, Junichi Sugita, Takanori Teshima, Naoyuki Uchida, Takahiro Fukuda, Kazuhiko Kakihana, Yukiyasu Ozawa, Tetsuya Eto, Masatsugu Tanaka, Kazuhiro Ikegame, Takehiko Mori, Koji Iwato, Tatsuo Ichinohe, Yoshinobu Kanda, Yoshiko Atsuta
Blood advances, 3, 22, 3626, 3634, 2019年11月26日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Acute graft-versus-host disease (aGVHD) is 1 of the critical complications that often occurs following allogeneic hematopoietic stem cell transplantation (HSCT). Thus far, various types of prediction scores have been created using statistical calculations. The primary objective of this study was to establish and validate the machine learning-dependent index for predicting aGVHD. This was a retrospective cohort study that involved analyzing databases of adult HSCT patients in Japan. The alternating decision tree (ADTree) machine learning algorithm was applied to develop models using the training cohort (70%). The ADTree algorithm was confirmed using the hazard model on data from the validation cohort (30%). Data from 26 695 HSCT patients transplanted from allogeneic donors between 1992 and 2016 were included in this study. The cumulative incidence of aGVHD was 42.8%. Of >40 variables considered, 15 were adapted into a model for aGVHD prediction. The model was tested in the validation cohort, and the incidence of aGVHD was clearly stratified according to the categorized ADTree scores; the cumulative incidence of aGVHD was 29.0% for low risk and 58.7% for high risk (hazard ratio, 2.57). Predicting scores for aGVHD also demonstrated the link between the risk of development aGVHD and overall survival after HSCT. The machine learning algorithms produced clinically reasonable and robust risk stratification scores. The relatively high reproducibility and low impacts from the interactions among the variables indicate that the ADTree algorithm, along with the other data-mining approaches, may provide tools for establishing risk score.

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, (一社)日本血液学会-東京事務局, 2019年11月
日本語

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, 2019年11月
日本語

Clinical efficacy and safety of first-line nilotinib therapy and evaluation of the clinical utility of the FRET-based drug sensitivity test.
Takeshi Kondo, Mari Fujioka, Shinichi Fujisawa, Kaori Sato, Masumi Tsuda, Takuto Miyagishima, Akio Mori, Hiroshi Iwasaki, Yasutaka Kakinoki, Satoshi Yamamoto, Yoshihito Haseyama, Seisho Ando, Motohiro Shindo, Shuichi Ota, Mitsutoshi Kurosawa, Yusuke Ohba, Takanori Teshima
International journal of hematology, 110, 4, 482, 489, 2019年10月, ［査読有り］, ［国内誌］
英語, Nilotinib is widely used for primary treatment of patients with chronic myelogenous leukemia (CML). We previously reported that use of an FRET-based drug sensitivity test at diagnosis efficiently predicts the response to treatment with imatinib or dasatinib. Here, we conducted a phase-II study to evaluate the efficacy and safety of nilotinib treatment and identify useful biomarkers, including results of the FRET-based drug sensitivity test, for predicting treatment response. Data from 42 patients were used in the analysis. Major molecular response (MMR), MR4, and MR4.5 rates at 12 months were 64.3, 42.9, and 28.6%, respectively. Grade 3/4 non-hematologic adverse events occurred in 11 patients (26.2%). The dose intensity of nilotinib (> 76.44%) and halving time (HT, < 13.312 days) were identified as significant factors for MMR at 12 months. However, when we focused on patients whose dose intensity of nilotinib was > 76.44%, the FRET-based drug sensitivity test became a predictive factor of MR4 achievement at 12 months. Our study reconfirmed the efficacy and safety of nilotinib treatment in CML patients. Moreover, our results suggest that the FRET-based drug sensitivity test is an independent predictor for achievement of MR4 in patients treated with a sufficient dose intensity of nilotinib.

北海道大学病院における血液培養陽性検体でのDISK法による薬剤中間報告の有用性　　　　　　　　　　　　　　　
福元 達也, 岩崎 澄央, 早坂 かすみ, 西田 睦, 杉田 純一, 豊嶋 崇徳
臨床病理, 67, 補冊, 144, 144, (一社)日本臨床検査医学会, 2019年10月
日本語

Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial
Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, Yimer HA, LeBlanc R, Takezako N, McCroskey RD, Lim ABM, Suzuki K, Kosugi H, Grigoriadis G, Avivi I, Facon T, Jagannath S, Lonial S, Ghori RU, Farooqui MZH, Marinello P, San-Miguel J, KEYNOTE, Investigators
Lancet Haematol, 6, 9, e448, e458, 2019年09月, ［査読有り］

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

G-bandで非典型転座様式を示しDEK-NUP214 mRNA検出が核型決定に有用であったAMLの一症例
佐藤 かおり, 小栗 聡, 市川 絢子, 藤澤 真一, 西田 睦, 高橋 秀一郎, 杉田 純一, 豊嶋 崇徳
日本染色体遺伝子検査学会雑誌, 37, 2, 48, 48, 日本染色体遺伝子検査学会, 2019年09月
日本語

脾臓への放射線照射が奏功した脾機能亢進症の1例　　　　　　　　　　　　　　　
岩崎 愛美, 安田 耕一, 遠藤 知之, 大東 寛幸, 清水 伸一, 鬼丸 力也, 豊嶋 崇徳, 白土 博樹
日本医学放射線学会秋季臨床大会抄録集, 55回, S518, S518, (公社)日本医学放射線学会, 2019年09月
日本語

Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
Ayman Saad, Lawrence Lamb, Tao Wang, Michael T. Hemmer, Stephen Spellman, Daniel Couriel, Amin Alousi, Joseph Pidala, Hisham Abdel-Azim, Vaibhav Agrawal, Mahmoud Aljurf, Amer M. Beitinjaneh, Vijaya Raj Bhatt, David Buchbinder, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Paul Castillo, Saurabh Chhabra, Miguel Angel Diaz, Shatha Farhan, Yngvar Floisand, Hadar A. Frangoul, Shahinaz M. Gadalla, James Gajewski, Robert Peter Gale, Manish Gandhi, Usama Gergis, Betty Ky Hamilton, Peiman Hematti, Gerhard C. Hildebrandt, Rammurti T. Kamble, Abraham S. Kanate, Pooja Khandelwal, Aleksandr Lazaryan, Margaret MacMillan, David I. Marks, Rodrigo Martino, Parinda A. Mehta, Taiga Nishihori, Richard F. Olsson, Sagar S. Patel, Muna Qayed, Hemalatha G. Rangarajan, Ran Reshef, Olle Ringden, Bipin N. Savani, Harry C. Schouten, Kirk R. Schultz, Sachiko Seo, Brian C. Shaffer, Melhem Solh, Takanori Teshima, Alvaro Urbano-Ispizua, Leo F. Verdonck, Ravi Vij, Edmund K. Waller, Basem William, Baldeep Wirk, Jean A. Yared, Lolie C. Yu, Mukta Arora, Shahrukh Hashmi
Biology of Blood and Marrow Transplantation, 25, 9, 1875, 1883, Elsevier BV, 2019年09月, ［査読有り］
研究論文（学術雑誌）

Resolved versus Active Chronic Graft-versus-Host Disease: Impact on Post-Transplantation Quality of Life
Saiko Kurosawa, Takuhiro Yamaguchi, Kumi Oshima, Atsumi Yanagisawa, Takahiro Fukuda, Heiwa Kanamori, Takehiko Mori, Satoshi Takahashi, Tadakazu Kondo, Akio Kohno, Koichi Miyamura, Yukari Umemoto, Takanori Teshima, Shuichi Taniguchi, Takuya Yamashita, Yoshihiro Inamoto, Yoshinobu Kanda, Shinichiro Okamoto, Yoshiko Atsuta
Biology of Blood and Marrow Transplantation, 25, 9, 1851, 1858, Elsevier BV, 2019年09月, ［査読有り］
研究論文（学術雑誌）

Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation
Betty K. Hamilton, Ying Liu, Michael T. Hemmer, Navneet Majhail, Olle Ringden, Dennis Kim, Luciano Costa, Robert Stuart, Amin Alousi, Joseph A. Pidala, Daniel R. Couriel, Mahmoud Aljurf, Joseph H. Antin, Christopher Bredeson, Jean-Yves Cahn, Mitchell Cairo, Sung Won Choi, Christopher Dandoy, Robert Peter Gale, Usama Gergis, Peiman Hematti, Yoshihiro Inamoto, Rammurti T. Kamble, Margaret MacMillan, David I. Marks, Eneida Nemecek, Taiga Nishihori, Ayman Saad, Bipin N. Savani, Jeff Schriber, Sachiko Seo, Gérard Socié, Takanori Teshima, Leo F. Verdonck, Edmund K. Waller, Mona Wirk, Stephen R. Spellman, Mukta Arora, Saurabh Chhabra
Biology of Blood and Marrow Transplantation, 25, 9, 1744, 1755, Elsevier BV, 2019年09月, ［査読有り］
研究論文（学術雑誌）

Clinical significance of end-diastolic opening of pulmonary valve in a case complicating left ventricular systolic dysfunction.
Hisao Nishino, Hiroyuki Iwano, Sanae Kaga, Mutsumi Nishida, Koji Akizawa, Takanori Teshima, Toshihisa Anzai
Journal of echocardiography, 19, 1, 53, 55, 2019年08月03日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）

IgG4による抗IgE作用の生理的意義解析 IgG4-IgE複合体がIgE測定値に与える影響　　　　　　　　　　　　　　　
中野 恵一, 眞船 直樹, 安田 慶子, 西田 睦, 杉田 純一, 豊嶋 崇徳
臨床化学, 48, Suppl.1, 282, 282, (一社)日本臨床化学会, 2019年08月
日本語

Anagrelide Modulates Proplatelet Formation Resulting in Decreased Number and Increased Size of Platelets.
Naohiro Miyashita, Masahiro Onozawa, Shota Yokoyama, Daisuke Hidaka, Koji Hayasaka, Shinji Kunishima, Takanori Teshima
HemaSphere, 3, 4, e268, 2019年08月, ［国際誌］
英語, 研究論文（学術雑誌）, We retrospectively evaluated 48 essential thrombocythemia (ET) patients who were treated in our institute (male/female, 14/34, median age, 61.5 years). In 14 patients treated with anagrelide (ANA), the degree of platelet count reduction (median, -56.6%) was strongly correlated with increase of mean platelet volume (MPV) (median, +11.7%) (R = 0.777). This correlation was not observed in ET patients treated with hydroxycarbamide alone (R = 0.245). The change in size of platelets strongly suggested that ANA affected the final process of platelet production. Thus, we hypothesized that ANA modifies the process by which platelets are released from proplatelets. To verify the association in an in vitro setting, we compared MEG-01 cells treated with PMA ± ANA. The number of platelet-like particles (PLPs) was decreased (P < 0.05) and the size of PLPs estimated by using flow cytometry was significantly increased when MEG-01 cells were treated with PMA + ANA (P < 0.05 vs PMA alone), recapitulating the clinical findings. The cytoplasmic protrusions extending from MEG-01 cells were shorter and thicker and the number of proplatelets was decreased when MEG-01 cells were treated with PMA + ANA (P < 0.01 vs PMA alone). Western blotting analysis showed that ANA treatment resulted in increased phosphorylation of MLC2 and reduced phosphorylation of focal adhesion kinase (FAK). The morphological change of proplatelets were reversed by blebbistatin, a specific inhibitor of myosin II. These findings indicated that ANA modulates the FAK-RhoA-ROCK-MLC2-myosine IIA pathway and suppresses proplatelet maturation, leading to a decrease in platelet count and increase in MPV.

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

Validation of US evaluation of ulcerative colitis activity
Satomi Omotehara, Mutsumi Nishida, Kenji Kinoshita, Reizo Onishi, Aki Onodera, Mitsuhisa Suya, Toru Hasegawa, Daiki Mitsumori, Takehiko Katsurada, Takanori Teshima
Ultrasound in Medicine & Biology, 45, 7, 1537, 1544, Elsevier BV, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, This study was aimed at validating the inter-rater grading agreement for assessing disease activity in patients with established ulcerative colitis (UC) using transabdominal ultrasonography (US) versus colonoscopy (CS). Fifty-seven patients underwent US and CS at four facilities. UC disease activity was assessed using the original US grading system and CS Matts classification. Initially, the US and CS grades were assessed at each examining facility, and still images and movie clips were re-assessed at the central facility. Grading agreement between the examining and central facilities was evaluated. Grading agreement for US and CS were 0.75 and 0.72 in all segments and 0.82 and 0.70 in the maximum grade of each patient, respectively (all p < 0.001). US grading agreement was "almost perfect" for the maximum grade and "moderate" to "substantial" for other assessments. The inter-rater US grading agreement was good and not inferior to that of CS for evaluating UC disease activity.

Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas
Keisuke Kataoka, Hiroaki Miyoshi, Seiji Sakata, Akito Dobashi, Lucile Couronné, Yasunori Kogure, Yasuharu Sato, Kenji Nishida, Yuka Gion, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Chiba, Yosaku Watatani, Nobuyuki Kakiuchi, Yusuke Shiozawa, Tetsuichi Yoshizato, Kenichi Yoshida, Hideki Makishima, Masashi Sanada, Masahiro Onozawa, Takanori Teshima, Yumiko Yoshiki, Tadao Ishida, Kenshi Suzuki, Kazuyuki Shimada, Akihiro Tomita, Motohiro Kato, Yasunori Ota, Koji Izutsu, Ayako Demachi-Okamura, Yoshiki Akatsuka, Satoru Miyano, Tadashi Yoshino, Philippe Gaulard, Olivier Hermine, Kengo Takeuchi, Koichi Ohshima, Seishi Ogawa
Leukemia, 33, 7, 1687, 1699, Springer Science and Business Media LLC, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic aberrations in 384 samples from various lymphoma subtypes using high-throughput sequencing, particularly focusing on virus-associated lymphomas. A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive lymphomas [33 (22%) of 148 cases], including extranodal NK/T-cell lymphoma (ENKTL, 23%), aggressive NK-cell leukemia (57%), systemic EBV-positive T-cell lymphoproliferative disorder (17%) as well as EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) and peripheral T-cell lymphoma-not otherwise specified (15%). Predominantly causing a truncation of the 3'-untranslated region, these alterations represented the most prevalent somatic lesions in ENKTL. By contrast, the frequency was much lower in EBV-negative lymphomas regardless of histology type [12 (5%) of 236 cases]. Besides PD-L1/PD-L2 alterations, EBV-positive DLBCL exhibited a genetic profile distinct from EBV-negative one, characterized by frequent TET2 and DNMT3A mutations and the paucity of CD79B, MYD88, CDKN2A, and FAS alterations. Our findings illustrate unique genetic features of EBV-associated lymphomas, also suggesting a potential role of detecting PD-L1/PD-L2-involving lesions for these lymphomas to be effectively targeted by immune checkpoint blockade.

新生児のcis A2B3型の判定にABO遺伝子タイピングが有用であった1例
上床 貴代, 渡邊 千秋, 伊藤 誠, 魚住 諒, 林 泰弘, 早坂 光司, 秋沢 宏次, 早瀬 英子, 豊嶋 崇徳
日本輸血細胞治療学会誌, 65, 3, 652, 652, (一社)日本輸血・細胞治療学会, 2019年06月
日本語

抗Dによる胎児・新生児溶血性疾患で胎児輸血が必要となった1症例
魚住 諒, 渡邊 千秋, 伊藤 誠, 上床 貴代, 林 泰弘, 早坂 光司, 馬詰 武, 早瀬 英子, 秋沢 宏次, 豊嶋 崇徳
日本輸血細胞治療学会誌, 65, 3, 652, 652, (一社)日本輸血・細胞治療学会, 2019年06月
日本語

新生児に対する輸血回数と曝露ドナー数の検討
林 泰弘, 渡邊 千秋, 猪股 百華, 伊藤 誠, 上床 貴代, 魚住 諒, 秋沢 宏次, 早瀬 英子, 豊嶋 崇徳
日本輸血細胞治療学会誌, 65, 3, 653, 654, (一社)日本輸血・細胞治療学会, 2019年06月
日本語

Myasthenia gravis after allogeneic bone marrow transplantation: A case report and literature review
Yutaka Tsutsumi, Takashi Kamiishi, Ryo Kikuchi, Shinichi Ito, Satomi Matsuoka, Takanori Teshima
Hematology/Oncology and Stem Cell Therapy, 12, 2, 110, 114, Elsevier BV, 2019年06月, ［査読有り］
研究論文（学術雑誌）

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia
Rohtesh S. Mehta, Shernan G. Holtan, Tao Wang, Michael T. Hemmer, Stephen R. Spellman, Mukta Arora, Daniel R. Couriel, Amin M. Alousi, Joseph Pidala, Hisham Abdel-Azim, Ibrahim Ahmed, Mahmoud Aljurf, Medhat Askar, Jeffery J. Auletta, Vijaya Bhatt, Christopher Bredeson, Saurabh Chhabra, Shahinaz Gadalla, James Gajewski, Robert Peter Gale, Usama Gergis, Peiman Hematti, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Carrie Kitko, Pooja Khandelwal, Margaret L. MacMillan, Navneet Majhail, David I. Marks, Parinda Mehta, Taiga Nishihori, Richard F. Olsson, Attaphol Pawarode, Miguel Angel Diaz, Tim Prestidge, Muna Qayed, Hemalatha Rangarajan, Olle Ringden, Ayman Saad, Bipin N. Savani, Sachiko Seo, Ami Shah, Niketa Shah, Kirk R. Schultz, Melhem Solh, Thomas Spitzer, Jeffrey Szer, Takanori Teshima, Leo F. Verdonck, Kirsten M. Williams, Baldeep Wirk, John Wagner, Jean A. Yared, Daniel J. Weisdorf
Blood Advances, 3, 9, 1441, 1449, American Society of Hematology, 2019年05月14日, ［査読有り］
研究論文（学術雑誌）,
We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy–requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen–mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P &lt; .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation–based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P &lt; .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

HIV診療がカウンセラーのチーム医療への姿勢に与える影響の解析 2015・2016年度HIV医療体制班アンケート調査から
石田 陽子, 横幕 能行, 中川 雄真, 小松 賢亮, 渡邊 愛祈, 木村 聡太, 松岡 亜由子, 豊嶋 崇徳, 小島 賢一
日本エイズ学会誌, 21, 2, 111, 117, (一社)日本エイズ学会, 2019年05月, ［査読有り］
日本語

Clinicopathological features of HCV-positive splenic diffuse large B cell lymphoma.
Joji Shimono, Hiroaki Miyoshi, Fumiko Arakawa, Kyohei Yamada, Takeshi Sugio, Kohta Miyawaki, Tetsuya Eto, Takuto Miyagishima, Koji Kato, Koji Nagafuji, Koichi Akashi, Takanori Teshima, Koichi Ohshima
Annals of hematology, 98, 5, 1197, 1207, 2019年05月, ［査読有り］, ［国際誌］
英語, The hepatitis C virus (HCV) is a single-stranded RNA virus which is thought to be involved in the onset of B cell lymphoma. HCV-positive diffuse large B cell lymphoma (DLBCL) has been reported to clinically manifest in extranodal lesions (e.g., in the liver, spleen, and stomach). Here, we investigated HCV-positive and -negative primary splenic DLBCL (p-spDLBCL) and non-primary splenic DLBCL (ordinary DLBCL). Furthermore, to examine HCV lymphomagenesis, RNA in situ hybridization (ISH), RT-PCR (reverse-transcription polymerase chain reaction), and NS3 immunostaining of HCV viral nonstructural proteins were performed. HCV-positive p-spDLBCL patients presented fewer B symptoms (asymptomatic) and better performance status, with elevated presence of splenic macronodular lesions and more germinal center B cell (GCB) sub-group cases than HCV-negative p-spDLBCL patients. However, HCV-positive ordinary DLBCL patients were found to have more non-GCB sub-group cases than HCV-negative ordinary DLBCL patients. HCV-positive DLBCL patients showed 20.6% (7/34) NS3 positivity, 16.7% (1/6) HCV-RNA in situ positivity, and 22.2% (2/9) detection of HCV-RNA in tumor tissue by RT-PCR. Splenic samples were found to have a higher frequency of HCV detection than lymph node samples, thus suggesting that HCV may be closely related to lymphomagenesis, especially in splenic lymphoma.

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, American Society of Hematology, 2019年04月09日, ［査読有り］
研究論文（学術雑誌）, Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A–coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.

A pitfall of serum troponin assay; an estrangement of cardiac troponin T and I　　　　　　　　　　　　　　　
Keiichi Nakano, Naoki Mafune, Keiko Yasuda, Koji Akizawa, Junichi Sugita, Takanori Teshima
Japanese Journal of Clinical Chemistry, 48, 2, 130, 136, Japanese Journal of Clinical Chemistry, 2019年04月01日
日本語, 研究論文（学術雑誌）

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

超音波診断をググッとあげる!こんな時どう考える? できる技師のスキルアップ術
工藤 悠輔, 西田 睦, 澁谷 斉, 豊嶋 崇徳
超音波検査技術, 44, Suppl., S105, S105, (一社)日本超音波検査学会, 2019年04月
日本語

免疫チェックポイント阻害薬関連大腸炎3例の超音波所見　　　　　　　　　　　　　　　
表原 里実, 西田 睦, 長島 一哲, 桂田 武彦, 村中 徹人, 小松 嘉人, 澁谷 斉, 秋沢 宏次, 杉田 純一, 豊嶋 崇徳
超音波医学, 46, Suppl., S650, S650, (公社)日本超音波医学会, 2019年04月
日本語

初回治療から18年後に生じた多臓器進展を伴うホジキンリンパ腫の一剖検例　　　　　　　　　　　　　　　
五味川 龍, 杉野 弘和, 白鳥 聡一, 石田 雄介, 王 磊, 畑中 佳奈子, 松野 吉宏, 豊嶋 崇徳, 田中 伸哉
日本病理学会会誌, 108, 1, 453, 453, (一社)日本病理学会, 2019年04月
日本語

Gene Polymorphism of Tacrolimus-Metabolizing Enzymes Associated With Impaired Absorption of Tacrolimus Following Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report
S. Matsuoka, Y. Tsutsumi, R. Kikuchi, S. Ito, T. Teshima
Transplantation Proceedings, 51, 3, 998, 1001, Elsevier BV, 2019年04月, ［査読有り］
研究論文（学術雑誌）

Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation
Cristina Toffalori, Laura Zito, Valentina Gambacorta, Michela Riba, Giacomo Oliveira, Gabriele Bucci, Matteo Barcella, Orietta Spinelli, Raffaella Greco, Lara Crucitti, Nicoletta Cieri, Maddalena Noviello, Francesco Manfredi, Elisa Montaldo, Renato Ostuni, Matteo M. Naldini, Bernhard Gentner, Miguel Waterhouse, Robert Zeiser, Jurgen Finke, Maher Hanoun, Dietrich W. Beelen, Ivana Gojo, Leo Luznik, Masahiro Onozawa, Takanori Teshima, Raynier Devillier, Didier Blaise, Constantijn J. M. Halkes, Marieke Griffioen, Matteo G. Carrabba, Massimo Bernardi, Jacopo Peccatori, Cristina Barlassina, Elia Stupka, Dejan Lazarevic, Giovanni Tonon, Alessandro Rambaldi, Davide Cittaro, Chiara Bonini, Katharina Fleischhauer, Fabio Ciceri, Luca Vago
Nature Medicine, 25, 4, 603, 611, Springer Science and Business Media LLC, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple costimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells. Likewise, we documented the frequent loss of surface expression of HLA-DR, -DQ and -DP on leukemia cells, due to downregulation of the HLA class II regulator CIITA. We show that loss of HLA class II expression and upregulation of inhibitory checkpoint molecules represent alternative modalities to abolish AML recognition from donor-derived T cells, and can be counteracted by interferon-γ or checkpoint blockade, respectively. Our results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies.

Quantitative detection of IKZF1 deletion by digital PCR in patients with acute lymphoblastic leukemia.
Junichi Hashiguchi, Masahiro Onozawa, Kohei Okada, Toraji Amano, Kanako C Hatanaka, Hiroshi Nishihara, Norihiro Sato, Takanori Teshima
International journal of laboratory hematology, 41, 2, e38-e40, e40, 2019年04月, ［査読有り］, ［国際誌］
英語

関節エコーで診るリウマチ性疾患の病態と治療戦略 技師による関節エコーの現状と展望　　　　　　　　　　　　　　　
西田 睦, 澁谷 斉, 豊嶋 崇徳
日本リウマチ学会総会・学術集会プログラム・抄録集, 63回, 192, 192, (一社)日本リウマチ学会, 2019年03月
日本語

Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide
Junichi Sugita, Yusuke Kagaya, Toshihiro Miyamoto, Yasuhiko Shibasaki, Koji Nagafuji, Shuichi Ota, Tatsuo Furukawa, Miho Nara, Koichi Akashi, Shuichi Taniguchi, Mine Harada, Keitaro Matsuo, Takanori Teshima
Bone Marrow Transplantation, 54, 3, 432, 441, Springer Science and Business Media LLC, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We conducted two parallel prospective, multicenter, phase II studies to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) following myeloablative conditioning (MAC, n = 50) and reduced-intensity conditioning (RIC, n = 77). Event-free survival (EFS) at 1-year as for primary endpoint was 64% and 43% in the MAC and RIC groups, respectively. Neutrophil engraftment was achieved in 98% and 94% in the MAC and RIC groups, respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 18% and 8% in the MAC group, and 14% and 5% in the RIC group, respectively. Those of all grade and moderate to severe chronic GVHD at 2-year were 36% and 20% in the MAC group, and 27% and 20% in the RIC group, respectively. Overall survival (OS), EFS, nonrelapse mortality, and relapse rate at 2-year were 68%, 54%, 10%, and 36% in the MAC group, and 44%, 35%, 20%, and 45% in the RIC group, respectively. Notably, 83% and 86% of patients who survived without relapse stopped immunosuppressant at 2-year in the MAC and RIC groups, respectively. Our results indicate that both MAC and RIC are valid options for PTCy-haploPBSCT for adults with hematological malignancies.

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

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

A role for IL-34 in osteolytic disease of multiple myeloma
Muhammad Baghdadi, Kozo Ishikawa, Sayaka Nakanishi, Tomoki Murata, Yui Umeyama, Takuto Kobayashi, Yosuke Kameda, Hiraku Endo, Haruka Wada, Bjarne Bogen, Satoshi Yamamoto, Keisuke Yamaguchi, Ikumi Kasahara, Hiroshi Iwasaki, Mutsumi Takahata, Makoto Ibata, Shuichiro Takahashi, Hideki Goto, Takanori Teshima, Ken-ichiro Seino
Blood Advances, 3, 4, 541, 551, American Society of Hematology, 2019年02月26日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Multiple myeloma (MM) is a hematological malignancy that grows in multiple sites of the axial skeleton and causes debilitating osteolytic disease. Interleukin-34 (IL-34) is a newly discovered cytokine that acts as a ligand of colony-stimulating factor-1 (CSF-1) receptor and can replace CSF-1 for osteoclast differentiation. In this study, we identify IL-34 as an osteoclastogenic cytokine that accelerates osteolytic disease in MM. IL-34 was found to be expressed in the murine MM cell line MOPC315.BM, and the expression of IL-34 was enhanced by stimulation with proinflammatory cytokines or by bone marrow (BM) stromal cells. MM-cell–derived IL-34 promoted osteoclast formation from mouse BM cells in vitro. Targeting Il34 by specific small interfering RNA impaired osteoclast formation in vitro and attenuated osteolytic disease in vivo. In BM aspirates from MM patients, the expression levels of IL-34 in CD138+ populations vary among patients from high to weak to absent. MM cell–derived IL-34 promoted osteoclast formation from human CD14+ monocytes, which was reduced by a neutralizing antibody against IL-34. Taken together, this study describes for the first time the expression of IL-34 in MM cells, indicating that it may enhance osteolysis and suggesting IL-34 as a potential therapeutic target to control pathological osteoclastogenesis in MM patients.

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

Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors.
Manabu Wakamatsu, Seitaro Terakura, Kazuteru Ohashi, Takahiro Fukuda, Yukiyasu Ozawa, Heiwa Kanamori, Masashi Sawa, Naoyuki Uchida, Shuichi Ota, Akiko Matsushita, Yoshinobu Kanda, Hirohisa Nakamae, Tatsuo Ichinohe, Koji Kato, Makoto Murata, Yoshiko Atsuta, Takanori Teshima
Blood advances, 3, 2, 105, 115, 2019年01月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; P = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; P = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; P =03) with CB, whereas it improved GRFS (HR, 0.515; P < .01) and decreased grades II to IV aGVHD (HR, 0.576; P < .01), extensive cGVHD (HR, 0.460; P = .02), and NRM (HR, 0.545; P = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Stephen J. Schuster, Michael R. Bishop, Constantine S. Tam, Edmund K. Waller, Peter Borchmann, Joseph P. McGuirk, Ulrich Jäger, Samantha Jaglowski, Charalambos Andreadis, Jason R. Westin, Isabelle Fleury, Veronika Bachanova, S. Ronan Foley, P. Joy Ho, Stephan Mielke, John M. Magenau, Harald Holte, Serafino Pantano, Lida B. Pacaud, Rakesh Awasthi, Jufen Chu, Özlem Anak, Gilles Salles, Richard T. Maziarz
New England Journal of Medicine, 380, 1, 45, 56, Massachusetts Medical Society, 2019年01月03日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. METHODS: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. RESULTS: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found. CONCLUSIONS: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel. (Funded by Novartis; JULIET ClinicalTrials.gov number, NCT02445248 .).

Phase I study of ibrutinib in Japanese patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma.
Hirohiko Shibayama, Takanori Teshima, Ilseung Choi, Kiyohiko Hatake, Naohiro Sekiguchi, Nozomi Yoshinari
Journal of clinical and experimental hematopathology : JCEH, 59, 4, 179, 186, 2019年, ［国内誌］
英語, 研究論文（学術雑誌）, This phase I study evaluated the safety and efficacy of single-agent ibrutinib in Japanese patients with treatment-naïve chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (aged 20-69 years and ineligible for chemotherapy using fludarabine or cyclophosphamide, or aged ≥70 years). Eight patients received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was safety; secondary endpoints included the overall response rate (ORR). At the time of final analysis (August 22, 2018), eight patients (all with CLL; median age, 68.5 years) had received ibrutinib for a median of 32.2 months (range, 10.4-35.9); all patients had discontinued study treatment, with 50.0% of patients switching to marketing-approved ibrutinib as subsequent anticancer therapy. All patients had ≥1 adverse event (AE); the most common AEs included a decreased platelet count, upper respiratory tract infection, increased lymphocyte count, diarrhea, nasopharyngitis, peripheral edema and rash. Four patients (50.0%) had a total of eight grade ≥3 AEs, most commonly lung infection and decreased neutrophil count. Eight serious AEs were reported in four patients (50.0%); these included a case of muscle hemorrhage (grade 3), decreased neutrophil count (grade 4) that led to dose reduction and one case of fatal cardiac arrest. The ORR was 87.5% (7/8 patients [exact 95% confidence interval 47.3-99.7]). One patient had a complete response, six had a partial response and one had a partial response with lymphocytosis. Ibrutinib had an acceptable safety profile and high ORR in Japanese patients with treatment-naïve CLL.

Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation
Saurabh Chhabra, Ying Liu, Michael T. Hemmer, Luciano Costa, Joseph A. Pidala, Daniel R. Couriel, Amin M. Alousi, Navneet S. Majhail, Robert K. Stuart, Dennis Kim, Olle Ringden, Alvaro Urbano-Ispizua, Ayman Saad, Bipin N. Savani, Brenda Cooper, David I. Marks, Gerard Socie, Harry C. Schouten, Helene Schoemans, Hisham Abdel-Azim, Jean Yared, Jean-Yves Cahn, John Wagner, Joseph H. Antin, Leo F. Verdonck, Leslie Lehmann, Mahmoud D. Aljurf, Margaret L. MacMillan, Mark R. Litzow, Melhem M. Solh, Muna Qayed, Peiman Hematti, Rammurti T. Kamble, Ravi Vij, Robert J. Hayashi, Robert P. Gale, Rodrigo Martino, Sachiko Seo, Shahrukh K. Hashmi, Taiga Nishihori, Takanori Teshima, Usama Gergis, Yoshihiro Inamoto, Stephen R. Spellman, Mukta Arora, Betty K. Hamilton
Biology of Blood and Marrow Transplantation, 25, 1, 73, 85, Elsevier BV, 2019年01月, ［査読有り］
研究論文（学術雑誌）

Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia.
Motohiro Kato, Mio Kurata, Junya Kanda, Koji Kato, Daisuke Tomizawa, Kazuko Kudo, Nao Yoshida, Kenichiro Watanabe, Hiroyuki Shimada, Jiro Inagaki, Katsuyoshi Koh, Hiroaki Goto, Keisuke Kato, Yuko Cho, Yuki Yuza, Atsushi Ogawa, Keiko Okada, Masami Inoue, Yoshiko Hashii, Takanori Teshima, Makoto Murata, Yoshiko Atsuta
Bone marrow transplantation, 54, 1, 68, 75, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage.

サイトカインリッチな成牛多血小板血漿由来血清「NeoSERA」を用いた高品質羊膜MSCの製剤化と急性GVHD・クローン病向け医師主導治験
山原 研一, 浜田 彰子, 黒田 将子, 岡田 昌也, 吉原 哲, 大西 俊介, 相馬 俊裕, 豊嶋 崇徳, 小川 啓恭, 藤盛 好裕
日本内分泌学会雑誌, 94, 4, 1573, 1573, (一社)日本内分泌学会, 2018年12月
日本語

Human Herpes Virus-6-Associated Encephalitis/Myelitis Mimicking Calcineurin Inhibitor-Induced Pain Syndrome in Allogeneic Stem Cell Transplantation Recipients
Goichi Yoshimoto, Yasuo Mori, Koji Kato, Takahiro Shima, Kohta Miyawaki, Yoshikane Kikushige, Kenjiro Kamezaki, Akihiko Numata, Takahiro Maeda, Katsuto Takenaka, Hiromi Iwasaki, Takanori Teshima, Koichi Akashi, Toshihiro Miyamoto
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 24, 12, 2540, 2548, 2018年12月, ［査読有り］
英語, 研究論文（学術雑誌）

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, Springer Science and Business Media LLC, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The R-Spondin (R-Spo) family regulates WNT signaling and stimulates the proliferation and differentiation of intestinal stem cells (ISCs). R-Spo plays a critical role in maintaining intestinal homeostasis, but endogenous producers of R-Spo in the intestine remain to be investigated. We found that R-Spo3 was the major R-Spo family member produced in the intestine and it was predominantly produced by CD45-CD90+CD31+ lymphatic endothelial cells (LECs) in the lamina propria of the intestinal mucosa. Transcriptome analysis demonstrated that LECs highly expressed R-Spo receptor, Lgr5, suggesting an autocrine stimulatory loop in LECs. LECs were significantly reduced in number, and their R-Spo3 production was impaired in intestinal graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. The impaired production of R-Spo3 in the intestine may be a novel mechanism of delayed tissue repair and defective mucosal defense in intestinal GVHD. We demonstrate a novel role of intestinal LECs in producing R-Spondin3 to maintain intestinal homeostasis.

未来の造血幹細胞移植
豊嶋 崇徳
日本輸血細胞治療学会誌, 64, 6, 675, 680, 2018年12月, ［査読有り］

Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia: A Hokkaido Leukemia Net Study
Daisuke Hidaka, Masahiro Onozawa, Junichi Hashiguchi, Naohiro Miyashita, Kohei Kasahara, Shinichi Fujisawa, Eiko Hayase, Kohei Okada, Souichi Shiratori, Hideki Goto, Junichi Sugita, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Tomoyuki Endo, Satoshi Yamamoto, Yutaka Tsutsumi, Yoshihito Haseyama, Takahiro Nagashima, Akio Mori, Shuichi Ota, Hajime Sakai, Toshimichi Ishihara, Kiyotoshi Imai, Takuto Miyagishima, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Hajime Kobayashi, Hiroshi Iwasaki, Chikara Shimizu, Takeshi Kondo, Takanori Teshima
Clinical Lymphoma Myeloma and Leukemia, 18, 11, e469, e479, Elsevier BV, 2018年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The prognostic effect of Wilms tumor 1 (WT1) expression at the diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of the present study was to determine the correlations of WT1 expression at the diagnosis of AML with established prognostic alterations. PATIENTS AND METHODS: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, single nucleotide polymorphism (SNP) in the WT1 gene (rs16754), and Fms-like tyrosine kinase receptor-3 internal tandem duplication (FLT3-ITD) mutation were analyzed for all patients. The nucleophosmin 1 (NPM1) mutation and CCAAT/enhancer-binding protein-α (CEBPA) double mutation were analyzed for cytogenetically normal (CN)-AML. The KIT mutation was analyzed for core-binding factor AML. RESULTS: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly greater than that in AML with t(8;21). In cases with CN-AML, FLT3-ITD and NPM1 mutations both correlated with greater expression of WT1, and the CEBPA double mutation was related to lower WT1 expression. The existence of both FLT3-ITD and NPM1 mutations showed synergistically greater expression of WT1 in CN-AML. SNP in the WT1 gene (rs16754) was significantly associated with lower expression of WT1. The WT1 levels were not prognostic factors in the total cohort or any cytogenetic group or stratified by SNP status. CONCLUSION: Because WT1 expression has correlated with known prognostic factors, the prognostic effect of WT1 levels could be misunderstood depending on the distribution of the collaborative mutations in each cohort. We have concluded that the prognostic significance of WT1 at the diagnosis of AML is weak compared with the other established prognostic factors.

Synchronous case of follicular lymphoma and Langerhans cell sarcoma in the same lymph node
Joji Shimono, Hiroaki Miyoshi, Fumiko Arakawa, Hideyuki Abe, Takuto Miyagishima, Jun Akiba, Takanori Teshima, Koichi Ohshima
Pathology International, 68, 11, 614, 617, Wiley, 2018年11月, ［査読有り］
研究論文（学術雑誌）

Analysis of GNA13 Protein in Follicular Lymphoma and its Association With Poor Prognosis.
Joji Shimono, Hiroaki Miyoshi, Noriaki Yoshida, Takeharu Kato, Kensaku Sato, Takeshi Sugio, Kohta Miyawaki, Daisuke Kurita, Yuya Sasaki, Keisuke Kawamoto, Yoshitaka Imaizumi, Koji Kato, Koji Nagafuji, Koichi Akashi, Masao Seto, Takanori Teshima, Koichi Ohshima
The American journal of surgical pathology, 42, 11, 1466, 1471, 2018年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, GNA13 is a G protein involved in modulating tumor proliferative capacity, infiltration, metastasis, and migration. Genomic alteration of GNA13 was frequently observed in follicular lymphoma (FL). In this study, we examined 167 cases of FL by immunostaining of GNA13 using tissue microarray to evaluate the clinical significance. There were 26 GNA13-positive cases (15.6%) and 141 GNA13-negative cases (84.4%). GNA13-positive cases had a higher incidence of early progression of disease for which disease progression was recognized within 2 years compared with GNA13-negative cases (P=0.03). There were no significant differences in other clinicopathologic factors including histological grade, BCL2-IGH translocation, immunohistochemical phenotype, and Follicular Lymphoma International Prognostic Index. In addition, overall survival and progression-free survival were poorer in GNA13-positive cases than in GNA13-negative cases (P=0.009 and 0.005, respectively). In multivariate analysis, GNA13 positivity was found to be a poor prognostic factor for overall survival and progression-free survival. Thus, GNA13 protein expression was an independent prognostic factor and may affect disease progression in FL.

HIV薬剤耐性検査の標準化に向けた取り組みの評価
吉田 繁, 蜂谷 敦子, 松田 昌和, 齊藤 浩一, 岡田 清美, 椎野 禎一郎, 加藤 真吾, 佐藤 かおり, 藤澤 真一, 豊嶋 崇徳, 杉浦 亙, 吉村 和久, 菊地 正
日本染色体遺伝子検査学会雑誌, 36, 2, 57, 57, 日本染色体遺伝子検査学会, 2018年10月
日本語

Hematogones Predict Better Outcome in Allogeneic Hematopoietic Stem Cell Transplantation Irrespective of Graft Sources
Takashi Ishio, Junichi Sugita, Takahiro Tateno, Daisuke Hidaka, Eiko Hayase, Souichi Shiratori, Kohei Okada, Hideki Goto, Masahiro Onozawa, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Takanori Teshima
Biology of Blood and Marrow Transplantation, 24, 10, 1990, 1996, Elsevier BV, 2018年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Benign precursors of B lymphocytes, termed hematogones, are observed in the regenerative state of hematopoiesis following chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated that expansion of hematogones correlates with better clinical outcomes after allo-HSCT. We retrospectively analyzed the association between hematogones and clinical outcomes in 309 consecutive patients who underwent allo-HSCT, which is the largest population-based cohort reported so far. The incidence of hematogones was significantly higher in complete remission (CR) patients at the time of transplantation than in non-CR patients, after myeloablative conditioning than after reduced-intensity conditioning, with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis than with cyclosporine-based prophylaxis, and with disease other than malignant lymphoma (all P < .05). Patients with hematogones developed less acute GVHD and infections than did those without them (P < .05). Emergence of hematogones was associated with superior GVHD-free relapse-free survival and lower nonrelapse mortality, and was an independent prognostic factor for overall survival, irrespective of donor sources.

Essential role of IFN-γ in T cell–associated intestinal inflammation
Yoshihiro Eriguchi, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuichiro Takahashi, Daigo Hashimoto, Takanori Teshima, Tokiyoshi Ayabe, Michael E. Selsted, André J. Ouellette
JCI Insight, 3, 18, e121886, e121886, American Society for Clinical Investigation, 2018年09月20日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Paneth cells contribute to small intestinal homeostasis by secreting antimicrobial peptides and constituting the intestinal stem cell (ISC) niche. Certain T cell-mediated enteropathies are characterized by extensive Paneth cell depletion coincident with mucosal destruction and dysbiosis. In this study, mechanisms of intestinal crypt injury have been investigated by characterizing responses of mouse intestinal organoids (enteroids) in coculture with mouse T lymphocytes. Activated T cells induced enteroid damage, reduced Paneth cell and Lgr5+ ISC mRNA levels, and induced Paneth cell death through a caspase-3/7-dependent mechanism. IFN-γ mediated these effects, because IFN-γ receptor-null enteroids were unaffected by activated T cells. In mice, administration of IFN-γ induced enteropathy with crypt hyperplasia, villus shortening, Paneth cell depletion, and modified ISC marker expression. IFN-γ exacerbated radiation enteritis, which was ameliorated by treatment with a selective JAK1/2 inhibitor. Thus, IFN-γ induced Paneth cell death and impaired regeneration of small intestinal epithelium in vivo, suggesting that IFN-γ may be a useful target for treating defective mucosal regeneration in enteric inflammation.

Autologous haematopoietic stem cell transplantation for Japanese patients with systemic sclerosis: Long-term follow-up on a phase II trial and treatment-related fatal cardiomyopathy
Hiroyuki Nakamura, Toshio Odani, Shinsuke Yasuda, Atsushi Noguchi, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Junichi Sugita, Tomoyuki Endo, Takanori Teshima, Tatsuya Atsumi
Modern Rheumatology, 28, 5, 879, 884, Oxford University Press (OUP), 2018年09月03日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The objective of this study is to elucidate the efficacy and safety of autologous haematopoietic stem cell transplantation (HSCT) for Japanese patients with systemic sclerosis (SSc). METHODS: A phase II clinical trial included SSc patients diagnosed within the last three years having at least one of the following clinical features: diffuse skin sclerosis with modified Rodman total thickness skin score (mRSS) ≥ 15, refractory digital ulcer or interstitial lung disease (ILD). HSCT were performed after conditioning using cyclophosphamide. RESULTS: Fourteen patients were enrolled and underwent HSCT. Median follow-up period was 137 months. Overall survival or event-free survival rate was 93% or 40% at 10 years, respectively. Eight patients (57%) achieved more than a 50% decrease in mRSS from baseline within six months after HSCT. Six patients (43%) required additional immunosuppressive treatments due to progression of diffuse skin sclerosis and/or ILD during follow-up period. Adverse events related to HSCT occurred in six patients (43%). Severe cardiomyopathy occurred in two patients, and one of them had a fatal course. CONCLUSION: HSCT is a feasible treatment bringing favourable results to more than half of our patients with SSc. Careful selection of the patients is essential for whom benefited from HSCT, considering the risk-benefit balance of the treatment.

骨髄バンクを介したコーディネート期間短縮に向けた開始ドナー人数増加(5人→10人)トライアル(Trial to increase the initial numbers of donor candidates for the donor coordination of JMDP)　　　　　　　　　　　　　　　
平川 経晃, 田島 絹子, 大橋 一輝, 豊嶋 崇徳, 大西 康, 小澤 幸泰, 加藤 剛二, 日野 雅之, 前田 嘉信, 嶋田 明, 宮本 敏浩, 白土 基明, 山口 公平, 福田 隆浩
臨床血液, 59, 9, 1630, 1630, (一社)日本血液学会-東京事務局, 2018年09月
日本語

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

日本人未治療CLL/SLL患者を対象としたIbrutinibの第I相試験(Phase 1 study of ibrutinib in Japanese patients with treatment-naive CLL/SLL)　　　　　　　　　　　　　　　
豊嶋 崇徳, 柴山 浩彦, 崔 日承, 畠 清彦, 関口 直宏, 吉成 望
臨床血液, 59, 9, 1526, 1526, (一社)日本血液学会-東京事務局, 2018年09月
英語

KEYNOTE185 未治療多発性骨髄腫を対象としたLen/dex±pembrolizumab第3相試験(日本人解析含む)(KEYNOTE185: Randomized phase 3 study of Len/dex±pembrolizumab in untreated MM: including JPN subset)　　　　　　　　　　　　　　　
小杉 浩史, 竹迫 直樹, 松本 守生, 飯田 真介, 石川 隆之, 近藤 恭夫, 安藤 潔, 張 高明, 三木 浩和, 松村 到, 角南 一貴, 豊嶋 崇徳, 岩崎 浩己, 大西 康, 木崎 昌弘, 伊豆津 宏二, 丸山 大, 飛内 賢正, 鈴木 憲史
臨床血液, 59, 9, 1610, 1610, (一社)日本血液学会-東京事務局, 2018年09月
英語

The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation
Daisuke Hidaka, Eiko Hayase, Souichi Shiratori, Yuta Hasegawa, Takashi Ishio, Takahiro Tateno, Kohei Okada, Hideki Goto, Junichi Sugita, Masahiro Onozawa, Masao Nakagawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
Clinical Transplantation, 32, 9, e13361, e13361, Wiley, 2018年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-vs-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo-SCT. Among 213 patients who underwent allo-SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.

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, 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, 20, 3, 199, 205, (一社)日本エイズ学会, 2018年08月, ［査読有り］
日本語

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

Safety, tolerability and pharmacokinetics of shorter duration of infusion of obinutuzumab in Japanese patients with B-cell non-Hodgkin lymphoma: final results of the phase II GATS study
Ken Ohmachi, Kiyoshi Ando, Tomohiro Kinoshita, Kyoya Kumagai, Kiyohiko Hatake, Takayuki Ishikawa, Takanori Teshima, Koji Kato, Koji Izutsu, Eisuke Ueda, Kiyohiko Nakai, Hiroshi Kuriki, Kensei Tobinai
Japanese Journal of Clinical Oncology, 48, 8, 736, 742, Oxford University Press (OUP), 2018年08月01日, ［査読有り］
研究論文（学術雑誌）

AMLにおけるWT1発現量と染色体・遺伝子異常の関連　　　　　　　　　　　　　　　
日高 大輔, 小野澤 真弘, 橋口 淳一, 宮下 直洋, 笠原 耕平, 藤澤 真一, 早瀬 英子, 岡田 耕平, 白鳥 聡一, 後藤 秀樹, 杉田 純一, 中川 雅夫, 加畑 馨, 橋本 大吾, 遠藤 知之, 山本 聡, 堤 豊, 長谷山 美仁, 永嶋 貴博, 盛 暁生, 太田 秀一, 酒井 基, 石原 敏道, 今井 陽俊, 宮城島 拓人, 柿木 康孝, 黒澤 光俊, 小林 一, 岩崎 博, 清水 力, 近藤 健, 豊嶋 崇徳
臨床血液, 59, 7, 964, 964, (一社)日本血液学会-東京事務局, 2018年07月
日本語

Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia
Junichi Hashiguchi, Masahiro Onozawa, Satoshi Oguri, Shinichi Fujisawa, Masahisa Tsuji, Kohei Okada, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Takeshi Kondo, Chikara Shimizu, Takanori Teshima
Journal of Molecular Diagnostics, 20, 4, 446, 454, Elsevier B.V., 2018年07月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Pretreatment evaluation of fluorescence resonance energy transfer-based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib.
Takeshi Kondo, Mari Fujioka, Masumi Tsuda, Kazunori Murai, Kohei Yamaguchi, Takuto Miyagishima, Motohiro Shindo, Takahiro Nagashima, Kentaro Wakasa, Nozomu Fujimoto, Satoshi Yamamoto, Masakatsu Yonezumi, Souichi Saito, Shinji Sato, Kazuei Ogawa, Takaaki Chou, Reiko Watanabe, Yuichi Kato, Shuichiro Takahashi, Yoshiaki Okano, Joji Yamamoto, Masatsugu Ohta, Hiroaki Iijima, Koji Oba, Satoshi Kishino, Junichi Sakamoto, Yoji Ishida, Yusuke Ohba, Takanori Teshima
Cancer science, 109, 7, 2256, 2265, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Tyrosine kinase inhibitors (TKI) are used for primary therapy in patients with newly diagnosed CML. However, a reliable method for optimal selection of a TKI from the viewpoint of drug sensitivity of CML cells has not been established. We have developed a FRET-based drug sensitivity test in which a CrkL-derived fluorescent biosensor efficiently quantifies the kinase activity of BCR-ABL of living cells and sensitively evaluates the inhibitory activity of a TKI against BCR-ABL. Here, we validated the utility of the FRET-based drug sensitivity test carried out at diagnosis for predicting the molecular efficacy. Sixty-two patients with newly diagnosed chronic phase CML were enrolled in this study and treated with dasatinib. Bone marrow cells at diagnosis were subjected to FRET analysis. The ΔFRET value was calculated by subtraction of FRET efficiency in the presence of dasatinib from that in the absence of dasatinib. Treatment response was evaluated every 3 months by the BCR-ABL1 International Scale. Based on the ΔFRET value and molecular response, a threshold of the ΔFRET value in the top 10% of FRET efficiency was set to 0.31. Patients with ΔFRET value ≥0.31 had significantly superior molecular responses (MMR at 6 and 9 months and both MR4 and MR4.5 at 6, 9, and 12 months) compared with the responses in patients with ΔFRET value <0.31. These results suggest that the FRET-based drug sensitivity test at diagnosis can predict early and deep molecular responses. This study is registered with UMIN Clinical Trials Registry (UMIN000006358).

The Microbiome and Hematopoietic Cell Transplantation: Past, Present, and Future
Tessa M. Andermann, Jonathan U. Peled, Christine Ho, Pavan Reddy, Marcie Riches, Rainer Storb, Takanori Teshima, Marcel R.M. van den Brink, Amin Alousi, Sophia Balderman, Patrizia Chiusolo, William B. Clark, Ernst Holler, Alan Howard, Leslie S. Kean, Andrew Y. Koh, Philip L. McCarthy, John M. McCarty, Mohamad Mohty, Ryotaro Nakamura, Katy Rezvani, Brahm H. Segal, Bronwen E. Shaw, Elizabeth J. Shpall, Anthony D. Sung, Daniela Weber, Jennifer Whangbo, John R. Wingard, William A. Wood, Miguel-Angel Perales, Robert R. Jenq, Ami S. Bhatt
Biology of Blood and Marrow Transplantation, 24, 7, 1322, 1340, Elsevier BV, 2018年07月, ［査読有り］
研究論文（学術雑誌）

Extracorporeal photopheresis with TC-V in Japanese patients with steroid-resistant chronic graft-versus-host disease
Shinichiro Okamoto, Takanori Teshima, Mizuha Kosugi-Kanaya, Kaoru Kahata, Naomi Kawashima, Jun Kato, Takehiko Mori, Yukiyasu Ozawa, Koichi Miyamura
International Journal of Hematology, 108, 3, 1, 8, Springer Tokyo, 2018年06月29日, ［査読有り］
英語, 研究論文（学術雑誌）

体外診断薬開発のための慢性骨髄性白血病におけるBCR-ABL活性測定用改良型FRETバイオセンサー　　　　　　　　　　　　　　　
大場 雄介, 近藤 健, 豊嶋 崇徳
臨床薬理の進歩, 39, 18, 26, (公財)臨床薬理研究振興財団, 2018年06月, ［査読有り］
日本語

Re-infection of Toxoplasma gondii after HSCT presenting lymphadenopathy resembling recurrence of lymphoma
Junichi Hashiguchi, Masahiro Onozawa, Tomoaki Naka, Kanako C. Hatanaka, Souichi Shiratori, Junichi Sugita, Katsuya Fujimoto, Yoshihiro Matsuno, Takanori Teshima
Transplant Infectious Disease, 20, 3, e12892, Blackwell Publishing Inc., 2018年06月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Graft-versus-host disease in recipients of male unrelated donor compared with parous female sibling donor transplants
Anita J. Kumar, Soyoung Kim, Michael T. Hemmer, Mukta Arora, Stephen R. Spellman, Joseph A. Pidala, Daniel R. Couriel, Amin M. Alousi, Mahmoud D. Aljurf, Jean-Yves Cahn, Mitchell S. Cairo, Corey S. Cutler, Shatha Farhan, Usama Gergis, Gregory A. Hale, Shahrukh K. Hashmi, Yoshihiro Inamoto, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Margaret L. MacMillan, David I. Marks, Hideki Nakasone, Maxim Norkin, Muna Qayed, Olle Ringden, Harry C. Schouten, Kirk R. Schultz, Melhem M. Solh, Takanori Teshima, Alvaro Urbano-Ispizua, Leo F. Verdonck, Robert Peter Gale, Betty K. Hamilton, Navneet S. Majhail, Alison W. Loren
Blood Advances, 2, 9, 1022, 1031, American Society of Hematology, 2018年05月08日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）,
Compared with parous female sibling donors, male URDs confer more aGVHD in all patients and more cGVHD in females. There was no difference in survival, relapse, or transplant mortality between recipients of parous female sibling or male URD grafts.

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

担癌患者の精査加療中、偶発的に病理組織診断された慢性リンパ性白血病/リンパ球性リンパ腫の3例
岡田 宏美, 清水 亜衣, 桑原 健, 大塚 拓也, 高桑 恵美, 岡田 耕平, 白鳥 聡一, 遠藤 知之, 豊嶋 崇徳, 三橋 智子, 松野 吉宏
日本リンパ網内系学会会誌, 58, 111, 111, (一社)日本リンパ網内系学会, 2018年05月
日本語

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

Clinicopathological analysis of polyploid diffuse large B-cell lymphoma
Joji Shimono, Hiroaki Miyoshi, Junichi Kiyasu, Tomohiko Kamimura, Tetsuya Eto, Takuto Miyagishima, Koji Nagafuji, Masao Seto, Takanori Teshima, Koichi Ohshima
PLOS ONE, 13, 4, e0194525, e0194525, Public Library of Science (PLoS), 2018年04月11日, ［査読有り］
研究論文（学術雑誌）

A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction
Naohiro Miyashita, Masahiro Onozawa, Koji Hayasaka, Takahiro Yamada, Ohsuke Migita, Kenichiro Hata, Kohei Okada, Hideki Goto, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Takeshi Kondo, Shinji Kunishima, Takanori Teshima
Annals of Hematology, 97, 4, 629, 640, Springer Science and Business Media LLC, 2018年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission
Toshihiro Miyamoto, Koji Nagafuji, Tomoaki Fujisaki, Naoyuki Uchida, Kosei Matsue, Hideho Henzan, Ryosuke Ogawa, Ken Takase, Takatoshi Aoki, Michihiro Hidaka, Takanori Teshima, Shuichi Taniguchi, Koichi Akashi, Mine Harada, For the Japan Study Group for Cell Therapy and Transplantation (JSCT)
International Journal of Hematology, 107, 4, 468, 477, Springer Tokyo, 2018年04月01日, ［査読有り］
英語, 研究論文（学術雑誌）

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

Overcoming HLA Barrier in Hematopoietic Stem Cell Transplantation
Takanori Teshima
Nihon Naika Gakkai Zasshi, 107, 3, 579, 585, Japanese Society of Internal Medicine, 2018年03月10日, ［査読有り］
日本語, 研究論文（学術雑誌）

Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells
Nimitha R. Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A. Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L. Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K. Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P. Müller, Flore Sicre-De-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E. Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M. Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis H. Kim, Daniel Weisdorf, Walter Van Der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H. Antin, Andrea S. Henden, Geoffrey R. Hill, Glen A. Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Shah, Robert S. Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas Von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A. Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R. Blazar, Robert Zeiser
Nature Medicine, 24, 3, 282, 291, Nature Publishing Group, 2018年03月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma
M. Fujisawa, M. Sakata-Yanagimoto, S. Nishizawa, D. Komori, P. Gershon, M. Kiryu, S. Tanzima, K. Fukumoto, T. Enami, M. Muratani, K. Yoshida, S. Ogawa, K. Matsue, N. Nakamura, K. Takeuchi, K. Izutsu, K. Fujimoto, T. Teshima, H. Miyoshi, P. Gaulard, K. Ohshima, S. Chiba
Leukemia, 32, 3, 694, 702, Nature Publishing Group, 2018年03月01日, ［査読有り］
英語, 研究論文（学術雑誌）

T-cell depletion effects of low-dose antithymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation
Souichi Shiratori, Mizuha Kosugi-Kanaya, Eiko Hayase, Kohei Okada, Hideki Goto, Junichi Sugita, Masahiro Onozawa, Masao Nakagawa, Kaoru Kahata, Daigo Hashimoto, Tomoyuki Endo, Takeshi Kondo, Takanori Teshima
Transplant Immunology, 46, 21, 22, Elsevier BV, 2018年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

潜伏感染III型のEBウイルスが発症に寄与したと思われる膿胸関連リンパ腫の1例
千丈 創, 盛 暁生, 金谷 穣, 泉山 康, 岡田 耕平, 竹薮 公洋, 飛岡 弘敏, 斉藤 誠, 田中 雅則, 豊嶋 崇徳, 森岡 正信
日本老年医学会雑誌, 55, 1, 143, 147, (一社)日本老年医学会, 2018年01月, ［査読有り］
日本語

Pyothorax-associated lymphoma with the expression of epstein-barr virus latent genes
Hajime Senjo, Akio Mori, Minoru Kanaya, Koh Izumiyama, Kohei Okada, Kimihiro Takeyabu, Hirotoshi Tobioka, Makoto Saito, Masanori Tanaka, Takanori Teshima, Masanobu Morioka
Japanese Journal of Geriatrics, 55, 1, 143, 147, Japan Geriatrics Society, 2018年, ［査読有り］
日本語, 研究論文（学術雑誌）

Novel Ultrasonographic Scoring System of Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation
Mutsumi Nishida, Kaoru Kahata, Eiko Hayase, Akio Shigematsu, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Takahito Iwai, Junichi Sugita, Hitoshi Shibuya, Chikara Shimizu, Takanori Teshima
Biology of Blood and Marrow Transplantation, 24, 9, 1896, 1900, Elsevier Inc., 2018年, ［査読有り］
英語, 研究論文（学術雑誌）

Hepatitis C virus infection is an independent prognostic factor in follicular lymphoma
Joji Shimono, Hiroaki Miyoshi, Takeharu Kato, Takeshi Sugio, Kohta Miyawaki, Tomohiko Kamimura, Takuto Miyagishima, Tetsuya Eto, Yoshitaka Imaizumi, Koji Kato, Koji Nagafuji, Koichi Akashi, Masao Seto, Takanori Teshima, Koichi Ohshima
Oncotarget, 9, 2, 1717, 1725, Impact Journals LLC, 2018年, ［査読有り］
英語, 研究論文（学術雑誌）

脳死肝移植時のフィブリノゲン製剤使用による術中出血量と輸血使用量に関する検討
上床 貴代, 後藤 了一, 渡邊 千秋, 秋沢 宏次, 嶋村 剛, 清水 力, 豊嶋 崇徳, 早瀬 英子, 加畑 馨, 橋本 大吾, 伊藤 誠, 魚住 諒, 林 泰弘, 杉田 純一, 腰塚 靖之
日本輸血細胞治療学会誌, 64, 5, 641, 648, 一般社団法人 日本輸血・細胞治療学会, 2018年, ［査読有り］
日本語

Long-Lasting Graft-Derived Donor T Cells Contribute to the pathogenesis of Chronic Graft-versus-Host Disease in Mice
Mizuha Kosugi-Kanaya, Satoshi Ueha, Jun Abe, Shigeyuki Shichino, Francis H. W. Shand, Teppei Morikawa, Makoto Kurachi, Yusuke Shono, Naoto Sudo, Ai Yamashita, Fumiko Suenaga, Akihiro Yokoyama, Wang Yong, Masahiro Imamura, Takanori Teshima, Kouji Matsushima
FRONTIERS IN IMMUNOLOGY, 8, 8, 1842, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Clinicopathological features of primary splenic follicular lymphoma
Joji Shimono, Hiroaki Miyoshi, Tomohiko Kamimura, Tetsuya Eto, Takuto Miyagishima, Yuya Sasaki, Daisuke Kurita, Keisuke Kawamoto, Koji Nagafuji, Masao Seto, Takanori Teshima, Koichi Ohshima
ANNALS OF HEMATOLOGY, 96, 12, 2063, 2070, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Efficacy and prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma
Yutaka Tsutsumi, Chie Nakayama, Koki Kamada, Ryo Kikuchi, Daiki Kudo, Shinichi Ito, Satomi Matsuoka, Souichi Shiratori, Yoshiya Yamamoto, Hirohito Naruse, Takanori Teshima
ANNALS OF HEMATOLOGY, 96, 12, 2057, 2061, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: Evaluation of drug-drug interactions mediated by organic anion transporter 3
Katsuya Narumi, Yu Sato, Masaki Kobayashi, Ayako Furugen, Kumiko Kasashi, Takehiro Yamada, Takanori Teshima, Ken Iseki
BIOPHARMACEUTICS & DRUG DISPOSITION, 38, 9, 501, 508, 2017年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Transcriptome analysis reveals PDGF signaling-dependent regulation of myelofibrosis in murine chronic graft-versus-host diseases
Shigeyuki Shichino, Satoshi Ueha, Naoto Sudo, Mizuha Kosugi-Kanaya, Francis H. W. Shand, Teppei Morikawa, Shin-ichi Hashimoto, Takanori Teshima, Kouji Matsushima
CYTOKINE, 100, 108, 108, 2017年12月, ［査読有り］
英語

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

Quality of Life after Allogeneic Hematopoietic Cell Transplantation According to Affected Organ and Severity of Chronic Graft-versus-Host Disease
Saiko Kurosawa, Kumi Oshima, Takuhiro Yamaguchi, Atsumi Yanagisawa, Takahiro Fukuda, Heiwa Kanamori, Takehiko Mori, Satoshi Takahashi, Tadakazu Kondo, Akio Kohno, Koichi Miyamura, Yukari Umemoto, Takanori Teshima, Shuichi Taniguchi, Takuya Yamashita, Yoshihiro Inamoto, Yoshinobu Kanda, Shinichiro Okamoto, Yoshiko Atsuta
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 23, 10, 1749, 1758, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）

JAK阻害剤を用いたGVHD治療
豊嶋 崇徳
日本造血細胞移植学会雑誌, 6, 4, 146, 151, 2017年10月, ［査読有り］

GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia
S. Terakura, Y. Kuwatsuka, S. Yamasaki, A. Wake, J. Kanda, Y. Inamoto, S. Mizuta, T. Yamaguchi, N. Uchida, Y. Kouzai, N. Aotsuka, H. Ogawa, H. Kanamori, K. Nishiwaki, S. Miyakoshi, M. Onizuka, I. Amano, T. Fukuda, T. Ichinohe, Y. Atsuta, M. Murata, T. Teshima
BONE MARROW TRANSPLANTATION, 52, 9, 1261, 1267, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Clinicopathological analysis of primary splenic diffuse large B-cell lymphoma
Joji Shimono, Hiroaki Miyoshi, Junichi Kiyasu, Kensaku Sato, Tomohiko Kamimura, Tetsuya Eto, Takuto Miyagishima, Koji Nagafuji, Takanori Teshima, Koichi Ohshima
BRITISH JOURNAL OF HAEMATOLOGY, 178, 5, 719, 727, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）

IgA型ALアミロイドーシスに線状IgA皮膚症を併発した1例　　　　　　　　　　　　　　　
山口 泰之, 氏家 英之, 大東 寛幸, 岩田 浩明, 村松 憲, 清水 宏, 遠藤 知之, 豊嶋 崇徳
日本皮膚科学会雑誌, 127, 9, 2111, 2111, (公社)日本皮膚科学会, 2017年08月
日本語

北海道HIV福祉サービスネットワークの構築
富田 健一, 白坂 るみ, 遠藤 知之, 渡部 恵子, 武内 阿味, 坂本 玲子, センテノ田村 恵子, 石田 陽子, 豊嶋 崇徳
日本エイズ学会誌, 19, 3, 180, 184, (一社)日本エイズ学会, 2017年08月, ［査読有り］
日本語

Diffuse large B-cell lymphoma with a bulky mass in the cranial vault
Minoru Kanaya, Tomoyuki Endo, Daigo Hashimoto, Shogo Endo, Ryo Takemura, Kohei Okada, Kanako C. Hatanaka, Yoshihiro Matsuno, Takanori Teshima
INTERNATIONAL JOURNAL OF HEMATOLOGY, 106, 2, 147, 148, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images
Takahiro Tateno, Masahiro Onozawa, Junichi Hashiguchi, Takashi Ishio, Sayaka Yuzawa, Satomi Matsuoka, Mizuha Kosugi-Kanaya, Kohei Okada, Souichi Shiratori, Hideki Goto, Taichi Kimura, Junichi Sugita, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Shinya Tanaka, Satoshi Hashino, Takanori Teshima
TRANSPLANT INFECTIOUS DISEASE, 19, 4, e12720, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Inhibition of acute lethal pulmonary inflammation by the IDO-AhR pathway
Soung-Min Lee, Ha Young Park, Young-Sill Suh, Eun Hye Yoon, Juyang Kim, Won Hee Jang, Won-Sik Lee, Sae-Gwang Park, Il-Whan Choi, Inhak Choi, Sun-Woo Kang, Hwayoung Yun, Takanori Teshima, Byungsuk Kwon, Su-Kil Seo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114, 29, E5881, E5890, 2017年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation
Naohiro Miyashita, Tomoyuki Endo, Masahiro Onozawa, Daigo Hashimoto, Takeshi Kondo, Katsuya Fujimoto, Kaoru Kahata, Junichi Sugita, Hideki Goto, Toshihiro Matsukawa, Satoshi Hashino, Takanori Teshima
TRANSPLANT INFECTIOUS DISEASE, 19, 3, e12682, 2017年06月, ［査読有り］
英語, 研究論文（学術雑誌）

MALDI-TOF MS in post-transplant bloodstream infections: reliable identification of causative bacteria in the neutropenic phase
M. Kanaya, Y. Hayashi, D. Hashimoto, T. Endo, J. Sugita, H. Ohigashi, J. Hashiguchi, T. Matsukawa, S. Matsuoka, M. Kosugi-Kanaya, H. Goto, M. Onozawa, K. Kahata, K. Fujimoto, T. Kondo, K. Akizawa, H. Shibuya, C. Shimizu, T. Teshima
BONE MARROW TRANSPLANTATION, 52, 5, 778, 780, 2017年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Linear IgA Bullous Dermatosis Associated with Immunoglobulin Light-chain Amyloidosis
Yasuyuki Yamaguchi, Hideyuki Ujiie, Hiroyuki Ohigashi, Hiroaki Iwata, Ken Muramatsu, Tomoyuki Endou, Takanori Teshima, Hiroshi Shimizu
ACTA DERMATO-VENEREOLOGICA, 97, 4, 528, 529, 2017年04月, ［査読有り］
英語

Late onset toxic epidermal necrolysis induced by mogamulizumab, an anti-CC chemokine receptor 4 antibody for the treatment of adult T-cell leukaemia/lymphoma.
Souichi Shiratori, Hiroyuki Ohhigashi, Shinichi Ito, Kazuhiro Kudo, Maki Adachi, Toshiyuki Minamimoto, Junji Kato, Yasue Osai, Yutaka Tsutsumi, Takanori Teshima
Hematological oncology, 35, 1, 138, 140, 2017年03月, ［国際誌］
英語

Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation
J. Kanda, Y. Morishima, S. Terakura, A. Wake, N. Uchida, S. Takahashi, Y. Ono, Y. Onishi, H. Kanamori, N. Aotsuka, Y. Ozawa, H. Ogawa, T. Sakura, K. Ohashi, T. Ichinohe, K. Kato, Y. Atsuta, T. Teshima, M. Murata
LEUKEMIA, 31, 3, 663, 668, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes
Y-B Chen, T. Wang, M. T. Hemmer, C. Brady, D. R. Couriel, A. Alousi, J. Pidala, A. Urbano-Ispizua, S. W. Choi, T. Nishihori, T. Teshima, Y. Inamoto, B. Wirk, D. I. Marks, H. Abdel-Azim, L. Lehmann, L. Yu, M. Bitan, M. S. Cairo, M. Qayed, R. Salit, R. P. Gale, R. Martino, S. Jaglowski, A. Bajel, B. Savani, H. Frangoul, I. D. Lewis, J. Storek, M. Askar, M. A. Kharfan-Dabaja, M. Aljurf, O. Ringden, R. Reshef, R. F. Olsson, S. Hashmi, S. Seo, T. R. Spitzer, M. L. MacMillan, A. Lazaryan, S. R. Spellman, M. Arora, C. S. Cutler
BONE MARROW TRANSPLANTATION, 52, 3, 400, 408, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil
S. Terakura, A. Wake, Y. Inamoto, M. Murata, R. Sakai, T. Yamaguchi, S. Takahashi, N. Uchida, Y. Onishi, K. Ohashi, Y. Ozawa, H. Kanamori, H. Yamaguchi, T. Fukuda, T. Ichinohe, M. Takanashi, Y. Atsuta, T. Teshima
BONE MARROW TRANSPLANTATION, 52, 3, 423, 430, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）

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

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

Prior history of HLA-mismatched stem cell transplantation is a risk factor for graft failure in HLA-haploidentical transplantation
J. Sugita, T. Miyamoto, N. Kawashima, N. Hatsumi, N. Anzai, H. Kaneko, M. Nara, K. Minauchi, M. Harada, T. Teshima
BONE MARROW TRANSPLANTATION, 52, 2, 323, 325, 2017年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT
M. Murata, K. Ikegame, Y. Morishita, H. Ogawa, K. Kaida, H. Nakamae, T. Ikeda, T. Nishida, M. Inoue, T. Eto, K. Kubo, T. Sakura, T. Mori, N. Uchida, T. Ashida, Y. Matsuhashi, Y. Miyazaki, T. Ichinohe, Y. Atsuta, T. Teshima
Bone Marrow Transplant, 52, 2, 252, 257, 2017年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Unilateral conjunctival infiltration of Adult T-cell leukemia/lymphoma. Case report and literature review
Joji Shimono, Shigeki Kaino, Kohei Okada, Kazuo Oshimi, Yusuke Ishida, Tatsuro Takahashi, Takuto Miyagishima, Takanori Teshima
Journal of Clinical and Experimental Hematopathology, 57, 3, 143, 146, Japanese Society for Lymphoreticular Tissue Research, 2017年, ［査読有り］
研究論文（学術雑誌）

Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells
Mika Horiguchi, Mari Fujioka, Takeshi Kondo, Yoichiro Fujioka, Xinxin Li, Kosui Horiuchi, Aya O. Satoh, Prabha Nepal, Shinya Nishide, Asuka Nanbo, Takanori Teshima, Yusuke Ohba
CELL STRUCTURE AND FUNCTION, 42, 1, 15, 26, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical features of diffuse large B-cell lymphoma with polyploidy
Joji Shimono, Hiroaki Miyoshi, Masao Seto, Takanori Teshima, Koichi Ohshima
PATHOLOGY INTERNATIONAL, 67, 1, 17, 23, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord blood transplantation
Toshihiro Miyamoto, Shuichiro Takashima, Koji Kato, Ken Takase, Goichi Yoshimoto, Shuro Yoshida, Hideho Henzan, Koichi Osaki, Tomohiko Kamimura, Hiromi Iwasaki, Tetsuya Eto, Takanori Teshima, Koji Nagafuji, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 105, 1, 92, 99, 2017年01月, ［査読有り］
英語, 研究論文（学術雑誌）

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

日本骨髄バンクドナーの2回骨髄提供に関する検討
折原 勝己, 吾郷 浩厚, 奥山 美樹, 落合 亮一, 澤 正史, 田野﨑 隆二, 玉井 佳子, 豊嶋 崇徳, 中尾 康夫, 日野 雅之, 宮﨑 泰司, 神田 善伸, 金森 平和
日本造血細胞移植学会雑誌, 6, 2, 108, 114, (一社)日本造血細胞移植学会, 2017年, ［査読有り］
日本語, 研究論文（学術雑誌）

Ruxolitinib treatment for GvHD in patients with myelofibrosis
Y. Mori, K. Ikeda, T. Inomata, G. Yoshimoto, N. Fujii, H. Ago, T. Teshima
BONE MARROW TRANSPLANTATION, 51, 12, 1584, 1587, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups
Yoshihiro Inamoto, Fumihiko Kimura, Junya Kanda, Junichi Sugita, Kazuhiro Ikegame, Hideki Nakasone, Yasuhito Nannya, Naoyuki Uchida, Takahiro Fukuda, Kosuke Yoshioka, Yukiyasu Ozawa, Ichiro Kawano, Yoshiko Atsuta, Koji Kato, Tatsuo Ichinohe, Masami Inoue, Takanori Teshima
HAEMATOLOGICA, 101, 12, 1592, 1602, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Successful T-cell Replete Hematopoietic Stem Cell Boost Without Conditioning for Late Graft Failure
Y. Tsutsumi, T. Tateno, S. Ito, S. Shiratori, T. Teshima
TRANSPLANTATION PROCEEDINGS, 48, 9, 3225, 3226, 2016年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Evaluation of Short-Term Ruxolitinib Tapering Strategy Before Allogeneic Stem Cell Transplantation for Primary Myelofibrosis Through the Transition of Serum Cytokines and Growth Factors
Souichi Shiratori, Takahiro Tateno, Shinichi Ito, Yutaka Tsutsumi, Takanori Teshima
Transplantation Direct, 2, 8, e95, e95, Ovid Technologies (Wolters Kluwer Health), 2016年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD
Toshihiro Matsukawa, Daigo Hashimoto, Junichi Sugita, Seitarou Nakazawa, Takae Matsushita, Haruhiko Kashiwazaki, Hideki Goto, Masahiro Onozawa, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Yutaka Yamazaki, Takanori Teshima
INTERNATIONAL JOURNAL OF HEMATOLOGY, 104, 1, 117, 124, 2016年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Soluble DNAM-1, as a Predictive Biomarker for Acute Graft-Versus-Host Disease
Minoru Kanaya, Kazuko Shibuya, Rei Hirochika, Miyoko Kanemoto, Kazuteru Ohashi, Masafumi Okada, Yukiko Wagatsuma, Yukiko Cho, Hiroshi Kojima, Takanori Teshima, Masahiro Imamura, Hisashi Sakamaki, Akira Shibuya
PLOS ONE, 11, 6, e0154173, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation
Toshihiro Matsukawa, Kumi Izawa, Masamichi Isobe, Mariko Takahashi, Akie Maehara, Yoshinori Yamanishi, Ayako Kaitani, Ko Okumura, Takanori Teshima, Toshio Kitamura, Jiro Kitaura
GUT, 65, 5, 777, U777, 2016年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia
Y. Arai, T. Kondo, H. Yamazaki, K. Takenaka, J. Sugita, T. Kobayashi, Y. Ozawa, N. Uchida, K. Iwato, N. Kobayashi, Y. Takahashi, K. Ishiyama, T. Fukuda, T. Ichinohe, Y. Atsuta, T. Mori, T. Teshima, T. Japan, Society for, Hematopoietic Cell
Haematologica, 101, 5, 644, 652, 2016年05月, ［査読有り］
英語, 研究論文（学術雑誌）

HLA半合致移植の現状と展望
藤本勝也, 杉田純一, 豊嶋崇徳
臨床血液, 57, 3, 288, 297, 2016年04月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, HLA-haploidentical hematopoietic stem cell transplantation from related donors has gained attention as an alternative treatment for patients who do not have HLA-identical siblings and lack the time to search for HLA-matched unrelated donors due to availability for nearly all individuals. As a key factor in the success of this approach is depletion of donor T cells, HLA-haploidentical transplantation has rapidly gained acceptance worldwide with the development of three platforms: 1) CD34-positive cell selection using CliniMACS®; 2) the conditioning regimen with anti-thymocyte globulin; and 3) a recently-developed, post-transplant cyclophosphamide regimen. Since the high efficacy of T-cell-depletion provides both sufficient suppression of GVHD and a high risk of opportunistic infection, there is an urgent need to strengthen the prevention of viral infections. On the other hand, conditioning with ATG and the post-transplant cyclophosphamide regimen are becoming the strategies mainly used in haploidentical transplantation because of high practicability and low risk of infection, though these platforms necessitate other drugs for GVHD prophylaxis due to the low efficacy of T cell depletion. Together with progress in these platforms, outcomes of haploidentical transplantation are comparable to outcomes of HLA-matched transplants. Currently, HLA-haploidentical transplantation is increasingly being recognized as a novel breakthrough in hematopoietic stem cell transplantation.

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

Reprint of: Acute Graft-versus-Host Disease: Novel Biological Insights
Takanori Teshima, Pavan Reddy, Robert Zeiser
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 22, 3, S3, S8, 2016年03月, ［査読有り］
英語

Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia
Jun Aoki, Heiwa Kanamori, Masatsugu Tanaka, Satoshi Yamasaki, Takahiro Fukuda, Hiroyasu Ogawa, Koji Iwato, Kazuteru Ohashi, Hirokazu Okumura, Makoto Onizuka, Yoshitomo Maesako, Takanori Teshima, Naoki Kobayashi, Yasuo Morishima, Makoto Hirokawa, Yoshiko Atsuta, Shingo Yano, Akiyoshi Takami
AMERICAN JOURNAL OF HEMATOLOGY, 91, 3, 302, 307, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）

5-Azacytidine partially restores CD20 expression in follicular lymphoma that lost CD20 expression after rituximab treatment: A case report
Yutaka Tsutsumi, Hiroyuki Ohigashi, Shinichi Ito, Souichi Shiratori, Takanori Teshima
Journal of Medical Case Reports, 10, 1, 27, BioMed Central Ltd., 2016年02月02日, ［査読有り］
英語, 研究論文（学術雑誌）

オーバービュー
豊嶋 崇徳
臨床血液, 57, 3, 270, 270, 一般社団法人 日本血液学会, 2016年
日本語

Cord Blood Transplantation Following Reduced-intensity Conditioning for Adult-onset Inherited Hemophagocytic Lymphohistiocytosis
Takuro Kuriyama, Koji Kato, Keiji Sakamoto, Masayasu Hayashi, Shuichiro Takashima, Yasuo Mori, Katsuto Takenaka, Hiromi Iwasaki, Takanori Teshima, Naoki Harada, Koji Nagafuji, Toshihiro Miyamoto, Koichi Akashi
INTERNAL MEDICINE, 55, 6, 667, 671, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）

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

Determination of prognosis of Philadelphia chromosome-negative myeloproliferative neoplasms with a simple clinical examination: Retrospective analysis of 71 patients in a single institution
SHINICHI ITO, YUTAKA TSUTSUMI, HIROYUKI OHIGASHI, SOUICHI SHIRATORI, TAKANORI TESHIMA
Molecular and Clinical Oncology, 4, 1, 51, 57, Spandidos Publications, 2016年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF), are clonal hematopoietic diseases. A single-institution retrospective analysis was performed, including 71 MPN patients diagnosed at the Hakodate Municipal Hospital between April, 2001 and April, 2014, and certain clinical characteristics were identified as effective prognostic factors. The patients were categorized by risk factor scoring based on age, number of abnormal blood cell lineages and splenomegaly at diagnosis, and the association between this categorization and prognosis was analyzed using a statistical procedure. The effect of Janus kinase 2 (JAK2) V617F mutation on prognosis was also investigated. The MPN patients were consolidated into three risk groups based on the margin of intergroup survival differences: i) Score 1-2 (n=23), ii) score 3 (n=24) and iii) score 4-5 (n=24). MPN patients with scores of 4 or 5 exhibited poorer overall survival (OS) compared with those with lower scores (P<0.001). In addition, there were significant differences in event-free survival (EFS) among scoring groups (P=0.0059). PV and ET had a better prognosis compared with PMF, although this analysis suggested that PV and ET patients with scores of 4 or 5 may have a poorer prognosis in terms of OS (P=0.0052) and EFS (P=0.022) and should be closely followed up. We observed no significant prognostic effect of the JAK2V167F mutation for OS (P=0.28) or EFS (P=0.17). Our results suggested that a simple scoring system based on age, blood cell counts and presence of splenomegaly at diagnosis may be used for the long-term prognosis of MPN patients.

Unplanned discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia
YUTAKA TSUTSUMI, SHINICHI ITO, HIROYUKI OHIGASHI, SOUICHI SHIRATORI, TAKANORI TESHIMA
Molecular and Clinical Oncology, 4, 1, 89, 92, Spandidos Publications, 2016年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, This study was conducted to investigate the outcomes of patients with chronic myeloid leukemia (CML) who discontinued tyrosine kinase inhibitor (TKI) treatment. A single-center retrospective analysis was performed, including 46 chronic-phase (CP) CML patients who achieved complete molecular response (CMR) with TKIs. TKI treatment was discontinued in 13 patients based on their requests. The BCR-ABL transcript levels were monitored in the peripheral blood by quantitative polymerase chain reaction analysis following treatment discontinuation. Of the 13 patients who discontinued TKI treatment, 7 remained in CMR, with a median follow-up of 26 months (range, 10-60 months). The remaining 6 patients lost CMR following TKI discontinuation; 2 of these patients achieved a second CMR following re-administration of TKIs, 2 patients spontaneously achieved CMR and 2 remained in complete hematological response (CHR) without TKI treatment with a median follow-up of 29.5 months (range, 10-52 months). In conclusion, the survival of patients who lost CMR following TKI discontinuation may not be affected, even without re-administration of TKIs. Vigilant observation is recommended for such patients. The limitations of this study included the small patient sample, retrospective design and patient heterogeneity. Therefore, the results must be interpreted with caution.

Pharmacokinetics and dose adjustment of etoposide administered in a medium-dose etoposide, cyclophosphamide and total body irradiation regimen before allogeneic hematopoietic stem cell transplantation.
Yuki Tazawa, Akio Shigematsu, Kumiko Kasashi, Junichi Sugita, Tomoyuki Endo, Takeshi Kondo, Takanori Teshima, Ken Iseki, Mitsuru Sugawara, Yoh Takekuma
Journal of pharmaceutical health care and sciences, 2, 18, 18, 18, 2016年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: We investigated the pharmacokinetics of etoposide (ETP) to reduce the inter-individual variations of ETP concentrations in patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation. We also carried out an in vivo study using rats to verify the dose adjustment. METHODS: This study included 20 adult patients. ETP was administered intravenously at a dose of 15 mg/kg once daily for 2 days (total dose: 30 mg/kg) combined with standard conditioning of cyclophosphamide and total body irradiation. In an in vivo study using rats, ETP was administered intravenously at a dose of 15 mg/kg or an adjusted dose. The ETP plasma concentration was determined by using HPLC. The pharmacokinetic parameters were estimated by using a 1-compartment model. RESULTS: The peak concentration (Cmax) of ETP and the area under the plasma concentration-time curve (AUC) of ETP differed greatly among patients (range of Cmax, 51.8 - 116.5 μg/mL; range of AUC, 870 - 2015 μg · h/mL). A significant relationship was found between Cmax and AUC (R = 0.85, P < 0.05). Distribution volume (Vd) was suggested to be one of the factors of inter-individual variation in plasma concentration of ETP in patients (range of Vd, 0.13 - 0.27 L/kg), and correlated with Alb and body weight (R = 0.56, P < 0.05; R = 0.40, P < 0.05 respectively). We predicted Vd of rats by body weight of rats (with normal albumin levels and renal function), and the dose of ETP was adjusted using predicted Vd. In the dose adjustment group, the target plasma ETP concentration was achieved and the variation of plasma ETP concentration was decreased. CONCLUSION: The results suggested that inter-individual variation of plasma concentration of ETP could be reduced by predicting Vd. Prediction of Vd is effective for reducing individual variation of ETP concentration and might enable a good therapeutic effect to be achieved.

組織幹細胞システム保護による次世代型造血幹細胞移植　　　　　　　　　　　　　　　
豊嶋 崇徳
上原記念生命科学財団研究報告集, 29, 1, 4, (公財)上原記念生命科学財団, 2015年12月
日本語

Effects of conditioning intensity in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia
Shuichiro Takashima, Toshihiro Miyamoto, Tomohiko Kamimura, Goichi Yoshimoto, Shuro Yoshida, Hideho Henzan, Ken Takase, Koji Kato, Yoshikiyo Ito, Yuju Ohno, Koji Nagafuji, Tetsuya Eto, Takanori Teshima, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 102, 6, 689, 696, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Occurrence of adverse events caused by valganciclovir as pre-emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low-dose administration
M. Takahata, S. Hashino, M. Nishio, J. Sugita, A. Shigematsu, M. Onozawa, K. Fujimoto, T. Endo, T. Kondo, J. Tanaka, M. Imamura, T. Teshima
TRANSPLANT INFECTIOUS DISEASE, 17, 6, 810, 815, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Sustained CD4 and CD8 lymphopenia after rituximab maintenance therapy following bendamustine and rituximab combination therapy for lymphoma
Yutaka Tsutsumi, Shinichi Ito, Hiroyuki Ohigashi, Naohiro Miyashita, Joji Shimono, Souichi Shiratori, Takanori Teshima
LEUKEMIA & LYMPHOMA, 56, 11, 3216, 3218, 2015年11月, ［査読有り］
英語

Decreased secretion of Paneth cell α-defensins in graft-versus-host disease
Y. Eriguchi, K. Nakamura, D. Hashimoto, S. Shimoda, N. Shimono, K. Akashi, T. Ayabe, T. Teshima
Transplant Infectious Disease, 17, 5, 702, 706, 2015年10月01日
英語, 研究論文（学術雑誌）

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia
Yoshihiro Inamoto, Mary E. D. Flowers, Tao Wang, Alvaro Urbano-Ispizua, Michael T. Hemmer, Corey S. Cutler, Daniel R. Couriel, Amin M. Alousi, Joseph H. Antin, Robert Peter Gale, Vikas Gupta, Betty K. Hamilton, Mohamed A. Kharfan-Dabaja, David I. Marks, Olle T. H. Ringden, Gerard Socie, Melhem M. Solh, Goerguen Akpek, Mitchell S. Cairo, Nelson J. Chao, Robert J. Hayashi, Taiga Nishihori, Ran Reshef, Ayman Saad, Ami Shah, Takanori Teshima, Martin S. Tallman, Baldeep Wirk, Stephen R. Spellman, Mukta Arora, Paul J. Martin
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 21, 10, 1776, 1782, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning
Junichi Sugita, Naomi Kawashima, Tomoaki Fujisaki, Kazuhiko Kakihana, Shuichi Ota, Keitaro Matsuo, Toshihiro Miyamoto, Koichi Akashi, Shuichi Taniguchi, Mine Harada, Takanori Teshima
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 21, 9, 1646, 1652, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Preserved in vivo reconstitution ability of PBSCs cryopreserved for a decade at -80 °C.
Shima T, Iwasaki H, Yamauchi T, Kadowaki M, Kiyosuke M, Mochimaru T, Takenaka K, Miyamoto T, Akashi K, Teshima T
Bone Marrow Transplant., 50, 9, 1195, 1200, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know
M. Ogata, T. Fukuda, T. Teshima
BONE MARROW TRANSPLANTATION, 50, 8, 1030, 1036, 2015年08月
英語

Ultrasonographic evaluation of gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation
Mutsumi Nishida, Akio Shigematsu, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Takahito Iwai, Tomoyuki Endo, Akihiro Iguchi, Hitoshi Shibuya, Kanako Hatanaka, Chikara Shimizu, Takanori Teshima
CLINICAL TRANSPLANTATION, 29, 8, 697, 704, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）

PolyI:C-Induced, TLR3/RIP3-Dependent Necroptosis Backs Up Immune Effector-Mediated Tumor Elimination In Vivo
Ryo Takemura, Hiromi Takaki, Seiji Okada, Hiroaki Shime, Takashi Akazawa, Hiroyuki Oshiumi, Misako Matsumoto, Takanori Teshima, Tsukasa Seya
CANCER IMMUNOLOGY RESEARCH, 3, 8, 902, 914, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Late onset toxic epidermal necrolysis induced by mogamulizumab, an anti-CC chemokine receptor 4 antibody for the treatment of adult T-cell leukaemia/lymphoma.
Shiratori S, Ohigashi H, Ito S, Kudo K, Adachi M, Minamimoto T, Kato J, Osai Y, Tsutsumi Y, Teshima T
Hematol Oncol., 2015年07月, ［査読有り］

Decreased secretion of Paneth cell α-defensin in graft-versus-host disease.
Eriguchi Y, Nakamura K, Hashimoto D, Shimoda S, Shimono N, Akashi K, Ayabe T, Teshima T
Transpl Infect Dis., 2015年07月, ［査読有り］

初発の非胚中心B細胞様びまん性大細胞型B細胞性リンパ腫患者を対象としたブルトン型チロシンキナーゼ(BTK)阻害薬PCI-32765(ibrutinib)の国際共同第III相試験
頼 晋也, 豊嶋 崇徳, 福原 規子, 飛内 賢正, 畠 清彦, 下山 達, 安藤 潔, 内田 俊樹, 永井 宏和, 谷脇 雅史, 柴山 浩彦, 中前 博久, 松村 到, 石川 隆之, 一戸 辰夫, 加藤 光次, 日高 道弘
日本リンパ網内系学会会誌, 55, 108, 108, (一社)日本リンパ網内系学会, 2015年06月, ［査読有り］
日本語

JAK阻害剤によるGVHDの制御
豊嶋崇徳
血液内科, 70, 5, 656, 660, 科学評論社, 2015年05月, ［査読有り］
日本語

Upregulation of microRNA-126-5p is associated with drug resistance to cytarabine and poor prognosis in AML patients
YOSHIHIKO SHIBAYAMA, TAKESHI KONDO, HIROKI OHYA, SHIN-ICHI FUJISAWA, TAKANORI TESHIMA, KEN ISEKI
Oncology Reports, 33, 5, 2176, 2182, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.
Youko Suehiro, Atsuhiko Hasegawa, Tadafumi Iino, Amane Sasada, Nobukazu Watanabe, Masao Matsuoka, Ayako Takamori, Ryuji Tanosaki, Atae Utsunomiya, Ilseung Choi, Tetsuya Fukuda, Osamu Miura, Shigeo Takaishi, Takanori Teshima, Koichi Akashi, Mari Kannagi, Naokuni Uike, Jun Okamura
Br. J. Haematol., 169, 3, 356, 367, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）

α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.
Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T
Blood., 125, 19, 3014, 3023, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）

The primacy of IL-6 in IPS?
Takanori Teshima
Blood, 125, 15, 2320, 2322, 2015年04月09日, ［査読有り］
研究論文（学術雑誌）

Impact of conditioning intensity and TBI on acute GVHD after hematopoietic cell transplantation
H. Nakasone, T. Fukuda, J. Kanda, T. Mori, S. Yano, T. Kobayashi, K. Miyamura, T. Eto, H. Kanamori, K. Iwato, N. Uchida, S. Mori, T. Nagamura-Inoue, T. Ichinohe, Y. Atsuta, T. Teshima, M. Murata
BONE MARROW TRANSPLANTATION, 50, 4, 559, 565, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Analysis of the influence of dabigatran on coagulation factors and inhibitors
Y. Tsutsumi, J. Shimono, H. Ohhigashi, S. Ito, S. Shiratori, T. Teshima
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 37, 2, 225, 230, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）

CD155 Regulates Regulatory T Cell Population and Attenuates Acute Graft-Versus-Host Disease
Minoru Kanaya, Kazuko Shibuya, Fumie Abe, Takanori Teshima, Akira Shibuya
Biology of Blood and Marrow Transplantation, 21, 2, S335, S335, Elsevier BV, 2015年02月, ［査読有り］
研究論文（学術雑誌）

Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation.
Matsukawa T, Izawa K, Isobe M, Takahashi M, Maehara A, Yamanishi Y, Kaitani A, Okumura K, Teshima T, Kitamura T, Kitaura J
Gut., 2015年02月, ［査読有り］

Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research
Sally Arai, Mukta Arora, Tao Wang, Stephen R. Spellman, Wensheng He, Daniel R. Courie, Alvaro Urbano-Ispizua, Corey S. Cutler, Andrea A. Bacigalupo, Minoo Battiwallaw, Mary E. Flowers, Mark B. Juckett, Stephanie J. Lee, Alison W. Loren, Thomas R. Klumpp, Susan E. Prockup, Olle E. T. H. Ringden, Bipin N. Savani, Gerard Socie, Kirk R. Schultz, Thomas Spitzer, Takanori Teshima, Christopher N. Bredeson, David A. Jacobsohn, Robert J. Hayashi, William R. Drobyski, Haydar A. Frangoul, Gorgiin Akpek, Vincent T. Ho, Victor A. Lewis, Robert Peter Gale, John Koreth, Nelson J. Chao, Mahmoud D. Aljurf, Brenda W. Cooper, Mary J. Laughlin, Jack W. Hsu, Peiman Hematti, Leo F. Verdonck, Melhelm M. Solh, Maxim Norkin, Vijay Reddy, Jose A. Perez-Simon, Nandita Khera, Ian D. Lewis, Yoshiko Atsuta, Richard F. Olsson, Wael Saber, Edmund K. Waller, Didier Blaise, Joseph A. Pidala, Paul J. Martin, Prakash Satwani, Martin Bornhauser, Yoshihiro Inamoto, Daniel J. Weisdorf, Mary M. Horowitz, Steven Z. Pavletic
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 21, 2, 266, 274, 2015年02月, ［査読有り］
英語, 研究論文（学術雑誌）

血液腫瘍治療薬.　　　　　　　　　　　　　　　
藤本勝也, 豊嶋崇徳
医薬ジャーナル増刊号「新薬展望2015」, 51, S-1, 180, 189, 2015年

移植後シクロホスファミドを用いたHLA半合致移植の現状と課題.
杉田純一, 小杉瑞葉, 豊嶋崇徳
日本造血細胞移植学会雑誌, 4, 1, 9, 22, The Japan Society for Hematopoietic Stem Cell Transplantation, 2015年01月
英語, 研究論文（学術雑誌）, 近年，移植後シクロホスファミドを用いたhuman leukocyte antigen（HLA）半合致骨髄移植において，良好な生着とgraft-versus-host disease（GVHD）抑制効果が得られることが示された。その機序として，選択的にアロ応答性T細胞を排除すること，制御性T細胞を温存することが考えられている。GVHD，非再発死亡は低いが，再発率が高い点が問題であり，再発率の低下や拒絶の減少を目的として，末梢血幹細胞や骨髄破壊的前処置を用いた移植において本法が試みられている。さらに移植後シクロホスファミドは血液悪性疾患のみならず非腫瘍性血液疾患に対する同種移植後にも適用されている。近年ではHLA一致移植への使用も報告され，カルシニューリン阻害剤を使用しない新たなGVHD予防法のプラットフォームとして期待される。

抗がん剤の副作用と支持療法-より適切な抗がん剤の安全使用をめざして-　　　　　　　　　　　　　　　
小野澤真弘, 豊嶋崇徳
日本臨床, 73, suppl2, 623, 627, 2015年

非血縁者間同種末梢血幹細胞移植の今後の展開.　　　　　　　　　　　　　　　
重松明男, 豊嶋崇徳
医学のあゆみ, 253, 2, 187, 188, 2015年

造血幹細胞移植における腸幹細胞、ニッチシステムと腸内細菌.無菌生物　　　　　　　　　　　　　　　
豊嶋 崇徳
無菌生物, 45, 1, 43, 47, 日本無菌生物ノートバイオロジー学会, 2015年
日本語

腸内細菌叢がGVHDにもたらす影響　　　　　　　　　　　　　　　
早瀬英子, 豊嶋崇徳
Keynote R・A : rheumatic & autoimmune diseases, 3, 1, 24, 28, 2015年01月

白血病・リンパ腫の治療：過去から未来へ　　　　　　　　　　　　　　　
豊嶋 崇徳
北海道医報, 1156, 1, 31, 35, 2015年01月

CD4/CD8 Double-negative T-cell Lymphoma: A Variant of Primary Cutaneous CD8(+) Aggressive Epidermotropic Cytotoxic T-cell Lymphoma?
Toshinari Miyauchi, Riichiro Abe, Yusuke Morita, Maki Adachi, Keiko Shiba, Yohei Hamade, Nan Saito, Machiko Nishimura, Makoto Ibata, Kohei Okada, Akio Shigematsu, Tomoyuki Endo, Kazuhiro Kawai, Takanori Teshima, Hiroshi Shimizu
ACTA DERMATO-VENEREOLOGICA, 95, 8, 1024, 1025, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）

Human Herpesvirus-6 Pneumonitis around the Engraftment of Cord Blood Transplantation following Foscarnet Prophylaxis in a Patient with Acute Leukemia
Takashi Ishio, Tomoyuki Endo, Kohei Okada, Akio Shigematsu, Satoshi Hashino, Takanori Teshima
Case Reports in Hematology, 2015, 1, 5, Hindawi Limited, 2015年, ［査読有り］
研究論文（学術雑誌）, Human herpesvirus-6 (HHV-6) reactivation is sometimes observed in immunocompromised patients, especially after allogeneic stem cell transplantation. The complications of HHV-6 reactivation in this setting are mainly recognized as HHV-6 encephalitis. We herein report the case of a patient who developed HHV-6 pneumonitis after cord blood transplantation (CBT). A 35-year-old male underwent CBT for T-cell/myeloid mixed phenotype acute leukemia and achieved neutrophil engraftment on day 31. He had received foscarnet as prophylaxis for HHV-6 reactivation. A computed tomography (CT) scan to evaluate the leukemic tumor showed bilateral interstitial pneumonitis on day 33, although he had no respiratory symptoms. The findings of the CT scan were consistent with those of HHV-6 pneumonitis that were reported previously. HHV-6 DNA, but no other pathogens, was detected in his bronchoalveolar lavage (BAL) fluid. The patient was successfully treated with a therapeutic dose of foscarnet. This case indicates that performing a CT scan around the time of neutrophil engraftment can play an important role in detecting the early phase of HHV-6 pneumonia, and BAL should be considered if features consistent with HHV-6 pneumonitis are observed in patients with a risk of HHV-6 reactivation.

当院におけるHIV 感染者のビタミンDの検討
遠藤知之, 藤本勝也, 南昭子, 吉田美穂, 竹村龍, 渡部恵子, 坂本玲子, 武内阿味, 近藤健, 橋野聡, 清水力, 豊嶋崇徳
日本エイズ学会誌, 17, 1, 30, 35, (一社)日本エイズ学会, 2015年, ［査読有り］
日本語

Primary Bone Lymphoma: A Clinical Analysis of 17 Patients in a Single Institution
Eiko Hayase, Mitsutoshi Kurosawa, Hiroaki Suzuki, Kohei Kasahara, Tomohiro Yamakawa, Masakatsu Yonezumi, Sachiko Suzuki, Takanori Teshima
ACTA HAEMATOLOGICA, 134, 2, 80, 85, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）

Ultra-high level of serum soluble interleukin-2 receptor at diagnosis predicts poor outcome for angioimmunoblastic T-cell lymphoma
Souichi Shiratori, Mizuha Kosugi-Kanaya, Akio Shigematsu, Hajime Kobayashi, Satoshi Yamamoto, Naoki Kobayashi, Hiroshi Iwasaki, Akio Mori, Yasuyuki Kunieda, Yutaka Tsutsumi, Mitsutoshi Kurosawa, Yasutaka Kakinoki, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Takanori Teshima
LEUKEMIA & LYMPHOMA, 56, 9, 2592, 2597, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）

PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+T cell response to autologous survivin in HLA-A*2402 transgenic mice
Jun Kasamatsu, Shojiro Takahashi, Masahiro Azuma, Misako Matsumoto, Akiko Morii-Sakai, Masahiro Imamura, Takanori Teshima, Akari Takahashi, Yoshihiko Hirohashi, Toshihiko Torigoe, Noriyuki Sato, Tsukasa Seya
IMMUNOBIOLOGY, 220, 1, 74, 82, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome
M. J. Lechowicz, H. M. Lazarus, J. Carreras, G. G. Laport, C. S. Cutler, P. H. Wiernik, G. A. Hale, D. Maharaj, R. P. Gale, P. A. Rowlings, C. O. Freytes, A. M. Miller, J. M. Vose, R. T. Maziarz, S. Montoto, D. G. Maloney, P. N. Hari
BONE MARROW TRANSPLANTATION, 49, 11, 1360, 1365, 2014年11月, ［査読有り］
英語, 研究論文（学術雑誌）

[Case Report; Primary central nervous system lymphoma mimicking progressive multifocal leukoencephalopathy in a patient with acquired immune deficiency syndrome].
Yamakawa T, Fujimoto K, Ebata K, Iwasaki J, Takahashi S, Shiratori S, Sugita J, Kondo T, Nishio M, Teshima T
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 103, 10, 2578, 2580, 2014年10月, ［査読有り］

Hepatitis B virus (HBV) reverse seroconversion (RS) can be prevented even in non-responders to hepatitis B vaccine after allogeneic stem cell transplantation: long-term analysis of intervention in RS with vaccine for patients with previous HBV infection
M. Takahata, S. Hashino, M. Onozawa, A. Shigematsu, J. Sugita, K. Fujimoto, T. Endo, T. Kondo, J. Tanaka, M. Imamura, T. Teshima
TRANSPLANT INFECTIOUS DISEASE, 16, 5, 797, 801, 2014年10月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Essential requirements for setting up a stem cell processing laboratory
T. Leemhuis, D. Padley, C. Keever-Taylor, D. Niederwieser, T. Teshima, F. Lanza, C. Chabannon, P. Szabolcs, A. Bazarbachi, M. B. C. Koh
BONE MARROW TRANSPLANTATION, 49, 8, 1098, 1105, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a consolidation therapy after autologous stem cell transplantation for symptomatic multiple myeloma in Japanese patients
Shuichiro Takashima, Toshihiro Miyamoto, Masanori Kadowaki, Yoshikiyo Ito, Takatoshi Aoki, Ken Takase, Takahiro Shima, Goichi Yoshimoto, Koji Kato, Tsuyoshi Muta, Motoaki Shiratsuchi, Katsuto Takenaka, Hiromi Iwasaki, Takanori Teshima, Tomohiko Kamimura, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 100, 2, 159, 164, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）

チゲサイクリンとコリスチンの併用が奏功した多剤耐性アシネトバクター・バウマニによるカテーテル関連血流感染症の1例　　　　　　　　　　　　　　　
山田武宏, 白鳥聡一, 杉田純一, 藤本勝也, 豊嶋崇徳, 福元達也, 岩崎澄央, 秋沢宏治
日本化学療法学会雑誌, 62, 4, 501, 505, (公社)日本化学療法学会, 2014年07月, ［査読有り］
日本語

JAK inhibitors: a home run for GVHD patients?
Takanori Teshima
Blood, 123, 24, 3691, 3693, 2014年06月12日, ［査読有り］
研究論文（学術雑誌）

High Level of Serum Soluble Interleukin-2 Receptor at Transplantation Predicts Poor Outcome of Allogeneic Stem Cell Transplantation for Adult T Cell Leukemia
Akio Shigematsu, Naoki Kobayashi, Hiroshi Yasui, Motohiro Shindo, Yasutaka Kakinoki, Kyuhei Koda, Satoshi Iyama, Hiroyuki Kuroda, Yutaka Tsutsumi, Masahiro Imamura, Takanori Teshima
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 20, 6, 801, 805, 2014年06月, ［査読有り］
英語, 研究論文（学術雑誌）

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

臍帯血移植における移植片対宿主病(GVHD)　　　　　　　　　　　　　　　
高畑むつみ, 豊嶋崇徳
医学のあゆみ, 249, 7, 587, 592, 2014年05月

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

Comparison of bortezomib, cyclophosphamide, and dexamethasone (VCD) induction with bortezomib and dexamethasone (BD) induction for newly diagnosed symptomatic multiple myeloma
Takashima S, Miyamoto T, Kamimura T, Yoshimoto G, Kato K, Ito Y, Muta T, Matsushima T, Shiratsuchi M, Tanimoto K, Takenaka K, Iwasaki H, Teshima T, Akashi K
International Journal of Myeloma, 4, 1, 7, 12, 2014年03月, ［査読有り］

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

移植後GVHDの分子病態と治療
豊嶋 崇徳
血液内科, 68, 3, 291, 297, 2014年03月

ビンクリスチンによる麻痺性イレウスに引き続き posterior reversible encephalopathy syndrome を発症したT細胞性リンパ芽球性リンパ腫
早瀬英子, 杉田純一, 藤本勝也, 江端浩, 山川知宏, 吉田美穂, 竹村龍, 岩﨑純子
臨床血液, 55, 2, 249, 253, (一社)日本血液学会-東京事務局, 2014年02月, ［査読有り］
日本語

北海道内のHIV感染症患者におけるHBV・HCV重複感染の現状 -拠点病院・診療施設アンケート調査結果-
藤本勝也, 遠藤知之, 吉田美穂, 竹村龍, 近藤健, 橋野聡, 須田剛生, 中馬誠, 後藤了一, センテノ田村恵子, 渡部恵子, 大野稔子, 石田禎夫, 大竹孝明, 宮城島拓人, 小林一, 堤豊, 三宅高義, 北川浩彦, 佐藤典宏, 豊嶋崇徳
日本エイズ学会誌, 16, 1, 18, 27, (一社)日本エイズ学会, 2014年02月, ［査読有り］
日本語

Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease
Haruko Sugiyama, Yoshinobu Maeda, Hisakazu Nishimori, Yoshiko Yamasuji, Ken-ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Katsuji Shinagawa, Takehiro Tanaka, Kengo Takeuchi, Takanori Teshima, Mitsune Tanimoto
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 20, 2, 183, 191, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）

“No effect of humanized CCR monoclonal antibody (Mogamulizumab) on treatment-resistant adult T-cell leukemia with meningeal infiltration.”
Tsutsumi Y, Shimono J, Miyashita N, Teshima T
Leuk Lymphoma (letter), 55, 2, 457, 459, 2014年02月, ［査読有り］
英語

[Control of graft-versus-host disease].
Sugita J, Teshima T
[Rinsho ketsueki] The Japanese journal of clinical hematology, 55, 2, 170, 176, 2, 2014年02月, ［査読有り］
日本語

[Posterior reversible encephalopathy syndrome following paralytic ileus caused by vincristine in a patient with T cell lymphoblastic lymphoma].
Eiko Hayase, Junichi Sugita, Katsuya Fujimoto, Ko Ebata, Tomohiro Yamakawa, Miho Yoshida, Ryo Takemura, Junko Iwasaki, Shojiro Takahashi, Souichi Shiratori, Takeshi Kondo, Junji Tanaka, Takanori Teshima
[Rinsho ketsueki] The Japanese journal of clinical hematology, 55, 2, 249, 53, 2014年02月, ［国内誌］
日本語, 研究論文（学術雑誌）, A 22-year-old woman presented with high fever, chest tightness and cough in January 20XX. Since CT scans revealed an anterior mediastinal mass, percutaneous needle biopsies of the mass were performed and she was diagnosed with T-cell lymphoblastic lymphoma (T-LBL). After the immunophenotype of lymphocytes in her pleural effusion had been identified, she received CHOP therapy because her dyspnea worsened, and induction therapy for acute lymphoblastic leukemia was subsequently performed after confirmation of her diagnosis as T-LBL. During this induction therapy, she developed paralytic ileus. One week thereafter, she suddenly exhibited visual disturbance, headache and nausea. Her cerebrospinal fluid was normal. Magnetic resonance imaging showed symmetrical high signal intensities on T2-weighted and fluid-attenuated inversion recovery images, and low signal intensities on T1-weighted images in the cortical and subcortical white matter of the posterior parietal and occipital lobes. Based on these findings, she was diagnosed as having posterior reversible encephalopathy syndrome (PRES). During chemotherapy for hematologic malignancies, some patients with PRES reportedly develop paralytic ileus or tumor lysis syndrome. PRES should be considered in patients with neurological abnormalities following such complications during chemotherapy.

Graft-versus-host disease制御
杉田純一, 豊嶋崇徳
臨床血液, 55, 2, 170, 176, 2014年02月

Impact of Conditioning Intensity with or without Total Body Irradiation on Acute Graft-Versus-Host Disease and Clinical Outcomes
Hideki Nakasone, Takahiro Fukuda, Junya Kanda, Takehiko Mori, Takanori Teshima, Shingo Yano, Naoyuki Uchida, Kazuhiko Kakihana, Tetsuya Eto, Shin-Ichiro Mori, Tokiko Nagamura, Tatsuo Ichinohe, Yoshiko Atsuta, Makoto Murata
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 20, 2, S275, S276, 2014年02月
英語, 研究論文（学術雑誌）

Epstein-Barr Virus-Associated Smooth Muscle Tumors After Bone Marrow Transplantation
Eiko Hayase, Katsuya Fujimoto, Tomoko Mitsuhashi, Yutaka Hatanaka, Miho Yoshida, Ryo Takemura, Junko Iwasaki, Souichi Shiratori, Junichi Sugita, Takeshi Kondo, Junji Tanaka, Masahiro Imamura, Yoshihiro Matsuno, Takanori Teshima
TRANSPLANTATION, 97, 1, E1, +, 2014年01月, ［査読有り］
英語

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

Effect of combination therapy of tigecycline and colistin against a case of catheter-related bloodstream infection by multidrug-resistant Acinetobacter baumannii　　　　　　　　　　　　　　　
Takehiro Yamada, Souichi Shiratori, Junichi Sugita, Katsuya Fujimoto, Takanori Teshima, Tatsuya Fukumoto, Sumio Iwasaki, Koji Akizawa, Katsuya Narumi, Nobuhisa Ishiguro, Ken Iseki
Japanese Journal of Chemotherapy, 62, 4, 501, 505, Japan Society of Chemotherapy, 2014年
日本語, 研究論文（学術雑誌）

消化管GVHD（graft-versus-host disease）に対する経口ベクロメタゾン製剤の有用性の検討
久保田 康生, 鳴海 克哉, 笠師 久美子, 山田 武宏, 岡田 耕平, 重松 明男, 豊嶋 崇徳, 井関 健
医療薬学, 40, 5, 291, 296, 一般社団法人日本医療薬学会, 2014年
日本語

The Use of Oral Beclomethasone Dipropionate in the Treatment of Gastrointestinal Graft-versus-host Disease: The Experience of the Fukuoka Blood and Marrow Transplantation (BMT) Group
Shuichiro Takashima, Tetsuya Eto, Motoaki Shiratsuchi, Michihiro Hidaka, Yasuo Mori, Koji Kato, Kenjiro Kamezaki, Seido Oku, Hideho Henzan, Ken Takase, Takamitsu Matsushima, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Koichi Akashi, Takanori Teshima
INTERNAL MEDICINE, 53, 12, 1315, 1320, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）

Successful Treatment of Invasive Zygomycosis Based on a Prompt Diagnosis Using Molecular Methods in a Patient with Acute Myelogenous Leukemia
Junichiro Yuda, Koji Kato, Yoshikane Kikushige, Kiyofumi Ohkusu, Makiko Kiyosuke, Keiji Sakamoto, Seido Oku, Noriko Miyake, Masako Kadowaki, Tadafumi Iino, Kazuki Tanimoto, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Nobuyuki Shimono, Takanori Teshima, Koichi Akashi
INTERNAL MEDICINE, 53, 10, 1087, 1091, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）

Hepatitis B virus reactivation with rituximab-containing regimen
Yutaka Tsutsumi, Yoshiya Yamamoto, Joji Shimono, Hiroyuki Ohhigashi, Takanori Teshima
World Journal of Hepatology, 5, 11, 612, 620, 2013年11月
英語

Reduced-intensity conditioning followed by cord blood transplantation in a patient with refractory folliculotropic mycosis fungoides
Takashi Nakaike, Koji Kato, Seido Oku, Masayasu Hayashi, Yoshikane Kikushige, Mika Kuroiwa, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Takanori Teshima, Koichi Ohshima, Koichi Akashi
International Journal of Hematology, 98, 4, 491, 495, 2013年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical outcomes of allogeneic stem cell transplantation for relapsed or refractory follicular lymphoma: A retrospective analysis by the Fukuoka Blood and Marrow Transplantation Group
Yoshikiyo Ito, Toshihiro Miyamoto, Tomohiko Kamimura, Ken Takase, Hideho Henzan, Yasuo Sugio, Koji Kato, Yuju Ohno, Tetsuya Eto, Takanori Teshima, Koichi Akashi
International Journal of Hematology, 98, 4, 463, 471, 2013年10月, ［査読有り］
英語, 研究論文（学術雑誌）

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

抗癌剤治療をしている患者さんへのインフルエンザワクチン接種について教えて下さい　　　　　　　　　　　　　　　
藤本勝也, 豊嶋崇徳
インフルエンザ, 14, 3, 32, 2013年10月

基礎・臨床医学融合の最前線としての造血幹細胞移植　　　　　　　　　　　　　　　
豊嶋 崇徳
細胞, 45, 11, 2, 4, 2013年10月

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

Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration
Kazutoshi Aoyama, Asim Saha, Jakub Tolar, Megan J. Riddle, Rachelle G. Veenstra, Patricia A. Taylor, Rune Blomhoff, Angela Panoskaltsis-Mortari, Christopher A. Klebanoff, Gerard Socie, David H. Munn, William J. Murphy, Jonathan S. Serody, LeShara M. Fulton, Takanori Teshima, Roshantha A. Chandraratna, Ethan Dmitrovsky, Yanxia Guo, Randolph J. Noelle, Bruce R. Blazar
BLOOD, 122, 12, 2125, 2134, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma
Toshihiro Miyamoto, Goichi Yoshimoto, Tomohiko Kamimura, Tsuyoshi Muta, Shuichiro Takashima, Yoshikiyo Ito, Motoaki Shiratsuchi, Ilseung Choi, Koji Kato, Katsuto Takenaka, Hiromi Iwasaki, Yasushi Takamatsu, Takanori Teshima, Koichi Akashi
International Journal of Hematology, 98, 3, 337, 345, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Evaluating the association between histological manifestations of cord colitis syndrome with GVHD
S. Shimoji, K. Kato, Y. Eriguchi, K. Takenaka, H. Iwasaki, T. Miyamoto, Y. Oda, K. Akashi, T. Teshima
BONE MARROW TRANSPLANTATION, 48, 9, 1249, 1252, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Efficacy and Safety of Aprepitant in Allogeneic Hematopoietic Stem Cell Transplantation
Mayako Uchida, Koji Kato, Hiroaki Ikesue, Kimiko Ichinose, Hiromi Hiraiwa, Asako Sakurai, Tsuyoshi Muta, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Takanori Teshima, Motoaki Shiratsuchi, Kimitaka Suetsugu, Kenichiro Nagata, Nobuaki Egashira, Koichi Akashi, Ryozo Oishi
PHARMACOTHERAPY, 33, 9, 893, 901, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study.
Kazuo Muroi, Koichi Miyamura, Kazuteru Ohashi, Makoto Murata, Tetsuya Eto, Naoki Kobayashi, Shuichi Taniguchi, Masahiro Imamura, Kiyoshi Ando, Shunichi Kato, Takehiko Mori, Takanori Teshima, Masaki Mori, Keiya Ozawa
International journal of hematology, 98, 2, 206, 13, 2013年08月, ［査読有り］, ［国内誌］
英語, We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients with hematological malignancies who suffered from grade II (9 patients) or III aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9 patients), and liver (3 patients). Seven patients had two involved organs. The median age was 52. No other second-line agents were given. MSCs were given at a dose of 2 × 10(6) cells/kg for each infusion twice a week for 4 weeks. If needed, patients were continuously given MSCs weekly for an additional 4 weeks. By week 4, 13 of 14 patients (92.9 %) had responded to MSC therapy with a complete response (CR; n = 8) or partial response (PR; n = 5). At 24 weeks, 11 patients (10 with CR and 1 with PR) were alive. At 96 weeks, 8 patients were alive in CR. A total of 6 patients died, attributable to the following: underlying disease relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1), ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects associated with MSC infusion were observed. Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD.

Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission
Tetsuya Eto, Ken Takase, Toshihiro Miyamoto, Yuju Ohno, Tomohiko Kamimura, Koji Nagafuji, Yasushi Takamatsu, Takanori Teshima, Hisashi Gondo, Shuichi Taniguchi, Koichi Akashi, Mine Harada
INTERNATIONAL JOURNAL OF HEMATOLOGY, 98, 2, 186, 196, 2013年08月, ［査読有り］
英語, 研究論文（学術雑誌）

A novel filtration method for cord blood processing using a polyester fabric filter
T. Shima, N. Forraz, N. Sato, T. Yamauchi, H. Iwasaki, K. Takenaka, K. Akashi, C. McGuckin, T. Teshima
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 35, 4, 436, 446, 2013年08月, ［査読有り］
英語, 研究論文（学術雑誌）

BMT Tandem meetingに参加して　　　　　　　　　　　　　　　
豊嶋 崇徳
血液フロンティア, 23, 6, 822, 824, 2013年06月
日本語, 研究論文（学術雑誌）

HIV感染者における梅毒血清反応と抗カルジオリピン抗体に関する検討
遠藤知之, 藤本勝也, 吉田美穂, 竹村龍, 杉田純一, 重松明男, 近藤健, 橋野聡, 田中淳司, 佐藤典宏, 豊嶋崇徳
日本エイズ学会誌, 15, 2, 113, 118, (一社)日本エイズ学会, 2013年05月, ［査読有り］
日本語

Effectiveness and Safety of Antiemetic Aprepitant in Japanese Patients Receiving High-Dose Chemotherapy Prior to Autologous Hematopoietic Stem Cell Transplantation
Mayako Uchida, Hiroaki Ikesue, Toshihiro Miyamoto, Koji Kato, Kimitaka Suetsugu, Kimiko Ichinose, Hiromi Hiraiwa, Asako Sakurai, Katsuto Takenaka, Tsuyoshi Muta, Hiromi Iwasaki, Takanori Teshima, Motoaki Shiratsuchi, Nobuaki Egashira, Koichi Akashi, Ryozo Oishia
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 36, 5, 819, 824, 2013年05月, ［査読有り］
英語, 研究論文（学術雑誌）

～なぜ、今GVHDなのか～　　　　　　　　　　　　　　　
豊嶋 崇徳
血液フロンティア, 23, 5, 17, 19, 2013年05月
日本語, 研究論文（学術雑誌）

Decrease in Venous Irritation by Adjusting the Concentration of Injected Bendamustine
Hiroyuki Watanabe, Hiroaki Ikesue, Tomoko Tsujikawa, Kenichiro Nagata, Mayako Uchida, Kimitaka Suetsugu, Nobuaki Egashira, Tsuyoshi Muta, Koji Kato, Katsuto Takenaka, Saiji Ohga, Takamitsu Matsushima, Motoaki Shiratsuchi, Toshihiro Miyamoto, Takanori Teshima, Koichi Akashi, Ryozo Oishi
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 36, 4, 574, 578, 2013年04月, ［査読有り］
英語, 研究論文（学術雑誌）

骨髄抑制時のエマージェンシー　　　　　　　　　　　　　　　
白鳥聡一, 豊嶋崇徳
成人病と生活習慣病, 43, 4, 533, 538, 2013年04月
日本語, 研究論文（学術雑誌）

Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma
Koji Kato, Toshihiro Miyamoto, Akihiko Numata, Takashi Nakaike, Hideyo Oka, Ayano Yurino, Takuro Kuriyama, Yasuo Mori, Satoshi Yamasaki, Tsuyoshi Muta, Katsuto Takenaka, Hiromi Iwasaki, Takanori Teshima, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 97, 3, 430, 432, 2013年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Diagnosis and evaluation of intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation following reduced-intensity and myeloablative conditioning regimens
Satoshi Yamasaki, Akiko Miyagi-Maeshima, Yasuo Kakugawa, Yoshihiro Matsuno, Fusako Ohara-Waki, Shigeo Fuji, Yuriko Morita-Hoshi, Masakazu Mori, Sung-Won Kim, Shin-ichiro Mori, Takahiro Fukuda, Ryuji Tanosaki, Tadakazu Shimoda, Kensei Tobinai, Daizo Saito, Yoichi Takaue, Takanori Teshima, Yuji Heike
INTERNATIONAL JOURNAL OF HEMATOLOGY, 97, 3, 421, 426, 2013年03月, ［査読有り］
英語, 研究論文（学術雑誌）

急性および慢性GVHDの診断とマネジメント　　　　　　　　　　　　　　　
豊嶋 崇徳
血液内科, 66, 3, 392, 398, 2013年03月
日本語, 研究論文（学術雑誌）

造血幹細胞移植の話題 ASH発表演題より
豊嶋 崇徳, 高見 昭良, 谷口 修一, 村田 誠
Therapeutic Research, 34, 3, 259, 266, ライフサイエンス出版(株), 2013年03月, ［査読有り］
日本語

Antiemetic effectiveness and safety of aprepitant in patients with hematologic malignancy receiving multiday chemotherapy
Mayako Uchida, Hiroaki Ikesue, Koji Kato, Kimiko Ichinose, Hiromi Hiraiwa, Asako Sakurai, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Takanori Teshima, Nobuaki Egashira, Koichi Akashi, Ryozo Oishi
American Journal of Health-System Pharmacy, 70, 4, 343, 349, 2013年02月15日, ［査読有り］
英語, 研究論文（学術雑誌）

GVHD予防の最前線
杉田純一, 豊嶋崇徳
臨床血液, 54, 2, 156, 166, The Japanese Society of Hematology, 2013年02月
日本語, 研究論文（学術雑誌）

Successful engraftment in hla-mismatched bone marrow transplantation despite the persistence of high-level donor-specific anti-HLA-DR antibody
Souichi Shiratori, Makoto Ito, Maki Yoneoka, Koji Hayasaka, Eiko Hayase, Junko Iwasaki, Junichi Sugita, Akio Shigematsu, Katsuya Fujimoto, Takeshi Kondo, Chikara Shimizu, Takanori Teshima
Transplantation, 96, 5, e34, e35, 2013年, ［査読有り］
英語

多発性骨髄腫患者の末梢血幹細胞採取に対するbortezomibを含む導入療法の影響
牟田毅, 宮本敏浩, 藤崎智明, 大野裕樹, 上村智彦, 平安山知子, 加藤光次, 竹中克斗, 岩崎浩巳, 衛藤徹也, 高松泰, 豊嶋崇徳, 赤司浩一
臨床血液, 54, 1, 109, 116, (一社)日本血液学会-東京事務局, 2013年01月, ［査読有り］
日本語

Quantitation of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic hematopoietic stem cell transplantation
Takahiro Shima, Toshihiro Miyamoto, Yoshikane Kikushige, Yasuo Mori, Kenjiro Kamezaki, Ken Takase, Hideho Henzan, Akihiko Numata, Yoshikiyo Ito, Katsuto Takenaka, Hiromi Iwasaki, Tomohiko Kamimura, Tetsuya Eto, Koji Nagafuji, Takanori Teshima, Koji Kato, Koichi Akashi
BLOOD, 121, 5, 840, 848, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Evaluation of the Feasibility and Efficacy of Autologous Stem Cell Transplantation in Elderly Patients with Multiple Myeloma
Tsuyoshi Muta, Toshihiro Miyamoto, Tomoaki Fujisaki, Yuju Ohno, Tomohiko Kamimura, Koji Kato, Katsuto Takenaka, Hiromi Iwasaki, Tetsuya Eto, Yasushi Takamatsu, Takanori Teshima, Koichi Akashi
INTERNAL MEDICINE, 52, 1, 63, 70, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）

安全な血液製剤の供給のために　　　　　　　　　　　　　　　
豊嶋 崇徳
血液製剤headline, 9, 3, 2013年
日本語, 研究論文（学術雑誌）

個別化医療―臨床試験におけるバイオーマーカーと標準療法の導入　　　　　　　　　　　　　　　
豊嶋 崇徳
Trends in Hematological Malignancies, 5, 2, 50, 53, 2013年
日本語, 研究論文（学術雑誌）

左副腎原発メトトレキサート関連悪性リンパ腫の一例
亀田啓, 中垣整, 永井聡, 近藤琢磨, 三橋智子, 松野吉宏, 安部崇重, 篠原信雄, 野々村克也, 白鳥聡一, 豊嶋崇徳, 三好秀明, 清水力, 清水力, 渥美達也
日本内分泌学会雑誌, 88, 3, 1034, 2012年12月20日
日本語

Engulfment of hematopoietic stem cells caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis
Takuro Kuriyama, Katsuto Takenaka, Kentaro Kohno, Takuji Yamauchi, Shinya Daitoku, Goichi Yoshimoto, Yoshikane Kikushige, Junji Kishimoto, Yasunobu Abe, Naoki Harada, Toshihiro Miyamoto, Hiromi Iwasaki, Takanori Teshima, Koichi Akashi
BLOOD, 120, 19, 4058, 4067, 2012年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Low incidence of adenovirus hemorrhagic cystitis following autologous hematopoietic stem cell transplantation in the rituximab era
Yasuo Mori, Toshihiro Miyamoto, Kenjiro Kamezaki, Koji Kato, Yoshikane Kikushige, Shuichiro Takashima, Shingo Urata, Shinji Shimoda, Nobuyuki Shimono, Katsuto Takenaka, Hiromi Iwasaki, Koji Nagafuji, Takanori Teshima, Koichi Akashi
AMERICAN JOURNAL OF HEMATOLOGY, 87, 8, 828, 830, 2012年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Validation of pretransplantation assessment of mortality risk score in the outcome of hematopoietic SCT in non-Caucasians
Y. Mori, T. Teshima, K. Kamezaki, K. Kato, K. Takenaka, H. Iwasaki, T. Miyamoto, K. Nagafuji, T. Eto, K. Akashi
BONE MARROW TRANSPLANTATION, 47, 8, 1075, 1081, 2012年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of -defensins.
Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, Shimoda S, Iwasaki H, Shimono N, Ayabe T, Akashi K, Teshima T
Blood, 120, 1, 223, 231, 2012年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Initial low-dose valganciclovir as a preemptive therapy is effective for cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients
Katsuto Takenaka, Koji Nagafuji, Ken Takase, Tomohiko Kamimura, Yasuo Mori, Yoshikiyo Ito, Yukiko Nishi, Hideho Henzan, Koji Kato, Naoki Harada, Tetsuya Eto, Toshihiro Miyamoto, Takanori Teshima, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 96, 1, 94, 100, 2012年07月, ［査読有り］
英語, 研究論文（学術雑誌）

GVHD-associated immunodeficiency: soil or seed?
Takanori Teshima
Blood, 119, 24, 5618, 5619, 2012年06月14日, ［査読有り］
研究論文（学術雑誌）

Successful treatment by donor lymphocyte infusion of adult T-cell leukemia/lymphoma relapse following allogeneic hematopoietic stem cell transplantation
Tomohiko Kamimura, Toshihiro Miyamoto, Noriaki Kawano, Akihiko Numata, Yoshikiyo Ito, Yong Chong, Koji Nagafuji, Takanori Teshima, Shin Hayashi, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 95, 6, 725, 730, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Different Risk Factors Related to Adenovirus- or BK Virus-Associated Hemorrhagic Cystitis following Allogeneic Stem Cell Transplantation
Yasuo Mori, Toshihiro Miyamoto, Koji Kato, Kenjiro Kamezaki, Takuro Kuriyama, Seido Oku, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Motoaki Shiratsuchi, Yasunobu Abe, Koji Nagafuji, Takanori Teshima, Koichi Akashi
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 18, 3, 458, 465, 2012年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Plasma biomarkers of lower gastrointestinal and liver acute GVHD
Andrew C. Harris, James L. M. Ferrara, Thomas M. Braun, Ernst Holler, Takanori Teshima, John E. Levine, Sung W. Choi, Karin Landfried, Koichi Akashi, Mark Vander Lugt, Daniel R. Couriel, Pavan Reddy, Sophie Paczesny
BLOOD, 119, 12, 2960, 2963, 2012年03月, ［査読有り］
英語, 研究論文（学術雑誌）

特発性血小板減少性紫斑病におけるセファランチン大量療法の有用性 -後方視的多施設共同研究-
高畑むつみ, 橋野聡, 藤本勝也, 遠藤知之, 小林直樹, 黒澤光俊, 岩崎博, 三宅高義, 幸田久平, 前川勲, 笹川裕, 堤豊, 宮城島拓人, 田中淳司, 今村雅寛, 豊嶋崇徳
臨床血液, 53, 12, 1983, 1990, (一社)日本血液学会-東京事務局, 2012年, ［査読有り］
日本語

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17
Hisakazu Nishimori, Yoshinobu Maeda, Takanori Teshima, Haruko Sugiyama, Koichiro Kobayashi, Yoshiko Yamasuji, Sachiyo Kadohisa, Hidetaka Uryu, Kengo Takeuchi, Takehiro Tanaka, Tadashi Yoshino, Yoichiro Iwakura, Mitsune Tanimoto
BLOOD, 119, 1, 285, 295, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）

GVHDのメカニズムとその克服に向けた細胞療法の展開　　　　　　　　　　　　　　　
豊嶋 崇徳
医学のあゆみ, 240, 5, 460, 464, 2012年
日本語, 研究論文（学術雑誌）

Wntシグナルを標的とした腸管GVHDの制御
豊嶋 崇徳
血液内科, 64, 2, 197, 201, 科学評論社, 2012年
日本語, 研究論文（学術雑誌）

移植片対宿主病(GVHD)のマネジメント　　　　　　　　　　　　　　　
豊嶋 崇徳
がん看護, 17, 3, 354, 356, 2012年
日本語, 研究論文（学術雑誌）

GVHDの成因と治療　　　　　　　　　　　　　　　
豊嶋 崇徳
日本臨床, 70, 2, 264, 268, 2012年
日本語, 研究論文（学術雑誌）

ミニ移植における移植片対宿主病(GVHD)と移植片対白血病(GVL)効果　　　　　　　　　　　　　　　
重松明男, 豊嶋崇徳
血液フロンティア, 22, 10, 23, 30, 2012年
日本語, 研究論文（学術雑誌）

献血者不足とPatient Blood Management　　　　　　　　　　　　　　　
平安山知子, 豊嶋崇徳
医学のあゆみ, 243, 4, 311, 315, 2012年
日本語, 研究論文（学術雑誌）

Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease
James L. M. Ferrara, Andrew C. Harris, Joel K. Greenson, Thomas M. Braun, Ernst Holler, Takanori Teshima, John E. Levine, Sung W. J. Choi, Elisabeth Huber, Karin Landfried, Koichi Akashi, Mark Vander Lugt, Pavan Reddy, Alice Chin, Qing Zhang, Samir Hanash, Sophie Paczesny
BLOOD, 118, 25, 6702, 6708, 2011年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Th1 and Th17 join forces for acute GVHD
Takanori Teshima
Blood, 118, 18, 4765, 4767, 2011年11月03日, ［査読有り］
研究論文（学術雑誌）

Blood-cell banking for workers at the Fukushima Daiichi nuclear power plant – Authors' reply
Tetsuya Tanimoto, Koichiro Yuji, Naoyuki Uchida, Miwako Hosoda, Yuko Kodama, Takanori Teshima, Shuichi Taniguchi
The Lancet, 378, 9790, 484, 485, Elsevier BV, 2011年08月
英語

Successful allogeneic stem cell transplantation in two patients with acute myelogenous leukaemia and invasive aspergillosis by antifungal combination therapy
Takatoshi Aoki, Toshihiro Miyamoto, Yasuo Mori, Goichi Yoshimoto, Takuji Yamauchi, Kenjiro Kamezaki, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Koji Nagafuji, Nobuyuki Shimono, Takanori Teshima, Koichi Akashi
MYCOSES, 54, 4, E255, E259, 2011年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Regulatory T cells and IL-17-producing cells in graft-versus-host disease
Takanori Teshima, Yoshinobu Maeda, Katsutoshi Ozaki
IMMUNOTHERAPY, 3, 7, 833, 852, 2011年07月
英語, 研究論文（学術雑誌）

Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission: Fukuoka BMT Group observations and a literature review
T. Kamimura, T. Miyamoto, K. Nagafuji, A. Numata, H. Henzan, K. Takase, Y. Ito, Y. Ohno, T. Fujisaki, T. Eto, Y. Takamatsu, T. Teshima, H. Gondo, K. Akashi, S. Taniguchi, M. Harada
BONE MARROW TRANSPLANTATION, 46, 6, 820, 826, 2011年06月, ［査読有り］
英語

Analysis of immune reconstitution after autologous CD34(+) stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4(+) T cells
Hiroshi Tsukamoto, Koji Nagafuji, Takahiko Horiuchi, Hiroki Mitoma, Hiroaki Niiro, Yojiro Arinobu, Yasushi Inoue, Kentaro To, Toshihiro Miyamoto, Hiromi Iwasaki, Takanori Teshima, Mine Harada, Koichi Akashi
RHEUMATOLOGY, 50, 5, 944, 952, 2011年05月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Safety of workers at the Fukushima Daiichi nuclear power plant
Tetsuya Tanimoto, Naoyuki Uchida, Yuko Kodama, Takanori Teshima, Shuichi Taniguchi
LANCET, 377, 9776, 1489, 1490, 2011年04月, ［査読有り］
英語

The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells
Shuichiro Takashima, Masanori Kadowaki, Kazutoshi Aoyama, Motoko Koyama, Takeshi Oshima, Kazuma Tomizuka, Koichi Akashi, Takanori Teshima
JOURNAL OF EXPERIMENTAL MEDICINE, 208, 2, 285, 294, 2011年02月, ［査読有り］
英語, 研究論文（学術雑誌）

血小板輸血後に不規則抗体が検出された２症例
吉居真由, 山口恭子, 池松陽子, 江頭貞臣, 豊嶋崇徳, 赤司浩一
日本輸血細胞治療学会誌, 57, 6, 465, 469, 2011年, ［査読有り］
[症例報告]

造血幹細胞移植の新たな感染対策
江里口芳裕, 前原依子, 下野信行, 宮本敏浩, 赤司浩一, 豊嶋崇徳
無菌生物, 41, 1, 45, 47, 日本無菌生物ノートバイオロジー学会, 2011年, ［査読有り］
日本語

Diagnostic Value of Serum Procalcitonin and C-reactive Protein for Infections after Allogeneic Hematopoietic Stem Cell Transplantation versus Nontransplant Setting
Yasuo Mori, Kohta Miyawaki, Koji Kato, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Toshihiro Miyamoto, Koichi Akashi, Takanori Teshima
INTERNAL MEDICINE, 50, 19, 2149, 2155, 2011年, ［査読有り］
英語, 研究論文（学術雑誌）

GVHDの制御　　　　　　　　　　　　　　　
豊嶋 崇徳
血液フロンティア, 21, 3, 443, 452, 2011年
日本語, 研究論文（学術雑誌）

移植片対宿主病とToll-like receptors
青山一利, 小山幹子, 豊嶋崇徳
臨床免疫・アレルギー科, 55, 5, 566, 571, 科学評論社, 2011年
日本語, 研究論文（学術雑誌）

造血幹細胞移植とウイルス感染症　　　　　　　　　　　　　　　
豊嶋 崇徳
臨床とウイルス, 39, 1, 51, 61, 2011年
日本語, 研究論文（学術雑誌）

Wnt作動薬R-spondin1は腸幹細胞を保護して全身性移植片対宿主病を軽減する　　　　　　　　　　　　　　　
高嶋秀一郎, 豊嶋崇徳
実験医学, 29, 13, 2139, 2142, 2011年
日本語, 研究論文（学術雑誌）

臓器・細胞移植と輸血の現状　　　　　　　　　　　　　　　
豊嶋 崇徳
血液事業, 33, 4, 439, 440, 2011年
日本語, 研究論文（学術雑誌）

造血幹細胞移植後の感染症 ―免疫力ゼロからの闘い―　　　　　　　　　　　　　　　
豊嶋 崇徳
医薬ジャーナル, 47, 11, 2790, 2794, 2011年
日本語, 研究論文（学術雑誌）

造血細胞移植後の免疫不全とその予防治療　　　　　　　　　　　　　　　
豊嶋 崇徳
日本医師会雑誌, 140, 7, 1418, 2011年
日本語, 研究論文（学術雑誌）

TIM-3 Is a Promising Target to Selectively Kill Acute Myeloid Leukemia Stem Cells
Yoshikane Kikushige, Takahiro Shima, Shin-ichiro Takayanagi, Shingo Urata, Toshihiro Miyamoto, Hiromi Iwasaki, Katsuto Takenaka, Takanori Teshima, Toshiyuki Tanaka, Yoshimasa Inagaki, Koichi Akashi
CELL STEM CELL, 7, 6, 708, 717, 2010年12月, ［査読有り］
英語, 研究論文（学術雑誌）

High Incidence of Human Herpes Virus 6-Associated Encephalitis/Myelitis following a Second Unrelated Cord Blood Transplantation
Yasuo Mori, Toshihiro Miyamoto, Koji Nagafuji, Kenjiro Kamezaki, Asataro Yamamoto, Noriyuki Saito, Koji Kato, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Yasunobu Abe, Takanori Teshima, Koichi Akashi
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 16, 11, 1596, 1602, 2010年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Altered Effector CD4(+) T Cell Function in IL-21R(-/-) CD4(+) T Cell-Mediated Graft-Versus-Host Disease
Iekuni Oh, Katsutoshi Ozaki, Akiko Meguro, Keiko Hatanaka, Masanori Kadowaki, Haruko Matsu, Raine Tatara, Kazuya Sato, Yoichiro Iwakura, Susumu Nakae, Katsuko Sudo, Takanori Teshima, Warren J. Leonard, Keiya Ozawa
JOURNAL OF IMMUNOLOGY, 185, 3, 1920, 1926, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Cord blood stem cell transplantation in a patient with disseminated mucormycosis and acute myelogenous leukemia
T. Aoki, K. Kamezaki, T. Miyamoto, K. Nagafuji, Y. Mori, T. Yamauchi, K. Takenaka, H. Iwasaki, N. Harada, N. Shimono, T. Teshima, K. Akashi
TRANSPLANT INFECTIOUS DISEASE, 12, 3, 277, 279, 2010年06月, ［査読有り］
英語

High incidence of false-positive Aspergillus galactomannan test in multiple myeloma
Yasuo Mori, Yoji Nagasaki, Kenjiro Kamezaki, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Toshihiro Miyamoto, Yasunobu Abe, Nobuyuki Shimono, Koichi Akashi, Takanori Teshima
AMERICAN JOURNAL OF HEMATOLOGY, 85, 6, 449, 451, 2010年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Peripheral blood stem cell versus bone marrow transplantation from HLA-identical sibling donors in patients with leukemia: a propensity score-based comparison from the Japan Society for Hematopoietic Stem Cell Transplantation registry
Koji Nagafuji, Keitaro Matsuo, Takanori Teshima, Shin-ichiro Mori, Hisashi Sakamaki, Michihiro Hidaka, Hiroyasu Ogawa, Yoshihisa Kodera, Yoshinobu Kanda, Atsuo Maruta, Takehiko Mori, Fumiaki Yoshiba, Tatsuo Ichinohe, Masanobu Kasai, Yoshifusa Takatsuka, Kohmei Kubo, Hiroshi Sao, Yoshiko Atsuta, Ritsuro Suzuki, Takashi Yoshida, Masahiro Tsuchida, Mine Harada
INTERNATIONAL JOURNAL OF HEMATOLOGY, 91, 5, 855, 864, 2010年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group
A. Numata, T. Miyamoto, Y. Ohno, T. Kamimura, K. Kamezaki, T. Tanimoto, K. Takase, H. Henzan, K. Kato, K. Takenaka, T. Fukuda, N. Harada, K. Nagafuji, T. Teshima, K. Akashi, M. Harada, T. Eto
BONE MARROW TRANSPLANTATION, 45, 2, 311, 316, 2010年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Pulmonary Nocardiosis Developed in a Hematopoietic Stem Cell Transplant Recipient with Bronchiolitis Obliterans
Ruriko Nishida, Yasuo Mori, Hiromi Iwasaki, Takahito Tokuyama, Kenjiro Kamezaki, Yoji Nagasaki, Hideyo Oka, Kohta Miyawaki, Noriyuki Saito, Katsuto Takenaka, Naoki Harada, Toshihiro Miyamoto, Takanori Teshima, Koichi Akashi
INTERNAL MEDICINE, 49, 14, 1441, 1444, 2010年, ［査読有り］
英語, 研究論文（学術雑誌）

Successful treatment of refractory advanced nasal NK/T cell lymphoma with unrelated cord blood stem cell transplantation incorporating focal irradiation
Yasuo Mori, Takatoshi Aoki, Katsuto Takenaka, Takuji Yamauchi, Asataro Yamamoto, Kenjiro Kamezaki, Hiromi Iwasaki, Naoki Harada, Toshihiro Miyamoto, Koji Nagafuji, Takanori Teshima, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 91, 1, 107, 111, 2010年01月, ［査読有り］
英語, 研究論文（学術雑誌）

日本輸血・細胞治療学会による「輸血業務に関する総合的アンケート調査」における細胞治療に用いる細胞の採取、処理、保管に関する2008年の現状
池田和真, 長村登紀子, 田野崎隆二, 井関徹, 田中朝志, 豊嶋崇徳, 室井一男, 甲斐俊朗, 加藤俊一, 前川平, 佐川公矯, 高橋孝喜, 大戸斉
日本輸血細胞治療学会誌, 56, 5, 639, 644, The Japan Society of Transfusion Medicine and Cell Therapy, 2010年, ［査読有り］
日本語, 2008年実績に対する「輸血に関する総合的アンケート調査」の細胞治療に関する回答結果を報告する．調査は全国の7,857施設を対象とし，3,208（40.8％）から回答があった．輸血部門に専任の看護師がいる施設は53で，細胞の採取を行っている施設数は，自家末梢血幹細胞；108，同種末梢血幹細胞；75，非血縁骨髄；28，血縁骨髄；26，ドナーリンパ球；24，顆粒球；10であった．自家末梢血幹細胞については，48施設で採取が輸血部門で行われ，70施設が手順書を使用し，54施設が作業工程を記録し，59施設が規定のラベルを添付し，52施設が血液製剤に準じた照合を行い，70施設が自施設でフローサイトメトリー解析を行い，63施設が開放系処理に専用クリーン・ベンチを用いていた．処理後と解凍後の無菌検査を行っていると回答したのは7施設と1施設のみであった．成分採血の血管穿刺は82施設で担当診療科医師，成分採血装置のオペレーターは35施設で検査技師，31施設で臨床工学士，細胞の処理，凍結，保管，払出は大半の施設で検査技師により行われていた．検査技師が大きな役割を果たしていること，工程管理と品質管理には課題があることが明らかになった．

造血細胞移植ガイドライン 同種末梢血幹細胞移植のための健常人ドナーからの末梢血幹細胞動員・採取に関するガイドライン
豊嶋崇徳, 日野雅之, 田中淳司, 田野崎隆二, 長藤宏司, 宮村耕一, 小寺良尚, 日本造血細胞移植学会ガイドライン委員会, 日本輸血, 細胞治療学会アフェレーシス安全委員会
造血細胞移植モノグラフ vol.21，日本造血細胞移植学会, 2010年, ［査読有り］

リンパ腫・骨髄腫などにおける造血細胞移植の現状と展望　　　　　　　　　　　　　　　
豊嶋崇徳, 角南一貴, 前田嘉信, 名和由一郎, 平松靖
血液フロンティア, 20, 2, 234, 244, 2010年
日本語, 研究論文（学術雑誌）

造血細胞移植における母子間免疫寛容効果
青山一利, 松岡賢市, 豊嶋崇徳
血液・腫瘍科, 60, 4, 465, 470, 科学評論社, 2010年
日本語, 研究論文（学術雑誌）

骨髄増殖性腫瘍における血小板アフェレーシス　　　　　　　　　　　　　　　
平安山知子, 岩崎浩巳, 豊嶋崇徳, 赤司浩一
日本アフェレーシス学会雑誌, 29, 3, 287, 289, 2010年
日本語, 研究論文（学術雑誌）

造血幹細胞移植における慢性GVHDの発症機序　　　　　　　　　　　　　　　
門脇賢典, 豊嶋崇徳
臨床免疫・アレルギー科, 53, 3, 337, 342, 2010年
日本語, 研究論文（学術雑誌）

Breast milk and transplantation tolerance
Kazutoshi Aoyama, Ken-Ichi Matsuoka, Takanori Teshima
Chimerism, 1, 1, 19, 20, Taylor and Francis Inc., 2010年
英語, 研究論文（学術雑誌）

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation as Immunotherapy for Pancreatic Cancer
Yasunobu Abe, Tetsuhide Ito, Eishi Baba, Koji Nagafuji, Ken Kawabe, Ilseung Choi, Yoshiyuki Arita, Toshihiro Miyamoto, Takanori Teshima, Shuji Nakano, Mine Harada
PANCREAS, 38, 7, 815, 819, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Second unrelated cord blood transplantation using a reduced-intensity conditioning regimen combined with gemtuzumab ozogamicin in patients with relapsed acute myelogenous leukemia
Takuji Yamauchi, Yasuo Mori, Toshihiro Miyamoto, Kenjiro Kamezaki, Takatoshi Aoki, Asataro Yamamoto, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Koji Nagafuji, Takanori Teshima, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 90, 3, 416, 420, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease
Takanori Teshima, Koji Nagafuji, Hideho Henzan, Koichi Miyamura, Ken Takase, Michihiro Hidaka, Toshihiro Miyamoto, Katsuto Takenaka, Koichi Akashi, Mine Harada
INTERNATIONAL JOURNAL OF HEMATOLOGY, 90, 2, 253, 260, 2009年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Infectious complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases
K. Kohno, K. Nagafuji, H. Tsukamoto, T. Horiuchi, K. Takase, K. Aoki, H. Henzan, K. Kamezaki, K. Takenaka, T. Miyamoto, T. Teshima, M. Harada, K. Akashi
TRANSPLANT INFECTIOUS DISEASE, 11, 4, 318, 323, 2009年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Oral valganciclovir as preemptive therapy is effective for cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients
Katsuto Takenaka, Tetsuya Eto, Koji Nagafuji, Kenjiro Kamezaki, Yayoi Matsuo, Goichi Yoshimoto, Naoki Harada, Maki Yoshida, Hideho Henzan, Ken Takase, Toshihiro Miyamoto, Koichi Akashi, Mine Harada, Takanori Teshima
INTERNATIONAL JOURNAL OF HEMATOLOGY, 89, 2, 231, 237, 2009年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Disseminated tuberculosis following second unrelated cord blood transplantation for acute myelogenous leukemia
T. Shima, G. Yoshimoto, T. Miyamoto, S. Yoshida, K. Kamezaki, K. Takenaka, H. Iwasaki, N. Harada, K. Nagafuji, T. Teshima, N. Shimono, K. Akashi
TRANSPLANT INFECTIOUS DISEASE, 11, 1, 75, 77, 2009年02月, ［査読有り］
英語, 研究論文（学術雑誌）

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

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

Encephalomyelitis Mimicking Multiple Sclerosis Associated with Chronic Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation
Yayoi Matsuo, Kenjiro Kamezaki, Shoichiro Takeishi, Katsuto Takenaka, Tetsuya Eto, Atsushi Nonami, Toshihiro Miyamoto, Hiromi Iwasaki, Naoki Harada, Koji Nagafuji, Takanori Teshima, Koichi Akashi
INTERNAL MEDICINE, 48, 16, 1453, 1456, 2009年, ［査読有り］
英語, 研究論文（学術雑誌）

造血細胞移植ガイドライン インフルエンザ
豊嶋崇徳, 下野信行, 井上雅美, 日本造血細胞移植学会ガイドライン委員会
造血細胞移植モノグラフvol. 20，日本造血細胞移植学会．名古屋, 2009年, ［査読有り］

The engraftment of transplanted bone marrow-derived cells into the inner ear
Yorihisa Orita, Hidetsugu Tsujigiwa, Kazunori Nishizaki, Takanori Teshima, Junko Yoshinobu, Saeko Orita, Ayako Takeuchi, Yasushi Takeda, Hitoshi Nagatsuka, Noriyuki Nagai
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, 266, 1, 59, 63, 2009年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Allogeneic cell therapy from immunized donors with tumor antigen peptide enhances the antitumor effect after cyclophosphamide-using non-myeloablative allogeneic hematopoietic cell transplantation
Masumitsu Hamaguchi, Masatoshi Eto, Yoriyuki Kamiryo, Ario Takeuchi, Masahiko Harano, Katsunori Tatsugami, Takanori Teshima, Mamoru Harada, Yasunobu Yoshikai, Seiji Naito
CANCER SCIENCE, 100, 1, 138, 143, 2009年01月, ［査読有り］
英語, 研究論文（学術雑誌）

急性および慢性GVHDの病態と診断　　　　　　　　　　　　　　　
豊嶋 崇徳
内科, 104, 2, 206, 212, 2009年
日本語, 研究論文（学術雑誌）

同種造血幹細胞移植後のウイルス感染症　　　　　　　　　　　　　　　
豊嶋 崇徳
血液フロンティア, 19, 8, 1264, 1271, 2009年
日本語, 研究論文（学術雑誌）

慢性GVHDのマウスモデル　　　　　　　　　　　　　　　
豊嶋 崇徳
分子細胞治療, 8, 4, 55, 59, 2009年
日本語, 研究論文（学術雑誌）

GVHDにおける樹状細胞の役割　　　　　　　　　　　　　　　
豊嶋 崇徳
血液・腫瘍科, 59, 2, 233, 240, 2009年
日本語, 研究論文（学術雑誌）

造血細胞移植医療の基礎的・臨床的な新たな展開
豊嶋 崇徳
臨床血液, 50, 8, 617, 621, 「臨床血液」編集部, 2009年
日本語, 研究論文（学術雑誌）

同種造血幹細胞移植後の免疫再構築 造血細胞移植後の予防接種ガイドライン
東英一, 池亀和博, 恵美宣彦, 岡村純, 加藤剛二, 坂巻壽, 豊嶋崇徳, 星順隆, 室井一男, 森慎一郎, 矢野邦夫, 矢部普正
臨床血液, 50, 8, 642, 651, 「臨床血液」編集部, 2009年
日本語, 研究論文（学術雑誌）

GVHDとGVL
豊嶋 崇徳
臨床血液, 50, 10, 1407, 1419, 「臨床血液」編集部, 2009年
日本語, 研究論文（学術雑誌）

Additional acquisition of t(1;21)(p32;q22) in a patient relapsing with acute myelogenous leukemia with NUP98-HOXA9
Takatoshi Aoki, Toshihiro Miyamoto, Shuro Yoshida, Asataro Yamamoto, Takuji Yamauchi, Goichi Yoshimoto, Yasuo Mori, Kenjiro Kamezaki, Hiromi Iwasaki, Katsuto Takenaka, Naoki Harada, Koji Nagafuji, Takanori Teshima, Koichi Akashi
INTERNATIONAL JOURNAL OF HEMATOLOGY, 88, 5, 571, 574, 2008年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Successful treatment of parainfluenza virus 3 pneumonia with oral ribavirin and methylprednisolone in a bone marrow transplant recipient
Takahiro Shima, Goichi Yoshimoto, Atsushi Nonami, Shuro Yoshida, Kenjiro Kamezaki, Hiromi Iwasaki, Katsuto Takenaka, Toshihiro Miyamoto, Naoki Harada, Takanori Teshima, Koichi Akashi, Koji Nagafuji
INTERNATIONAL JOURNAL OF HEMATOLOGY, 88, 3, 336, 340, 2008年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Reduced-intensity unrelated donor bone marrow transplantation for hematologic malignancies
Sung-Won Kim, Keitaro Matsuo, Takahiro Fukuda, Masamichi Hara, Kosei Matsue, Shuichi Taniguchi, Tetsuya Eto, Mitsune Tanimoto, Atsushi Wake, Kazuo Hatanaka, Shinji Nakao, Yoji Ishida, Mine Harada, Atae Utsunomiya, Masahiro Imamura, Yoshinobu Kanda, Kazutaka Sunami, Fumio Kawano, Yoichi Takaue, Takanori Teshima
INTERNATIONAL JOURNAL OF HEMATOLOGY, 88, 3, 324, 330, 2008年10月, ［査読有り］
英語, 研究論文（学術雑誌）

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

再発・治療抵抗性多発性骨髄腫に対するbortezomib治療　　　　　　　　　　　　　　　
角南 一貴, 賀川 久美子, 尾崎 修治, 吾郷 浩厚, 平松 靖史, 豊嶋 崇徳, 赤司 浩一, 矢野 朋文, 朝倉 昇司, 下野 玄英, 名和 由一郎, 前田 嘉信, 多林 孝之, 牧田 雅典, 竹内 誠, 原 雅道, 宮田 明, 安倍 正博, 谷本 光音
臨床血液, 49, 9, 905, 905, (一社)日本血液学会-東京事務局, 2008年09月
日本語

Infectious complications in chronic graft-versus-host disease: a retrospective study of 145 recipients of allogeneic hematopoietic stem cell transplantation with reduced- and conventional-intensity conditioning regimens
S. Yamasaki, Y. Heike, S. Mori, T. Fukuda, D. Maruyama, R. Kato, E. Usui, K. Koido, S. Kim, R. Tanosaki, K. Tobinai, T. Teshima, Y. Takaue
TRANSPLANT INFECTIOUS DISEASE, 10, 4, 252, 259, 2008年08月, ［査読有り］
英語, 研究論文（学術雑誌）

An unexpected cause of a febrile patient with huge splenomegaly
Atsushi Nonami, Hidetaka Yamamoto, Masafumi Nakamura, Koji Nagafuji, Takanori Teshima
CLINICAL RHEUMATOLOGY, 27, 7, 941, 943, 2008年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Posttransplant administration of cyclophosphamide and donor lymphocyte infusion induces potent antitumor immunity to solid tumor
Masatoshi Eto, Yoriyuki Kamiryo, Ario Takeuchi, Masahiko Harano, Katsunori Tatsugami, Mamoru Harada, Keijiro Kiyoshima, Masumitsu Hamaguchi, Takanori Teshima, Masazumi Tsuneyoshi, Yasunobu Yoshikai, Seiji Naito
CLINICAL CANCER RESEARCH, 14, 9, 2833, 2840, 2008年05月, ［査読有り］
英語, 研究論文（学術雑誌）

造血細胞移植ガイドライン GVHD
豊嶋崇徳, 伊藤雅文, 井上雅美, 加藤剛二, 谷口修一, 宮村耕一, 森下剛久, 矢部普正, 日本造血細胞移植学会ガイドライン委員会
造血細胞移植モノグラフ，日本造血細胞移植学会．名古屋, 2008年, ［査読有り］

Preparation of functionally preserved CD4+CD25high regulatory T cells from leukapheresis products from ulcerative colitis patients, applicable to regulatory T-cell transfer therapy
Y. Sumida, K. Nakamura, K. Kanayama, H. Akiho, T. Teshima, R. Takayanagi
CYTOTHERAPY, 10, 7, 698, 710, 2008年, ［査読有り］
英語, 研究論文（学術雑誌）

GVHD制御と移植免疫寛容誘導の展望　　　　　　　　　　　　　　　
豊嶋 崇徳
日本組織適合性学会誌, 15, 1, 9, 26, 2008年
日本語, 研究論文（学術雑誌）

Chronic graft-versus-host disease: How can we release Prometheus?
Takanori Teshima, Thomas A. Wynn, Robert J. Soiffer, Ken-Ichi Matsuoka, Paul J. Martin
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 14, 1, 142, +, 2008年01月
英語, 研究論文（学術雑誌）

GVHDとGVLのメカニズムの再考察
豊嶋 崇徳
臨床血液, 49, 8, 592, 597, 「臨床血液」編集部, 2008年
日本語, 研究論文（学術雑誌）

母子間免疫寛容理論に基づく同種造血幹細胞移植
松岡 賢市, 青山 一利, 小山 幹子, 橋本 大吾, 朝倉 昇司, 一戸 辰夫, 谷本 光音, 豊嶋崇徳
岡山医学会雑誌, 120, 1, 23, 28, 岡山医学会, 2008年
日本語, 研究論文（学術雑誌）

A novel strategy for the treatment of acute graft-versus-host disease: removal of excessive inflammatory cytokines using the adsorbent
Takami A, Teshima T, Ushizaki K, Taniguchi T, Endo T, Sakurai H, Nakao S
BONE MARROW TRANSPLANTATION, 41, 1, S229, 2008年, ［査読有り］
34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group, Florence, ITALY, MAR 30-APR 02, 2008

Successful treatment of primary plasma cell leukaemia by allogeneic stem cell transplantation from haploidentical sibling
Atsushi Nonami, Toshihiro Miyamoto, Mika Kuroiwa, Yuya Kunisaki, Kenjiro Kamezaki, Katsuto Takenaka, Naoki Harada, Takanori Teshima, Mine Harada, Koji Nagafuji
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 37, 12, 969, 972, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）

A Novel Strategy for the Treatment of Acute Graft-Versus-Host Disease Using the Adsorbent To Remove Excessive Inflammatory Cytokines.
Akiyoshi Takami, Takanori Teshima, Koshin Ushizaki, Takumi Taniguchi, Tohru Endo, Hiroshi Sakurai, Yukio Kondo, Hirohito Yamazaki, Shigeru Shimadoi, Hirokazu Okumura, Shinji Nakao
Blood, 110, 11, 5001, 5001, 2007年11月16日
英語, 研究論文（学術雑誌）

Breast-Feeding Mediates Feto-Maternal Tolerance and Improves Outcome of Allogeneic Bone Marrow Transplantation.
Kazutoshi Aoyama, Ken-ichi Matsuoka, Daigo Hashimoto, Tatsuo Ichinohe, Mine Harada, Mitsune Tanimoto, Takanori Teshima
Blood, 110, 11, 2165, 2165, American Society of Hematology, 2007年11月16日
研究論文（学術雑誌）,
The widespread application of hematopoietic stem cell transplantation (HSCT) is limited by lack of a histocompatible donor in a proportion of patients who have a rare HLA haplotype. For these patients, allogeneic HSCT from an HLA-mismatched relative donor is complicated with a high incidence of severe graft-versus-host disease (GVHD). Exposure to noninherited maternal antigens (NIMAs) during pregnancy may have an impact on transplantation later in life. We recently demonstrated in a mouse model that a “child-to-mother” BMT from a NIMA-exposed donor reduced the mortality and morbidity of GVHD, but a “mother-to-child” BMT did not reduce GVHD (Matsuoka, 2006). We therefore hypothesized that breast-feeding could play a role on the induction of the tolerogenic NIMA effect. To test this hypothesis, we generated NIMA-exposed mice by mating a B6 (H–2b) male and a B6D2F1 (H–2b/d) female to generate H–2b/b offspring. These H–2b/b offspring were then nursed by either a B6D2F1 mother (in utero and oral exposure to NIMAs) or a B6 foster mother (in utero exposure to NIMAs). Transplantation from donors exposed to NIMA in utero alone produced more severe GVHD than BMT from in utero and orally exposed donors, demonstrating that breast-feeding is required for the induction of maximum NIMA effects. Next, to examine whether breast-feeding alone could mediate NIMA effects, we generated mice exposed to NIMA orally by nursing a new born B6 mouse with a B6D2F1 foster mother. CD4+ T cells isolated from these mice were cultured with B6D2F1 stimulators. Proliferation of these cells in response to NIMAs was significantly reduced in comparison to that from the controls. Lethally irradiated B6D2F1 recipients were transplanted with 2 × 106 T cells from these mice or controls together with 5 × 106 T cell-depleted bone marrow from control donors. Five days after transplant, donor T cell expansion and production of IFN-γ were significantly reduced in recipients of orally NIMA exposed donors than controls, resulting in a significant reduction of GVHD mortality (48% vs 80%, p&lt;0.05). The tolerogenic milk effects were completely abolished when lethally irradiated B6D2F1 mice were transplanted with 1 × 106 CD25-depleted CD4+ T cells from the milk-mediated NIMA-exposed mice, thus suggesting that donor CD4+ CD25+ T cells play a role in the tolerogenic milk effects. Next, we hypothesized that generation of regulatory T cells in neonates during lactation period is essential for the induction of the tolerogenic milk effects. The anti-CD25 mAbs, PC61, is capable of depleting CD25+ cells in vivo. New born B6 mice nursed by a B6D2F1 foster mother were subcutaneously injected with anti-CD25 mAbs on days 1 and 8 of life, resulting in a decrease in numbers of Foxp3+ CD4+ CD25+ cells in spleens at 3-week-old. These mice were used as BMT donors at 8-week-old when the numbers of the regulatory T cells had recovered. After BMT from these donors, reduction of GVHD was not observed. These results suggest that development of Foxp3+ CD4+ CD25+ regulatory T cells during lactation is critical for the induction of the tolerogenic milk effects. Our findings may have immediate implications for clinical BMT to use a NIMA-mismatched donor in the absence of a HLA-identical donor in HLA mismatched HSCT.

Toxoplasmosis encephalitis following severe graft-vs.-host disease after allogeneic hematopoietic stem cell transplantation: 17 yr experience in Fukuoka BMT group
Yayoi Matsuo, Shoichiro Takeishi, Toshihiro Miyamoto, Atsushi Nonami, Yoshikane Kikushige, Yuya Kunisaki, Kenjiro Kamezaki, Liping Tu, Hajime Hisaeda, Katsuto Takenaka, Naoki Harada, Tomohiko Kamimura, Yuju Ohno, Tetsuya Eto, Takanori Teshima, Hisashi Gondo, Mine Harada, Koji Nagafuji
EUROPEAN JOURNAL OF HAEMATOLOGY, 79, 4, 317, 321, 2007年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation
Yasuo Mori, Goichi Yoshimoto, Takashi Kumano, Toshihiro Miyamoto, Tadafumi Lino, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Naoko Kinukawa, Koji Nagafuji, Takanori Teshima, Kazuya Shimoda, Koichi Akashi, Mine Harada
EUROPEAN JOURNAL OF HAEMATOLOGY, 79, 1, 17, 24, 2007年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Successful treatment of primary cardiac lymphoma by rituximab-CHOP and high-dose chemotherapy with autologous peripheral blood stem cell transplantation
Atsushi Nonami, Katsuto Takenaka, Kenjiro Kamezaki, Toshihiro Miyamoto, Naoki Harada, Koji Nagafuji, Takanori Teshima, Mine Harada
INTERNATIONAL JOURNAL OF HEMATOLOGY, 85, 3, 264, 266, 2007年04月, ［査読有り］
英語, 研究論文（学術雑誌）

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

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

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

Successful treatment of myelodysplastic syndrome (MDS)-related intestinal Behçet's disease by up-front cord blood transplantation
Nonami A, Takenaka K, Sumida C, Aizawa K, Kamezaki K, Miyamoto T, Harada N, Nagafuji K, Teshima T, Harada M
Intern Med, 46, 20, 1753, 1756, 2007年, ［査読有り］
英語, 研究論文（学術雑誌）

Collection of mobilized peripheral blood stem cells from a donor with severe iron deficient anemia
Kenjirou Kamezaki, Toshihiro Miyamoto, Tomoko Henzan, Akihiko Numata, Hiromi Iwasaki, Koji Nagafuji, Mine Harada, Takanori Teshima, Koichi Akashi
JOURNAL OF CLINICAL APHERESIS, 22, 5, 292, 294, 2007年, ［査読有り］
英語, 研究論文（学術雑誌）

輸血前後の感染症マーカー検査についての日本輸血・細胞治療学会運用マニュアル
熊川みどり, 長井一浩, 豊嶋崇徳, 水落利明, 佐川公矯, 高橋孝喜, 山口一成
日本輸血細胞治療学会誌, 53, 6, 602, 606, 2007年, ［査読有り］
日本語

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

GVHDとGVLの基礎と臨床応用　　　　　　　　　　　　　　　
豊嶋 崇徳
血液フロンティア, 17, 3, 357, 366, 2007年
日本語, 研究論文（学術雑誌）

GVHDとGVL　　　　　　　　　　　　　　　
豊嶋 崇徳
分子細胞治療, 6, 2, 118, 123, 2007年
日本語, 研究論文（学術雑誌）

はじめに．造血幹細胞移植後のGVHD　　　　　　　　　　　　　　　
豊嶋 崇徳
医学のあゆみ, 222, 3, 157, 2007年
日本語, 研究論文（学術雑誌）

急性GVHDの病態と治療　　　　　　　　　　　　　　　
豊嶋 崇徳
医学のあゆみ, 222, 3, 165, 169, 2007年
日本語, 研究論文（学術雑誌）

ドナー由来胸腺依存性Ｔ細胞によるGVHD
佐古田幸美, 豊嶋崇徳
血液・腫瘍科, 55, 4, 458, 463, 科学評論社, 2007年
日本語, 研究論文（学術雑誌）

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

Bone marrow transplantation improves outcome in a mouse model of congenital muscular dystrophy
Hiroki Hagiwara, Yutaka Ohsawa, Shoji Asakura, Tatsufumi Murakami, Takanori Teshima, Yoshihide Sunada
FEBS LETTERS, 580, 18, 4463, 4468, 2006年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Calcineurin inhibitor-induced irreversible neuropathic pain after allogeneic hematopoietic stem cell transplantation
N Fujii, K Ikeda, M Koyama, K Aoyama, T Masunari, E Kondo, T Matsuzaki, S Mizobuchi, A Hiraki, T Teshima, K Shinagawa, F Ishimaru, M Tanimoto
INTERNATIONAL JOURNAL OF HEMATOLOGY, 83, 5, 459, 461, 2006年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Impact of fetal-maternal tolerance in hematopoietic stem cell transplantation
Takanori Teshima, Ken-ichi Matsuoka, Tatsuo Ichinohe
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS, 54, 3, 165, 172, 2006年05月
英語, 研究論文（学術雑誌）

Complete donor chimaerism of Langerhans cells in lymph node early after allogeneic bone marrow transplantation
K Ikeda, T Shichishima, T Teshima, K Ogawa, A Nakamura-Shichishima, H Tajima, H Noji, Y Hashimoto, K Takeyama, T Ishibashi, H Ohto, M Abe, Y Maruyama
EUROPEAN JOURNAL OF HAEMATOLOGY, 76, 3, 261, 264, 2006年03月, ［査読有り］
英語, 研究論文（学術雑誌）

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

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

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

GVHDとGVLの病態生理　　　　　　　　　　　　　　　
豊嶋 崇徳
血液・腫瘍科, 52, 3, 344, 359, 2006年
日本語, 研究論文（学術雑誌）

サイトカインとGVHD　　　　　　　　　　　　　　　
豊嶋 崇徳
内科, 98, 2, 313, 318, 2006年
日本語, 研究論文（学術雑誌）

Maternal antigensへの免疫学的寛容とCD4+CD25+制御性T細胞　　　　　　　　　　　　　　　
松岡賢市, 一戸辰夫, 豊嶋崇徳
血液・腫瘍科, 53, 4, 362, 367, 2006年
日本語, 研究論文（学術雑誌）

造血幹細胞移植における免疫反応―移植片対宿主病―　　　　　　　　　　　　　　　
豊嶋 崇徳
Sysmex Journal, 29, 39, 48, 2006年
日本語, 研究論文（学術雑誌）

同種免疫反応の制御 Graft-versus-host disease (GVHD)　　　　　　　　　　　　　　　
豊嶋 崇徳
今日の移植, 19, 1, 65, 72, 2006年
日本語, 研究論文（学術雑誌）

Fetal-maternal microchimerism: impact on hematopoietic stem cell transplantation
T Ichinohe, T Teshima, K Matsuoka, E Maruya, H Saji
CURRENT OPINION IN IMMUNOLOGY, 17, 5, 546, 552, 2005年10月
英語, 研究論文（学術雑誌）

Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors
T Teshima, K Matsuo, K Matsue, F Kawano, S Taniguchi, M Hara, K Hatanaka, M Tanimoto, M Harada, S Nakao, Y Abe, A Wake, T Eto, Y Takemoto, M Imamura, S Takahashi, Y Ishida, Y Kanda, M Kasai, Y Takaue
BRITISH JOURNAL OF HAEMATOLOGY, 130, 4, 575, 587, 2005年08月, ［査読有り］
英語, 研究論文（学術雑誌）

The engraftment of transplanted bone marrow-derived cells into the olfactory epithelium
H Tsujigiwa, K Nishizaki, T Teshima, Y Takeda, J Yoshinobu, A Takeuchi, Y Orita, Y Sugata, H Nagatsuka, N Nagai
BRAIN RESEARCH, 1052, 1, 10, 15, 2005年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Early immune reaction after reduced-intensity cord-blood transplantation for adult patients
Y Kishi, M Kami, S Miyakoshi, Y Kanda, N Murashige, T Teshima, E Kusumi, S Hara, T Matsumura, K Yuji, K Masuoka, A Wake, S Morinaga, M Kanemaru, T Hayashi, Y Tanaka, S Taniguchi
TRANSPLANTATION, 80, 1, 34, 40, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Both perforin and Fas ligand are required for the regulation of alloreactive CD8(+) T cells during acute graft-versus-host disease
Y Maeda, RB Levy, P Reddy, C Liu, SG Clouthier, T Teshima, JLM Ferrara
BLOOD, 105, 5, 2023, 2027, 2005年03月, ［査読有り］
英語, 研究論文（学術雑誌）

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

Graft-versus-host disease (GVHD)の制御
豊嶋 崇徳
日本内科学会誌, 94, 7, 1356, 1361, The Japanese Society of Internal Medicine, 2005年
日本語, 研究論文（学術雑誌）, Cyclosprineの導入によって急性GVHDの制御がある程度達成され,同種造血幹細胞移植は急速に普及した.しかし一旦発症した急性GVHDの治療成績はいまだ不十分で,さらに慢性GVHDの減少は依然達成されておらず,移植後のQOL (quality of life)と生命予後の大きな危険因子となっている.近年,新規薬剤や各種抗体療法の開発,研究が進み,新たな細胞療法の展開とあわせて注目される.

GVHDの発症メカニズム
豊嶋 崇徳
日本小児血液学会雑誌, 19, 84, 86, 2005年
日本語, 研究論文（学術雑誌）

GVHDとGVTの病態　　　　　　　　　　　　　　　
豊嶋 崇徳
綜合臨床, 54, 6, 1737, 1743, 2005年
日本語, 研究論文（学術雑誌）

移植免疫と腫瘍免疫　　　　　　　　　　　　　　　
豊嶋 崇徳
Urology View, 3, 3, 48, 52, 2005年
日本語, 研究論文（学術雑誌）

NKT細胞刺激による急性GVHD予防　　　　　　　　　　　　　　　
橋本 大吾, 朝倉 昇司, 三宅 幸子, 山村 隆, Van Kaer Luc, Liu Chen, 谷本 光音, 豊嶋 崇徳
日本血液学会・日本臨床血液学会総会プログラム・抄録集, 66回・46回, 747, 747, 日本臨床血液学会, 2004年09月
日本語

Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease
UA Duffner, Y Maeda, KR Cooke, P Reddy, R Ordemann, C Liu, JLM Ferrara, T Teshima
JOURNAL OF IMMUNOLOGY, 172, 12, 7393, 7398, 2004年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Peripheral blood circulating immature cell counts predict CD34+ cell yields in G-CSF-induced PBPC mobilization in healthy donors
T Kozuka, K Ikeda, T Teshima, C Yoshida, K Shinagawa, K Kojima, K Matsuo, A Bessho, K Sunami, Y Hiramatsu, Y Maeda, T Noguchi, K Yamamoto, N Fujii, T Imai, KK Kusumoto, K Masuda, K Takenaka, F Ishimaru, K Niiya, N Koide, M Tanimoto, M Harada
TRANSFUSION, 44, 4, 526, 532, 2004年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells
M Niiya, K Niiya, M Shibakura, N Asaumi, C Yoshida, K Shinagawa, T Teshima, F Ishimaru, K Ikeda, M Tanimoto
ONCOLOGY, 67, 3-4, 310, 319, 2004年, ［査読有り］
英語, 研究論文（学術雑誌）

[Clinical evaluation of cefozopran as treatment for febrile neutropenia].
Takashi Saito, Masamichi Hara, Katsuji Shinagawa, Yuichiro Nawa, Koichi Nakase, Makoto Takeuchi, Akira Miyata, Shunnichi Fukuda, Kazutaka Sunami, Kenji Imajoh, Tomofumi Yano, Kensuke Kojima, Takanori Teshima, Nobuharu Fujii, Fumihiko Ishimaru, Kazuma Ikeda, Mine Harada, Mitsune Tanimoto
Gan to kagaku ryoho. Cancer & chemotherapy, 31, 1, 61, 5, 2004年01月, ［国内誌］
日本語, 研究論文（学術雑誌）, Clinical effects and safety of cefozopran (CZOP) were evaluated by the Okayama Bone Marrow Transplantation Group. Twenty-five patients expected to experience febrile neutropenia during induction chemotherapy or consolidation chemotherapy of acute leukemia were enrolled between July 2000 and November 2002. CZOP was administrated by drip infusion at 4g/day bid for a minimum of 3 days. The clinical effects and safety were evaluated in 20 patients with fever of 37.5 degrees C or more from a clinically suspected infection. The underlying disease was acute myeloid leukemia in 17 patients, acute lymphoid leukemia in 1 and acute promyelogeneous leukemia in 1. The complicating infections were sepsis and suspected sepsis. Clinical efficacy was excellent in 11 patients, good in 1, fair in 2 and poor in 6, with an efficacy rate of 60.0%. The efficacy rate in patients whose albumin levels before therapy were less than 3.8 g/dl was 37.5%, whereas the rate in patients whose albumin levels before therapy were between 3.8 g/dl and 5.3 g/dl was 80.0%. The efficacy rate in patients whose neutrophil counts before therapy were less than 100/microliter was 50.0%, whereas the rate in patients whose neutrophil counts after therapy were less than 100/microliter was 53.8%. The efficacy rate in patients whose neutrophil counts both before and after therapy were less than 100/microliter was 37.5%. Side effect of exanthema was observed in 1 patient. These results indicate that CZOP is an effective and safe antibiotic for the treatment of febrile neutropenia in patients with hematological malignancies.

GVHDとGVL　　　　　　　　　　　　　　　
豊嶋 崇徳
分子細胞治療, 3, 5, 512, 517, 2004年
日本語, 研究論文（学術雑誌）

GVHDの新しい理解
豊嶋 崇徳
最新医学, 59, 1, 128, 134, 最新医学社, 2004年
日本語, 研究論文（学術雑誌）

Role of CXCR3-induced donor T-cell migration in acute GVHD
U Duffner, B Lu, GC Hildebrandt, T Teshima, DL Williams, P Reddy, R Ordemann, SG Clouthier, K Lowler, C Liu, C Gerard, KR Cooke, JLM Ferrara
EXPERIMENTAL HEMATOLOGY, 31, 10, 897, 902, 2003年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect
SG Clouthier, KR Cooke, T Teshima, KP Lowler, C Liu, K Connolly, JLM Ferrara
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 9, 9, 592, 603, 2003年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Impaired thymic negative selection causes autoimmune graft-versus-host disease
T Teshima, P Reddy, C Liu, D Williams, KR Cooke, JLM Ferrara
BLOOD, 102, 2, 429, 435, 2003年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays
T Ichiba, T Teshima, R Kuick, DE Misek, C Liu, Y Takada, Y Maeda, P Reddy, DL Williams, SM Hanash, JLM Ferrara
BLOOD, 102, 2, 763, 771, 2003年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Over-expression of the dominant-negative isoform of Ikaros confers resistance to dexamethasone-induced and anti-IgM-induced apoptosis
N Sezaki, F Ishimaru, M Takata, T Tabayashi, K Nakase, T Kozuka, K Fujii, H Nakayama, T Teshima, M Harada, M Tanimoto
BRITISH JOURNAL OF HAEMATOLOGY, 121, 1, 165, 169, 2003年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects
P Reddy, T Teshima, G Hildebrandt, DL Williams, C Liu, KR Cooke, JLM Ferrara
BLOOD, 101, 7, 2877, 2885, 2003年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Pulmonary infiltration with eosinophilia syndrome complicated with non-Hodgkin’s lymphoma of B cell lineage
Fujii M, Tanimoto Y, Kiguchi T, Takehara H, Fujimori Y, Teshima T, Kanehiro A, Shinagawa K, Tada S, Kataoka M, Tanimoto M
Allergology International, 52, 3, 161, 164, Blackwell Publishing, 2003年, ［査読有り］
英語, 研究論文（学術雑誌）

成人Ｂ細胞性急性リンパ性白血病(ALL L3)における長期予後の改善　　　　　　　　　　　　　　　
石丸文彦, 近藤英生, 藤井伸治, 豊嶋崇徳, 品川克至, 池田和眞, 谷本光音
内科専門医会誌, 15, 4, 618, 621, 2003年, ［査読有り］
[症例報告]

The pathophysiology of acute graft-versus-host disease　　　　　　　　　　　　　　　
International Journal of Hematology, 78, 181, 187, 2003年
英語, 研究論文（学術雑誌）

Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization
T Kozuka, K Ikeda, T Teshima, K Kojima, K Matsuo, A Bessho, K Sunami, Y Hiramatsu, Y Maeda, T Noguchi, K Yamamoto, N Fujii, T Imai, K Takenaka, K Shinagawa, F Ishimaru, K Niiya, N Koide, M Tanimoto, M Harada
TRANSFUSION, 42, 11, 1514, 1522, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation
P Reddy, T Teshima, G Hildebrandt, U Duffner, Y Maeda, KR Cooke, JLM Ferrara
BLOOD, 100, 9, 3429, 3431, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Acute graft-versus-host disease does not require alloantigen expression on host epithelium
T Teshima, R Ordemann, P Reddy, S Gagin, C Liu, KR Cooke, JLM Ferrara
NATURE MEDICINE, 8, 6, 575, 581, 2002年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Enhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease
R Ordemann, R Hutchinson, J Friedman, SJ Burakoff, P Reddy, U Duffner, TM Braun, C Liu, T Teshima, JLM Ferrara
JOURNAL OF CLINICAL INVESTIGATION, 109, 9, 1249, 1256, 2002年05月, ［査読有り］
英語, 研究論文（学術雑誌）