研究者詳細 - 増子　正義

論文 - 増子　正義

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Registry data analysis of hematopoietic stem cell transplantation on systemic chronic active Epstein–Barr virus infection patients in Japan

Masahide Yamamoto, Maho Sato, Yasushi Onishi, Yoji Sasahara, Hideki Sano, Masayoshi Masuko, Hirohisa Nakamae, Ken‐ichi Matsuoka, Takahide Ara, Kana Washio, Makoto Onizuka, Kenichiro Watanabe, Yoshiyuki Takahashi, Tsuneaki Hirakawa, Miwako Nishio, Chizuko Sakashita, Tohru Kobayashi, Akihisa Sawada, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Hashii, Yoshiko Atsuta, Ayako Arai

American Journal of Hematology 2022年3月

Altered microbiota by a high-fat diet accelerates lethal myeloid hematopoiesis associated with systemic SOCS3 deficiency. 査読国際誌

Kaori Cho, Takashi Ushiki, Hajime Ishiguro, Suguru Tamura, Masaya Araki, Tatsuya Suwabe, Takayuki Katagiri, Mari Watanabe, Yoko Fujimoto, Riuko Ohashi, Yoichi Ajioka, Ippei Shimizu, Shujiro Okuda, Masayoshi Masuko, Yoshimi Nakagawa, Hideyo Hirai, Warren S Alexander, Hitoshi Shimano, Hirohito Sone

iScience 24 ( 10 ) 103117 - 103117 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

DOI： 10.1016/j.isci.2021.103117

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イノツズマブによる再寛解導入に引き続いてブリナツモマブを投与し再移植できたB-ALLの1例

米澤穂高, 布施香子, 水戸部正樹, 武田るい, 諏訪部達也, 片桐隆幸, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

臨床血液 62 ( 10 ) 1526 - 1526 2021年10月

イノツズマブによる再寛解導入に引き続いてブリナツモマブを投与し再移植できたB-ALLの1例

米澤穂高, 布施香子, 水戸部正樹, 武田るい, 諏訪部達也, 片桐隆幸, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

臨床血液 62 ( 10 ) 1526 - 1526 2021年10月

Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis. 査読国際誌

Shuhei Kurosawa, Shohei Mizuno, Yasuyuki Arai, Masayoshi Masuko, Junya Kanda, Kentaro Kohno, Daishi Onai, Takahiro Fukuda, Yukiyasu Ozawa, Yuta Katayama, Masatsugu Tanaka, Kazuhiro Ikegame, Naoyuki Uchida, Tetsuya Eto, Shuichi Ota, Junji Tanaka, Tatsuo Ichinohe, Yoshiko Atsuta, Masamitsu Yanada

Blood cancer journal 11 ( 9 ) 159 - 159 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.

DOI： 10.1038/s41408-021-00553-w

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AMLにおける造血幹細胞移植後1年未満の再発は高い死亡率と相関する(Post-transplant relapse of AML within one year is associated with a high mortality rate)

片桐隆幸, 本宮奈津子, 武田ルイ, 水戸部正樹, 米沢穂高, 諏訪部達也, 布施香子, 柴崎康彦, 瀧澤淳, 曽根博仁, 増子正義

日本血液学会学術集会 83回 PS - 10 2021年9月

WT1ペプチドワクチン投与後のCML患者におけるWT1特異的CTLの持続性と多様性(Persistence and diversity of WT1-specific CTLs in a CML patient vaccinated WT1 peptide)

諏訪部達也, 柴崎康彦, 田村秀, 片桐隆幸, 布施香子, 牛木隆志, 曽根博仁, 成田美和子, 増子正義

日本血液学会学術集会 83回 PS - 1 2021年9月

ドナーリンパ球のコンドロイチン硫酸合成低下はGVHDを軽減する(Genetic manipulation resulting in decreased donor chondroitin sulfate mitigates GVHD in mice)

田村秀, 牛木隆志, 諏訪部達也, 片桐隆幸, 石黒創, 布施香子, 柴崎康彦, 進藤岳郎, 五十嵐道弘, 曽根博仁, 増子正義

日本血液学会学術集会 83回 OS3 - 1 2021年9月

Intensive oral care can reduce bloodstream infection with coagulase-negative staphylococci after neutrophil engraftment in allogeneic hematopoietic stem-cell transplantation. 査読国際誌

Tatsuya Suwabe, Kyoko Fuse, Kouji Katsura, Marie Soga, Takayuki Katagiri, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30 ( 1 ) 475 - 485 2021年7月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually. METHOD: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT. RESULT: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009). CONCLUSION: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS.

DOI： 10.1007/s00520-021-06447-8

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Prognostic value of measurable residual disease at allogeneic transplantation for adults with core binding factor acute myeloid leukemia in complete remission. 査読国際誌

Takaaki Konuma, Tadakazu Kondo, Masayoshi Masuko, Hiroaki Shimizu, Souichi Shiratori, Takahiro Fukuda, Jun Kato, Masashi Sawa, Yukiyasu Ozawa, Shuichi Ota, Naoyuki Uchida, Yoshinobu Kanda, Shinichi Kako, Shin Fujisawa, Kentaro Fukushima, Tatsuo Ichinohe, Yoshiko Atsuta, Masamitsu Yanada

Bone marrow transplantation 56 ( 11 ) 2779 - 2787 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pretransplant measurable residual disease (MRD) has been shown to be associated with relapse incidence following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). However, it remains less clear whether pretransplant MRD status affects transplant outcomes in core binding factor AML (CBF-AML). We retrospectively evaluated the effect of pretransplant MRD, which was measured by a polymerase chain reaction of RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcripts, on transplant outcomes for a cohort of 959 adult patients with t(8;21) or inv(16) AML treated by allogeneic HCT during complete remission (CR), between 2000 and 2018. Multivariate analysis showed the absence of pretransplant MRD was significantly associated with lower relapse (hazard ratio [HR], 0.46; P < 0.001), treatment failure (HR, 0.66; P = 0.004), and overall mortality (HR, 0.72; P = 0.037) among patients with t(8;21). However, pretransplant MRD negativity was not associated with relapse (HR, 0.73; P = 0.420), treatment failure (HR, 0.64; P = 0.063), or overall mortality (HR, 0.69; P = 0.149) among patients with inv(16). In subgroup analysis, pretransplant MRD status significantly affected relapse and LFS only in patients with t(8;21) undergoing allogeneic HCT during CR2. In conclusion, our data demonstrate the different prognostic values of pretransplant MRD for CBF-AML, highlighting the need to develop effective therapeutic strategies for such MRD-positive patients.

DOI： 10.1038/s41409-021-01409-4

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Single cord blood transplantation for acute myeloid leukemia patients aged 60 years or older: a retrospective study in Japan. 査読国際誌

Masamichi Isobe, Takaaki Konuma, Masayoshi Masuko, Naoyuki Uchida, Shigesaburo Miyakoshi, Yasuhiro Sugio, Shuro Yoshida, Masatsugu Tanaka, Yoshiko Matsuhashi, Norimichi Hattori, Makoto Onizuka, Nobuyuki Aotsuka, Yasushi Kouzai, Atsushi Wake, Takafumi Kimura, Tatsuo Ichinohe, Yoshiko Atsuta, Masamitsu Yanada

Annals of hematology 100 ( 7 ) 1849 - 1861 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The availability of alternative donor sources could allow elderly patients to receive allogeneic hematopoietic cell transplantation (HCT). We retrospectively evaluated the outcomes of single-unit cord blood transplantation (CBT) in 1577 patients aged ≥60 years with acute myeloid leukemia (AML) in Japan between 2002 and 2017. In total, 990 (63%) patients were not in complete remission (CR) at the time of CBT. A myeloablative conditioning regimen (52%) and calcineurin inhibitor (CI) + mycophenolate mofetil (MMF)-based graft-versus-host disease (GVHD) prophylaxis (45%) were more commonly used. With a median follow-up for survivors of 31 months, the probability of overall survival and the cumulative incidence of leukemia-related mortality at 3 years was 31% and 29%, respectively. The cumulative incidence of non-relapse mortality (NRM) at 100 days and 3 years were 24% and 41%, respectively. The cumulative incidences of grade II-IV and grade III-IV acute GVHD at 100 days and extensive chronic GVHD at 2 years were 44%, 16%, and 14%, respectively. The cumulative incidence of neutrophil engraftment was 80% at 42 days. Results of multivariate analysis indicated that the following factors were significantly associated with higher overall mortality: performance status ≥1, hematopoietic cell transplantation-specific comorbidity index ≥3, adverse cytogenetics, extramedullary disease at diagnosis, and non-CR status at CBT. By contrast, female sex, HLA disparities ≥2, mycophenolate mofetil-based GVHD prophylaxis, and recent CBT were significantly associated with lower overall mortality. In conclusion, single CBT offers a curative option for AML patients aged ≥60 years with careful patient selection.

DOI： 10.1007/s00277-021-04464-5

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陰茎・陰嚢病変を合併した精巣原発DLBCL

水戸部正樹, 武田ルイ, 米沢穂高, 田村秀, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 井上佳菜子, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

臨床血液 62 ( 6 ) 668 - 668 2021年6月

同種造血幹細胞移植後の慢性GVHDとしての類上皮肉芽腫および多発筋炎

諏訪部達也, 布施香子, 水戸部正樹, 武田ルイ, 米沢穂高, 片桐隆幸, 河本啓介, 牛木隆志, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 大島孝一, 増子正義

臨床血液 62 ( 6 ) 675 - 675 2021年6月

WT1-specific CD8 + cytotoxic T cells with the capacity for antigen-specific expansion accumulate in the bone marrow in MDS. 査読

Tatsuya Suwabe, Yasuhiko Shibasaki, Hiroyuki Sato, Suguru Tamura, Takayuki Katagiri, Hiroki Nemoto, Takuya Kasami, Takashi Kozakai, Ayako Nanba, Toshiki Kitajima, Kyoko Fuse, Takashi Ushiki, Hirohito Sone, Miwako Narita, Masayoshi Masuko

International journal of hematology 113 ( 5 ) 723 - 734 2021年5月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Wilms' tumor 1 (WT1) is a tumor-associated antigen and immunotherapy target in myelodysplastic syndrome (MDS). Further information is needed on the characteristics of WT1-specific CD8 + T cells to develop immunotherapeutic strategies for MDS. To clarify the frequency, distribution, and phenotype of WT1-specific CD8 + T cells, which occur innately in MDS patients, we analyzed paired peripheral blood (PB) and bone marrow (BM) samples from 39 patients with MDS or acute myeloid leukemia with myelodysplasia-related changes. The median frequency of WT1 tetramer-binding CD8 + T cells in the CD8 + T cell population was 0.11% in PB and 0.18% in BM. A further tetramer assay combined with mixed lymphocyte peptide culture (MLPC assay) was used to detect functional WT1-specific CD8 + T cells that could respond to the WT1 peptide. Functional WT1-specific CD8 + T cells were detected in BM in 61% of patients, which was significantly higher than in PB (23%, p = 0.001). The frequency of these cells estimated by the MLPC assay was tenfold higher in BM than in PB. The majority of WT1 tetramer-binding CD8 + T cells in BM had a unique phenotype with co-expression of CD39 and CXCR4. These findings will facilitate the development of novel immunotherapeutic strategies for MDS.

DOI： 10.1007/s12185-021-03083-0

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乾燥人フィブリノゲン製剤の継続輸注で着床・妊娠継続・出産をし得た先天性低フィブリノゲン血症

関義信, 牛木隆志, 増子正義, 瀧澤淳, 曽根博仁, 奥村伸生

日本血栓止血学会誌 32 ( 2 ) 214 - 214 2021年5月

GB療法施行中にHigh-grade B-cell lymphoma with MYC and BCL2 rearrangementsで再燃したFollicular lymphoma(Grade 3A)の2症例

水戸部正樹, 本宮奈津子, 武田ルイ, 米沢穂高, 鈴木隆晴, 諏訪部達也, 片桐隆幸, 河本啓介, 布施香子, 柴崎康彦, 増子正義, 井上佳菜子, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

日本リンパ網内系学会会誌 61 114 - 114 2021年5月

腎障害を有する高悪性度B細胞リンパ腫症例にDA-EPOCH-Rを施行した1例

水戸部正樹, 河本啓介, 鈴木隆晴, 米沢穂高, 田村秀, 諏訪部達也, 根本洋樹, 布施香子, 柴崎康彦, 増子正義, 三好寛明, 大島孝一, 曽根博仁, 瀧澤淳

臨床血液 62 ( 5 ) 532 - 532 2021年5月

ルキソルチニブ・ヒドロキシウレア併用療法が奏効した慢性好中球性白血病(CNL)の1例

武田ルイ, 布施香子, 片桐隆幸, 河本啓介, 柴崎康彦, 瀧澤淳, 成田美和子, 野本信彦, 曽根博仁, 増子正義

臨床血液 62 ( 5 ) 529 - 530 2021年5月

Distinct effects of chondroitin sulfate on hematopoietic cells and the stromal microenvironment in bone marrow hematopoiesis. 査読国際誌

Takayuki Katagiri, Shun Uemura, Takashi Ushiki, Yaeko Nakajima-Takagi, Motohiko Oshima, Tadahisa Mikami, Asami Kawasaki, Hajime Ishiguro, Tomoyuki Tanaka, Hirohito Sone, Hiroshi Kitagawa, Michihiro Igarashi, Atsushi Iwama, Masayoshi Masuko

Experimental hematology 96 52 - 62 2021年4月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The bone marrow (BM) microenvironment, known as the BM niche, regulates hematopoiesis but is also affected by interactions with hematopoietic cells. Recent evidence indicates that extracellular matrix components are involved in these interactions. Chondroitin sulfate (CS), a glycosaminoglycan, is a major component of the extracellular matrix; however, it is not known whether CS has a physiological role in hematopoiesis. Here, we analyzed the functions of CS in hematopoietic and niche cells. CSGalNAcT1, which encodes CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, was highly expressed in hematopoietic stem and progenitor cells (HSPCs) and endothelial cells (ECs), but not in mesenchymal stromal cells (MSCs) in BM. In T1 knockout (T1KO) mice, a greater number of HSPCs existed compared with the wild-type (WT), but HSPCs from T1KO mice showed significantly impaired repopulation in WT recipient mice on serial transplantation. RNA sequence analysis revealed the activation of IFN-α/β signaling and endoplasmic reticulum stress in T1KO HSPCs. In contrast, the number of WT HSPCs repopulated in T1KO recipient mice was larger than that in WT recipient mice after serial transplantation, indicating that the T1KO niche supports repopulation of HSPCs better than the WT niche. There was no obvious difference in the distribution of vasculature and MSCs between WT and T1KO BM, suggesting that CS loss alters vascular niche functions without affecting its structure. Our results revealed distinct roles of CS in hematopoietic cells and BM niche, indicating that crosstalk between these components is important to maintain homeostasis in BM.

DOI： 10.1016/j.exphem.2021.02.003

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DA-EPOCH-R therapy for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in a patient with renal dysfunction. 査読

Masaki Mitobe, Keisuke Kawamoto, Takaharu Suzuki, Tatsuya Suwabe, Yasuhiko Shibasaki, Masayoshi Masuko, Kanako Inoue, Hiroaki Miyoshi, Koichi Ohshima, Hirohito Sone, Jun Takizawa

Journal of clinical and experimental hematopathology : JCEH 61 ( 1 ) 42 - 47 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit lymphoma, has been reported as refractory to R-CHOP therapy and requires more intensive regimens. However, intensive and safe regimens for patients with renal dysfunction are unknown. Herein, we report the successful use of DA-EPOCH-R therapy for double-hit lymphoma in a 64-year-old man with renal dysfunction. The patient had lymphoma-induced bilateral ureteral obstruction. Although renal dysfunction remained after removing the obstruction using R-CHOP therapy, we completed six cycles of DA-EPOCH-R therapy without any major adverse events. DA-EPOCH-R therapy may be a safe regimen for renal dysfunction patients.

DOI： 10.3960/jslrt.20043

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