研究者詳細 - 淺田　騰

論文 - 淺田　騰

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Antitumor activity of α-pinene in T-cell tumors. 査読国際誌

Masaya Abe, Noboru Asada, Maiko Kimura, Chie Fukui, Daisuke Yamada, Ziyi Wang, Masayuki Miyake, Takeshi Takarada, Mitsuaki Ono, Michinori Aoe, Wataru Kitamura, Masayuki Matsuda, Takashi Moriyama, Akifumi Matsumura, Yoshinobu Maeda

Cancer science 2024年1月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.

DOI： 10.1111/cas.16086

Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T-cell therapy. 査読国際誌

Wataru Kitamura, Noboru Asada, Yusuke Naoi, Masaya Abe, Hideaki Fujiwara, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

British journal of haematology 202 ( 2 ) 294 - 307 2023年3月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T-cell therapy, an emerging therapy for relapsed or refractory diffuse large B-cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T-cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T-cell infusion in patients with PC. Cytokine analyses after CAR T-cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation-related cytokines on day 28 after CAR T-cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation-related cytokines in the BM following CAR T-cell infusion are associated with subsequent PC.

DOI： 10.1111/bjh.18747

Recent advances in “sickle and niche” research - Tribute to Dr. Paul S Frenette - 査読

Lidiane S. Torres, Noboru Asada, Mitchell J. Weiss, Andreas Trumpp, Toshio Suda, David T. Scadden, Keisuke Ito

Stem Cell Reports 17 ( 7 ) 1509 - 1535 2022年7月

Treatment outcomes of IgG4-producing marginal zone B-cell lymphoma: a retrospective case series 査読

Yuichi Sumii, Noboru Asada, Yasuharu Sato, Koh-ichi Ohshima, Masanori Makita, Yusuke Yoshimoto, Yuka Sogabe, Kenji Imajo, Yusuke Meguri, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

International Journal of Hematology 112 ( 6 ) 780 - 786 2020年8月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

IgG4-producing marginal zone B-cell lymphomas (MZLs) have been recently proposed as a subtype of MZLs. Despite the abundant literature on pathophysiological features of this type of lymphoma, only a few retrospective studies pertaining to the treatment outcomes have been reported, and its prognosis remains unclear. We retrospectively analyzed seven patients with IgG4-producing MZLs diagnosed at our institute, with specific reference to treatment and outcomes. The median age was 69.0 years (55-79), and all were males. The median follow-up period was 66.6 months (8-121). All patients had localized disease; four patients had tumors of the ocular adnexa, whereas two had retroperitoneal tumors. Five patients were treated with irradiation (30 Gy/15 fr) (n = 4) or surgery (n = 1), resulting in tumor reduction. Two patients were treated by chemotherapy or irradiation. Among them, one commenced rituximab monotherapy, which led to an inadequate reduction of the tumor. Subsequent irradiation induced complete response (CR). The other patient experienced repeated relapses during follow-up and finally achieved CR by combination chemotherapy. Treatment was well tolerated in all cases, and none of the patients showed disease progression at the last follow-up visit. Our results indicate that the standard treatments for MZLs are generally appropriate for IgG4-producing MZL.

DOI： 10.1007/s12185-020-02968-w

その他リンク： http://link.springer.com/article/10.1007/s12185-020-02968-w/fulltext.html

Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression 査読

Qiaozhi Wei, Fumio Nakahara, Noboru Asada, Dachuan Zhang, Xin Gao, Chunliang Xu, Alan Alfieri, N. Patrik Brodin, Samuel E. Zimmerman, Jessica C. Mar, Chandan Guha, Wenjun Guo, Paul S. Frenette

Developmental Cell 53 ( 5 ) 503 - 513.e5 2020年6月

Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11 査読国際誌

Yuichi Ishikawa, Naomi Kawashima, Yoshiko Atsuta, Isamu Sugiura, Masashi Sawa, Nobuaki Dobashi, Hisayuki Yokoyama, Noriko Doki, Akihiro Tomita, Toru Kiguchi, Shiro Koh, Heiwa Kanamori, Noriyoshi Iriyama, Akio Kohno, Yukiyoshi Moriuchi, Noboru Asada, Daiki Hirano, Kazuto Togitani, Toru Sakura, Maki Hagihara, Tatsuki Tomikawa, Yasuhisa Yokoyama, Norio Asou, Shigeki Ohtake, Itaru Matsumura, Yasushi Miyazaki, Tomoki Naoe, Hitoshi Kiyoi

Blood Advances 4 ( 1 ) 66 - 75 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Society of Hematology

<title>Key Points</title>
KIT exon 17 mutation is a poor prognostic factor in AML patients with RUNX1-RUNX1T1, but not in those with CBFB-MYH11. NRAS mutation is a poor prognostic factor in AML patients with CBFB-MYH11.

DOI： 10.1182/bloodadvances.2019000709

Adult T-cell Leukemia-lymphoma with Primary Breast Involvement: A Case Report and Literature Review 査読

Hiroki Kobayashi, Noboru Asada, Takuro Igawa, Masaya Abe, Yusuke Meguri, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

Internal Medicine 59 ( 21 ) 2757 - 2761 2020年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Society of Internal Medicine

Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival.

DOI： 10.2169/internalmedicine.5077-20

Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche 査読

Maria Maryanovich, Ali H. Zahalka, Halley Pierce, Sandra Pinho, Fumio Nakahara, Noboru Asada, Qiaozhi Wei, Xizhe Wang, Paul Ciero, Jianing Xu, Avigdor Leftin, Paul S. Frenette

Nature Medicine 24 ( 6 ) 782 - 791 2018年6月

Regulation of malignant hematopoiesis by bone marrow microenvironment 査読

Noboru Asada

Frontiers in Oncology 8 119 2018年4月

The hematopoietic stem cell niche: from embryo to adult. 査読

Gao X, Xu C, Asada N, Frenette PS

Development (Cambridge, England) 145 ( 2 ) 2018年1月

A non-cell-autonomous role for Pml in the maintenance of leukemia from the niche. 査読

Guarnerio J, Mendez LM, Asada N, Menon AV, Fung J, Berry K, Frenette PS, Ito K, Pandolfi PP

Nature communications 9 ( 1 ) 66 2018年1月

Complexity of bone marrow hematopoietic stem cell niche 査読

Noboru Asada, Shoichiro Takeishi, Paul S. Frenette

INTERNATIONAL JOURNAL OF HEMATOLOGY 106 ( 1 ) 45 - 54 2017年7月

Differential cytokine contributions of perivascular haematopoietic stern cell niches 査読

Noboru Asada, Yuya Kunisaki, Halley Pierce, Zichen Wang, Nicolas F. Fernandez, Alexander Birbrair, Avi Ma'ayan, Paul S. Frenette

NATURE CELL BIOLOGY 19 ( 3 ) 214 - 223 2017年3月

G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE(2) 査読

Yuko Kawano, Chie Fukui, Masakazu Shinohara, Kanako Wakahashi, Shinichi Ishii, Tomohide Suzuki, Mari Sato, Noboru Asada, Hiroki Kawano, Kentaro Minagawa, Akiko Sada, Tomoyuki Furuyashiki, Satoshi Uematsu, Shizuo Akira, Toshimitsu Uede, Shuh Narumiya, Toshimitsu Matsui, Yoshio Katayama

BLOOD 129 ( 5 ) 587 - 597 2017年2月

Communication of bone cells with hematopoiesis, immunity and energy metabolism. 査読国際誌

Asada N, Sato M, Katayama Y

BoneKEy reports 4 748 - 748 2015年

Regulation of hematopoiesis in endosteal microenvironments 査読

Noboru Asada, Yoshio Katayama

INTERNATIONAL JOURNAL OF HEMATOLOGY 99 ( 6 ) 679 - 684 2014年6月

Osteocytes Regulate Primary Lymphoid Organs and Fat Metabolism 査読

Mari Sato, Noboru Asada, Yuko Kawano, Kanako Wakahashi, Kentaro Minagawa, Hiroki Kawano, Akiko Sada, Kyoji Ikeda, Toshimitsu Matsui, Yoshio Katayama

CELL METABOLISM 18 ( 5 ) 749 - 758 2013年11月

Matrix-Embedded Osteocytes Regulate Mobilization of Hematopoietic Stem/Progenitor Cells 査読

Noboru Asada, Yoshio Katayama, Mari Sato, Kentaro Minagawa, Kanako Wakahashi, Hiroki Kawano, Yuko Kawano, Akiko Sada, Kyoji Ikeda, Toshimitsu Matsui, Mitsune Tanimoto

CELL STEM CELL 12 ( 6 ) 737 - 747 2013年6月

Random skin biopsy and bone marrow biopsy for diagnosis of intravascular large B cell lymphoma 査読

Kosei Matsue, Noboru Asada, Jun Odawara, Takayoshi Aoki, Shun-ichi Kimura, Kan-ichi Iwama, Hideaki Fujiwara, Masayuki Yamakura, Masami Takeuchi

ANNALS OF HEMATOLOGY 90 ( 4 ) 417 - 421 2011年4月

Role for vitamin D receptor in the neuronal control of the hematopoietic stem cell niche 査読

Yuriko Kawamori, Yoshio Katayama, Noboru Asada, Kentaro Minagawa, Mari Sato, Atsuo Okamura, Manabu Shimoyama, Kimie Nakagawa, Toshio Okano, Mitsune Tanimoto, Shigeaki Kato, Toshimitsu Matsui

BLOOD 116 ( 25 ) 5528 - 5535 2010年12月

Progressive osteosclerosis and visceral calcification after cord blood transplantation 査読

Noboru Asada, Shinichi Ishii, Kanako Wakahashi, Hiroki Kawano, Yuriko Kawamori, Shinichiro Nishikawa, Kentaro Minagawa, Atsuo Okamura, Manabu Shimoyama, Yoshio Katayama, Yoshitake Hayashi, Tomoo Itoh, Mitsune Tanimoto, Toshimitsu Matsui

INTERNATIONAL JOURNAL OF HEMATOLOGY 91 ( 3 ) 542 - 545 2010年4月

Use of random skin biopsy for diagnosis of intravascular large B-Cell lymphoma 査読

Noboru Asada, Jun Odawara, Shun-Ichi Kimura, Takatoshi Aoki, Masayuki Yamakura, Masami Takeuchi, Reiko Seki, Atsushi Tanaka, Kosei Matsue

MAYO CLINIC PROCEEDINGS 82 ( 12 ) 1525 - 1527 2007年12月

血液疾患患者におけるミカファンギン投与による侵襲性トリコスポロン症のbreakthrough感染症の検討

淺田騰, 瓜生英尚, 小関美保子, 竹内正美, 福田隆浩, 杉山暖子, 前田嘉信, 山筋好子, 進藤基博, 今村豊, 末永孝生

臨床血液 47 ( 9 ) 1144 2006年9月

Successful treatment of breakthrough Trichosporon asahii fungemia with voriconazole in a patient with acute myeloid leukemia 査読

Noboru Asada, Hidetaka Uryu, Mihoko Koseki, Masami Takeuchi, Masaru Komatsu, Kosei Matsue

CLINICAL INFECTIOUS DISEASES 43 ( 4 ) E39 - E41 2006年8月

A successful control of cardiac amyloidosis by idecabtagene vicleucel in a patient with relapsed and refractory multiple myeloma: a case report and literature review.

Yayoi Ueda, Toshiki Terao, Nobuharu Fujii, Tatsuji Mino, Saya Kubota, Kenta Hayashino, Kanako Fujiwara, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Hideo Tanaka, Yoshinobu Maeda

International journal of hematology 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 50-year-old Japanese man with penta-drug refractory multiple myeloma (MM) was found to have stage IIIa cardiac immunoglobulin light-chain amyloidosis before idecabtagene vicleucel (ide-cel) therapy. Ide-cel therapy was started after careful consideration and hospital ethics committee approval. Grade 3 cytokine release syndrome and atrial flutter occurred in the acute phase after ide-cel infusion, but these were well-tolerated with supportive care in the intensive care unit. The patient achieved stringent complete response at day 60 and cardiac response at 9 months after ide-cel infusion with the addition of catheter ablation for sustained atrial flutter on day 133. He has maintained both hematological and cardiac remission for over 1 year since ide-cel therapy. This case highlights the effectiveness of ide-cel for disease control in heavily pretreated MM with cardiac amyloidosis.

DOI： 10.1007/s12185-025-04016-x

Therapeutic impact of mesenchymal stem cells on idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation.

Chihiro Kamoi, Toshiki Terao, Yui Kambara, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda, Ken-Ichi Matsuoka

International journal of hematology 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stem cells (MSCs) effectively treat steroid-refractory acute graft-versus-host disease (aGVHD). However, their impact on patients with both steroid-refractory aGVHD (SR-aGVHD) and idiopathic pneumonia syndrome (IPS) is unclear. This retrospective study analyzed 24 patients who received MSCs as a secondary treatment for SR-aGVHD, including 6 who also had IPS. The 180-day overall survival rate was 52.0%, with a relapse rate of 13.3% and non-relapse mortality at 34.7%. The clinical course was compared between the six patients with concurrent IPS and SR-aGVHD who received MSCs and the 36 IPS patients who did not receive MSCs. The 6 MSC-treated patients had a higher 2-year overall survival rate than the control group, at 83.3% versus 61.1%, with all patients showing reduced oxygen requirements and improved imaging findings. Among the five patients who survived longer than 2 months after MSC therapy, the median time to complete oxygen therapy was 28 days, and steroid doses were reduced by 25% at the 2-month mark. Some patients showed improved pulmonary function after MSC therapy. These findings support MSCs as a promising treatment for SR-aGVHD and suggest potential benefits in IPS.

DOI： 10.1007/s12185-025-04013-0

Safety of hematopoietic stem cell donation from young related donors following the lowering of the age of legal adulthood in Japan.

Tsuneaki Hirakawa, Hiromasa Yabe, Masayuki Hino, Noriko Doki, Satoshi Yoshihara, Shuichi Ota, Takahiro Fukuda, Hirohisa Nakamae, Jun Ishikawa, Yuta Hasegawa, Tetsuya Nishida, Noboru Asada, Hidekazu Nishikii, Toshiro Kawakita, Masayoshi Masuko, Yasuo Mori, Toshihiko Ando, Kazuhiko Ikeda, Marie Ohbiki, Yoshiko Atsuta, Nobuhiro Tsukada, Ryu Yanagisawa

International journal of hematology 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The Japanese government's recent lowering of the legal adult age to 18 may prompt reconsideration of the minimum age for donors in the Japan Marrow Donor Program. To provide foundational data for decision-makers, this retrospective study analyzed the safety of hematopoietic stem cell donation among 1999 related donors aged 18 to 24 years, using data from the Japanese Data Center for Hematopoietic Cell Transplantation. Severe adverse events (SAEs) occurred in 1.0% of all donors, with no significant difference between those aged 18 to 19 (0.7%) and those aged 20 to 24 (1.1%) (P = 0.59). Risk factors for SAEs included ongoing asthma treatment (HR 34.6, 95% CI 2.29-524.00, P < 0.01), history of asthma (HR 11.3, 95% CI 2.46-51.70, P < 0.01), and female sex (HR 4.64, 95% CI 1.51-14.20, P < 0.01). However, age of 18 to 19 was not a significant risk factor (HR 0.53, 95% CI 0.14-2.01, P = 0.35). These results indicate that stem cell donation safety in 18- to 19-year-old donors is comparable to that in 20- to 24-year-olds, with increased risks linked to asthma and female sex.

DOI： 10.1007/s12185-025-04007-y

Improved Transplant Outcomes With Alternative Donors in Myelofibrosis: A 20-Year Japanese Registry Analysis of Donor Sources and the Impact of Ruxolitinib. 査読国際誌

Kazuki Sakatoku, Hirohisa Nakamae, Makoto Murata, Yutaka Shimazu, Katsuto Takenaka, Fumihiko Kimura, Naoyuki Uchida, Tetsuya Nishida, Takahiro Fukuda, Noriko Doki, Jun Ishikawa, Emiko Sakaida, Keisuke Kataoka, Shuichi Shirane, Masatsugu Tanaka, Hikaru Kobayashi, Masashi Sawa, Toshio Wakayama, Noboru Asada, Yasufumi Uehara, Makoto Yoshimitsu, Junya Kanda, Marie Ohbiki, Yoshiko Atsuta, Takayoshi Tachibana

American journal of hematology 100 ( 7 ) 1259 - 1263 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study of 308 myelofibrosis patients shows that in recent years (2013-2019), alternative donors (mismatched unrelated donors and cord blood) achieved survival rates comparable to HLA-matched donors-a significant improvement compared to earlier years (2000-2012) when outcomes differed substantially. Ruxolitinib showed significant benefits in older patients (≥ 57), particularly with mismatched unrelated donors. Cord blood transplantation outcomes improved with MMF-based GVHD prophylaxis. These findings suggest optimized strategies combining both age-specific and donor-specific approaches can maximize transplant success in myelofibrosis patients.

DOI： 10.1002/ajh.27699

Adverse Impact of Pre-Transplant Liver Dysfunction in Allogeneic Hematopoietic Cell Transplantation. 査読国際誌

Yukiko Misaki, Masaharu Tamaki, Ryu Yanagisawa, Noriko Doki, Naoyuki Uchida, Masatsugu Tanaka, Tetsuya Nishida, Masashi Sawa, Yuta Hasegawa, Shuichi Ota, Makoto Onizuka, Sakata-Yanagimoto Mamiko, Yuta Katayama, Noboru Asada, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Yoshinobu Kanda, Kimikazu Yakushijin, Hideki Nakasone

American journal of hematology 100 ( 5 ) 821 - 829 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although the hematopoietic cell transplantation (HCT)-comorbidity index (HCT-CI) score is associated with an increased risk of mortality after allogeneic HCT, it remains unclear how pre-HCT liver dysfunction affects clinical outcomes. We retrospectively compared clinical HCT outcomes among four groups stratified according to the presence of HCT-CI liver and other organ scores, using a Japan transplant registry database between 2010 and 2020. Of the 14235 recipients, 1527 tested positive for an HCT-CI liver score including HBV or HCV hepatitis (n = 503). The 5-year overall survival (OS) was significantly lower in the HCT-CI liver(+) other(+) and HCT-CI liver(-) other(+) groups compared to the HCT-CI liver(+) other(-) and HCT-CI liver(-) other(-) groups [49.9% vs. 59% vs. 66.5% vs. 68.3%, p < 0.001]. A multivariate analysis showed that both the HCT-CI liver(+) other(+) [HR 1.62, p < 0.001] and HCT-CI liver(-) other(+) groups [HR 1.21, p < 0.001] were significantly associated with inferior OS. Similarly, both the HCT-CI liver(+) other(+) [HR 1.89, p < 0.001] and liver(-) other(+) groups [HR 1.26, p < 0.001] were significantly associated with an increased risk of NRM. On the other hand, the HCT-CI liver(+) other(-) group was not associated with either OS or NRM. Separately analyzing the subcohorts with or without HCT-CI other scores, the presence of an HCT-CI liver score alone did not affect survival, while the co-presence of pretransplant liver dysfunction seemed to synergistically increase the adverse impact on OS and NRM among recipients with other organ comorbidities. Further studies will be needed to identify optimal strategies for recipients with pretransplant liver dysfunction.

DOI： 10.1002/ajh.27652

Association of FLT3-ITD and NPM1 mutations with outcomes of allogeneic hematopoietic cell transplantation in acute myeloid leukemia. 査読国際誌

Masamitsu Yanada, Satoshi Yamasaki, Hiroki Hosoi, Shohei Mizuno, Kaito Harada, Noriko Doki, Shin-Ichiro Fujiwara, Nobuhiro Hiramoto, Yuta Hasegawa, Kazuya Ishiwata, Tetsuya Nishida, Noboru Asada, Takuma Suzuki, Mamiko Sakata-Yanagimoto, Naoyuki Uchida, Junya Kanda, Makoto Yoshimitsu, Yoshinobu Kanda, Takahiro Fukuda, Marie Ohbiki, Yoshiko Atsuta, Takaaki Konuma

Bone marrow transplantation 60 ( 6 ) 894 - 896 2025年4月

Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up. 国際誌

Toshihiko Matsuo, Takehiro Tanaka, Noboru Asada, Mikako Obika, Ryotaro Omichi, Keiji Iwatsuki

Cureus 17 ( 4 ) e82348 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 × 103/µL, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy.

DOI： 10.7759/cureus.82348

Markedly elevated serum level of presepsin in agranulocytosis with hematologic malignancy: A potential prognostic factor in a single-institution retrospective study after granulocyte transfusion. 査読国際誌

Takuya Fukumi, Keiko Fujii, Wataru Kitamura, Kazuhiro Ikeuchi, Naomi Asano, Akira Yamamoto, Hiroki Kobayashi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Laboratory medicine 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: No established criteria exist for assessing the effectiveness of granulocyte transfusion (GTX) or biomarkers for predicting fatal infections in neutropenia. This study aimed to assess whether a novel sepsis marker, presepsin (P-SEP), is a useful prognostic indicator during GTX. METHODS: We collected frozen serum from 8 patients who had undergone GTX between September 2022 and October 2023 and measured their P-SEP levels. We compared these results with clinical records and assessed the alterations before and after GTX and their association with prognosis. RESULTS: The post-transfusion neutrophil count increased in all cases. In 5 of 8 patients (62.5%), P-SEP levels were reduced 1 day after GTX. Pretransfusion P-SEP levels were statistically significantly lower in the group of patients who survived and overcame infection after transfusion (GTX-survived) than in the group of patients who did not survive (GTX-nonsurvived) (1493 pg/mL vs 6658 pg/mL, P =.04). Transfused cell counts and changes in P-SEP levels 1 day after GTX were better in the GTX-survived group than in the GTX-nonsurvived group, although the difference was not statistically significant. DISCUSSION: Presepsin is a biomarker that can be assessed in patients undergoing GTX for agranulocytosis. A clinically significant increase in P-SEP levels before GTX may indicate ineffective GTX and an unfavorable prognosis.

DOI： 10.1093/labmed/lmae118

Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome. 査読国際誌

Takaaki Konuma, Machiko Fujioka, Kyoko Fuse, Hiroki Hosoi, Yosuke Masamoto, Noriko Doki, Naoyuki Uchida, Masatsugu Tanaka, Masashi Sawa, Tetsuya Nishida, Jun Ishikawa, Noboru Asada, Hirohisa Nakamae, Yuta Hasegawa, Makoto Onizuka, Takeshi Maeda, Takahiro Fukuda, Koji Kawamura, Yoshinobu Kanda, Marie Ohbiki, Yoshiko Atsuta, Hidehiro Itonaga

Transplantation and cellular therapy 31 ( 6 ) 388.e1-388.e14 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. OBJECTIVE: This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT. STUDY DESIGN: Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4,140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022. RESULTS: Multivariate analysis showed that early (days 0-4) and late (days 5-10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = 0.002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = 0.007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = 0.015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type. CONCLUSION: These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS.

DOI： 10.1016/j.jtct.2025.03.010

BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells 査読国際誌

Mitsuaki Ono, Ikue Tosa, Anh Tuan Dang, Ziyi Wang, Maiko Kimura, Wakana Kitagawa, Kei Ishibashi, Hang Thuy Do, Kun Zhao, Emilio Satoshi Hara, Noboru Asada, Takashi Nagasawa, Toshitaka Oohashi, Naoya Ohara, Takuo Kuboki

Blood Advances 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Society of Hematology

Ectopic bone marrow (eBM) holds tremendous potential as an artificial organ, serving not only in stem cell transplantation therapies but also as a controlled experimental system for analyzing cellular dynamics and interactions between cells and the matrix during the formation, maintenance, and aging of bone marrow (BM). Although bone morphogenetic protein (BMP)-2 has been reported to induce eBM formation, it remains unproven whether BMP-2 induced eBM (BMP-eBM) can provide a functional BM niche that is comparable to native BM in long bones (LB-BM). In this study, through the use of single-cell RNA sequencing and transplantation models, we demonstrate for the first time that BMP-eBM displays a microstructure, cellular composition, and functional hematopoiesis similar to LB-BM. BMP-eBM establishes an optimized microenvironment capable of supporting hematopoietic stem cells (HSCs) and CXC-chemokine-ligand-12 (CXCL12)-abundant reticular (CAR) cells, which are critical components of the BM niche. Significantly, BMP-eBM was able to restore survival in irradiated mice. Through parabiosis and cell transplantation experiments, we identified that in situ adipose tissue-derived CD51highCxcl12-GFP- cells are the principal source of CAR cells within BMP-eBM. Furthermore, BMP-eBM can be isolated and, after preconditioning, re-transplanted as an independent, functional hematopoietic organ. In conclusion, our study confirms that BMP-eBM functions effectively as a hematopoietic organ, capable of supporting and maintaining a functional BM niche. These findings underscore BMP-2 as a crucial molecule for eBM generation and suggest its potential for addressing BM-related diseases and for use as a platform for in vitro and ex vivo biomedical applications.

DOI： 10.1182/bloodadvances.2024014062

A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD. 査読国際誌

Wataru Kitamura, Keiko Fujii, Mitsuru Tsuge, Toshiharu Mitsuhashi, Hiroki Kobayashi, Chihiro Kamoi, Akira Yamamoto, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Nobuharu Fujii, Yoshinobu Maeda

Annals of hematology 104 ( 3 ) 1917 - 1929 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072.

DOI： 10.1007/s00277-025-06269-2

Myelodysplastic neoplasms with repeating TAFRO syndrome-like symptoms. 査読

Kenta Hayashino, Nobuharu Fujii, Tomohiro Nagano, Daisuke Ikeda, Kanako Fujiwara, Risa Hashida, Wataru Kitamura, Hiroki Kobayashi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

International journal of hematology 121 ( 5 ) 706 - 711 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

TAFRO syndrome is a systemic disease characterized by thrombocytopenia, anasarca, fever, systemic inflammation, reticulin fibrosis, renal insufficiency, and organomegaly. Although the pathogenesis of TAFRO syndrome remains unknown, it may be associated with cytokine storm and abnormal immune function. Herein, we present a case of a 65-year-old man who was diagnosed with myelodysplastic neoplasms (MDS) with repeating TAFRO syndrome-like symptoms. At ages 59 and 63 years, he developed TAFRO syndrome and was treated with immunosuppressive therapy, which improved these symptoms. At age 65 years, he had TAFRO syndrome-like symptoms with pancytopenia, chromosomal abnormalities, and dysplasia. The patient was subsequently diagnosed with MDS and treated with methylprednisolone, rituximab, bortezomib, and tocilizumab. His MDS-related and TAFRO syndrome-like symptoms simultaneously improved following treatment. Although the patient was not diagnosed with MDS at the first and second events, chromosomal abnormalities were detected, revealing increased clonal cells. MDS can be complicated by immune disorders associated with increased malignant clonal cells. Additionally, patients with MDS exhibit hypercytokinemia, including interleukin-6 and vascular endothelial growth factor. This case indicates that increased clonal cells and hypercytokinemia caused by MDS may lead to abnormal immune function and induce TAFRO syndrome-like symptoms.

DOI： 10.1007/s12185-025-03937-x

Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma. 国際誌

Hiroki Kobayashi, Ryota Chijimatsu, Yusuke Naoi, Yoshihiro Otani, Ryo Mizuta, Kentaro Fujii, Joji Ishida, Hiroyuki Murakami, Hideki Ujiie, Kazuhiro Ikeuchi, Tomohiro Urata, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Nobuharu Fujii, Ken-Ichi Matsuoka, Yasuharu Sato, Yoshinobu Maeda, Daisuke Ennishi

Blood neoplasia 2 ( 1 ) 100058 - 100058 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive type of lymphoma, most often histologically diagnosed as diffuse large B-cell lymphoma (DLBCL). Recent advancements in single-cell sequencing have elucidated that the diverse germinal center states in systemic DLBCL manifest as tumor cell diversity, intricately linked to variations in the microenvironment. However, detailed characterization of intratumoral heterogeneity reflecting B-cell states in PCNSL remains elusive. Here, we conducted single-cell and spatial multiomic analyses to elucidate the cellular and spatial heterogeneity and the microenvironment in PCNSL. We identified a distinctive lymphoma subpopulation with gene and protein expression similar to that of plasmablasts (PBLs), enriched in some patients with PCNSL. B-cell receptor (BCR) analysis revealed that BCR clonotypes of the PBL signature subpopulation were shared with other subpopulations, suggesting a common origin with other lymphoma cell subtypes. Spatial analysis additionally revealed several localization patterns of PBL signature subpopulations within the tissue, indicating spatial heterogeneity. An expansion study showed that ∼40% of patients with PCNSL had a PBL signature subpopulation, as defined by CD138 immunohistochemistry staining. Additionally, patients with a PBL signature subpopulation and low CD3+ cell infiltration exhibited a worse prognosis. Finally, intercellular communication analysis suggested that the PBL signature subpopulation had distinct cellular interactions with the microenvironment. In summary, our study identified a tumor subpopulation with a PBL signature in PCNSL, suggesting distinct molecular and spatial cross talk with the microenvironment. These findings provided new insights into the biological mechanisms of PCNSL.

DOI： 10.1016/j.bneo.2024.100058

A fatal case of enterovirus A71-induced meningoencephalitis following allogenic hematopoietic stem cell transplantation. 査読国際誌

Yayoi Ueda, Hiroki Kobayashi, Hideaki Fujiwara, Hideharu Hagiya, Risa Hashida, Saya Kubota, Mami Takemoto, Kenta Hayashino, Kanako Fujiwara, Tomohiro Nagano, Ryuichiro Hiyama, Keiko Fujii, Takumi Kondo, Keisuke Seike, Noboru Asada, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Maeda Yoshinobu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 31 ( 4 ) 102630 - 102630 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Enterovirus A71 (EV-A71) is a major pathogen responsible for hand, foot, and mouth disease (HFMD) in infants and children. EV-A71 infection represents an epidemic in the Asia-Pacific region, and can cause serious central nervous system (CNS) infections in immunocompromised patients that can result in paralysis, disability, or death. There have been few reports in the literature concerning EV-A71 CNS infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients. We describe the case of a 63-year-old woman with EV-A71 meningoencephalitis who underwent a second allo-HSCT for relapsed refractory myelodysplastic syndrome. She developed disturbance of consciousness during intubation due to severe pulmonary impairment following allo-HSCT. Despite the absence of pleocytosis in the cerebrospinal fluid, enterovirus was detected in her cerebral spinal fluid using the Biofire® FilmArray® Meningitis/Encephalitis (ME) panel, which was later identified as EV-A71 at a referral center. Despite a transient improvement in her level of consciousness after intravenous immunoglobulin administration, she did not fully recover. The patient also showed muscle weakness as well as pulmonary impairment that necessitated a tracheotomy. Our case demonstrated the utility of the FilmArray® ME panel as a screening tool for detecting multiple potential pathogens until a specific pathogen could be identified using other diagnostic methods. Clinicians should be aware that EV-A71 CNS infection can occur among adults with severe immunodeficient conditions, and that it leads poor clinical outcomes. Our case suggests that continuous monitoring for this potentially fatal pathogen is warranted for immunocompromised patients.

DOI： 10.1016/j.jiac.2025.102630

Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome 査読国際誌

Kenta Hayashino, Wataru Kitamura, Nobuharu Fujii, Toshiki Terao, Hiroki Kobayashi, Chihiro Kamoi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Yoshinobu Maeda

Cytotherapy 27 ( 4 ) 516 - 521 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

BACKGROUND AIMS: Hypophosphatemia has been recently recognized adverse event in chimeric antigen receptor (CAR)-T cell therapy, complicating 70-75% of patients. Severe hypophosphatemia can cause cytokine release syndrome (CRS)-like symptoms, such as respiratory and cardiovascular dysfunction. Some reports have described the association between inorganic phosphate (iP) and CRS in patients treated with tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel). However, the association between iP and idecabtagene vicleucel (ide-cel) has not been reported and the kinetics of serum iP for each CAR-T cell product have not been compared. We aimed to analyze the kinetics of iP with CAR-T cell products, including ide-cel, and the association between hypophosphatemia and severe CRS. METHODS: We retrospectively analyzed patients aged ≥ 18 years with B-cell malignancies who received CAR-T cell therapy in our institution. All available laboratory data were collected for 21 days after CAR-T cell infusion; clinical and laboratory data were extracted from electronic medical records. RESULTS: A total of 108 patients were treated with CAR-T cell therapy (tisa-cel, n = 56; liso-cel, n = 11; axi-cel, n = 28; ide-cel, n = 13). The cumulative incidence of hypophosphatemia and severe hypophosphatemia were significantly higher in the ide-cel group than the other CAR-T products group (92.3% versus 67.5%, P = 0.0045, and 15.4% versus 2.1%, P = 0.017), Patients treated with ide-cel had significantly lower serum iP levels from day -4 to 8 compared to other CAR-T products. As previous reports, the cumulative incidence of hypophosphatemia in the other CAR-T products group was significantly higher in the severe CRS group than in the mild CRS group (84.0% versus 60.0%, P = 0.0002). In contrast, there was no significant difference between the two groups in the ide-cel group (65% versus 100%, P = 0.13). CONCLUSION: Our results suggest that and that it is important to monitor iP kinetics more carefully because patients treated with ide-cel complicate severe hypophosphatemia, regardless of CRS severity.

DOI： 10.1016/j.jcyt.2024.12.014

Different impacts of granulocyte colony‐stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type 査読国際誌

Takaaki Konuma, Kazuaki Kameda, Kaoru Morita, Tadakazu Kondo, Fumihiko Kimura, Hideki Nakasone, Fumihiko Ouchi, Naoyuki Uchida, Masatsugu Tanaka, Tetsuya Nishida, Takahiro Fukuda, Yuta Hasegawa, Mamiko Sakata‐Yanagimoto, Makoto Onizuka, Masashi Sawa, Shuichi Ota, Noboru Asada, Shin‐Ichiro Fujiwara, Satoshi Yoshihara, Fumihiko Ishimaru, Makoto Yoshimitsu, Yoshinobu Kanda, Marie Ohbiki, Yoshiko Atsuta, Masamitsu Yanada

American Journal of Hematology 100 ( 1 ) 66 - 77 2025年1月

[Treatment outcomes of axicabtagene ciloleucel for relapsed/refractory diffuse large B-cell lymphoma: a retrospective analysis at a single institution]. 査読

Wataru Kitamura, Nobuharu Fujii, Chihiro Kamoi, Toshiki Terao, Akira Yamamoto, Hiroki Kobayashi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Keiko Fujii, Noboru Asada, Daisuke Ennishi, Yoshinobu Maeda

[Rinsho ketsueki] The Japanese journal of clinical hematology 66 ( 2 ) 81 - 91 2025年

記述言語：日本語掲載種別：研究論文（学術雑誌）

The advent of anti-CD19 chimeric antigen receptor-T cell therapy has dramatically changed the treatment strategy for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Three products are recently available in Japan, but to the best of our knowledge, real-world data are only available for tisagenlecleucel. This study was a retrospective analysis of 27 patients who received axicabtagene ciloleucel (axi-cel) for R/R DLBCL at our institution. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 24 (88.9%) and 8 patients (29.6%), respectively, and corticosteroids were used in 19 patients (70.4%). The median follow-up period was 8.1 months (range, 1.0-23.2), and the 6-month progression-free survival and overall survival rates were 80.2% (95% confidence interval [CI], 58.8-91.3) and 92.0% (95%CI, 71.6-97.9), respectively. Although our study was limited by its small sample size and short follow-up period, it demonstrated that axi-cel was highly effective and safe at our institution.

DOI： 10.11406/rinketsu.66.81

Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease. 査読国際誌

Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

Blood 145 ( 8 ) 881 - 896 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in GVHD pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients post-hematopoietic cell transplantation associated with increased chronic GVHD (cGVHD) even in patients receiving post-transplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes (LNs) both pre- and post-transplantation activated antigen-presenting cells (APCs), thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increased in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.

DOI： 10.1182/blood.2024024540

Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors. 査読

Kenta Hayashino, Toshiki Terao, Hisakazu Nishimori, Wataru Kitamura, Hiroki Kobayashi, Chihiro Kamoi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

International journal of hematology 121 ( 2 ) 232 - 243 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS) ≥ 2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p = 0.092) or higher LDH (4.0 vs. 2.0 months, p = 0.018), whereas PFS in the two cellular therapy groups was similar among those with PS ≥ 2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients.

DOI： 10.1007/s12185-024-03888-9

Pericardial artery lymphoma in a patient with dermatomyositis: A case report. 国際誌

Kei Hirose, Takayuki Katsuyama, Natsuki Kubota, Yuya Terajima, Kazuya Matsumoto, Kenta Shidahara, Takato Nakadoi, Shoichi Nawachi, Yu Katayama, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki-Takano, Yoshinori Matsumoto, Noboru Asada, Ken-Ei Sada, Jun Wada

Modern rheumatology case reports 9 ( 1 ) 100 - 103 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

A woman in her 60s presented with erythema on both elbows, dyspnea on exertion, discomfort, and swelling of the left upper extremity, followed by swelling and myalgia of the right upper and lower extremities. She was diagnosed with anti-TIF1γ antibody-positive dermatomyositis with interstitial pneumonia. The initial screening tests for malignant diseases including contrast-enhanced CT, upper and lower endoscopy, and gynecological examination did not reveal any obvious abnormalities. The patient experienced two recurrent episodes of muscle weakness and dysphagia during treatment with intravenous glucocorticoids and cyclophosphamide. Five months after diagnosis, a bone marrow biopsy and positron emission tomography- computed tomography (PET-CT) scan revealed a coronary malignant lymphoma with suspected systemic metastasis. Although chemotherapy was initiated, the patient ultimately succumbed to alveolar hemorrhage. Coronary lymphoma is very rare and there has been no report of a cases associated with myositis. PET-CT may be useful for searching malignancy in anti-TIF1γ antibody-positive dermatomyositis cases of recurrent relapse.

DOI： 10.1093/mrcr/rxae065

Reappraising the prognostic relevance of cytogenetic risk in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. 査読国際誌

Shohei Mizuno, Hiroki Hosoi, Akiyoshi Takami, Takahito Kawata, Noriko Doki, Wataru Takeda, Masatsugu Tanaka, Tetsuya Nishida, Naoyuki Uchida, Yuta Hasegawa, Masashi Sawa, Shuichi Ota, Makoto Onizuka, Hirohisa Nakamae, Noboru Asada, Takahiro Fukuda, Makoto Yoshimitsu, Yoshinobu Kanda, Marie Ohbiki, Yoshiko Atsuta, Takaaki Konuma, Masamitsu Yanada

Annals of hematology 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study aimed to investigate the prognostic relevance of cytogenetic risk in 9826 adults with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) during the first or second complete remission. The 5-year probabilities of overall survival (OS) were 66%, 61%, and 47% (P < 0.001), the cumulative incidences of relapse were 14%, 19%, and 32% (P < 0.001), and the cumulative incidences of non-relapse mortality (NRM) were 23%, 23%, and 25% (P = 0.208) in patients with favorable (n = 1418), intermediate (n = 6747), and poor cytogenetic risk (n = 1661), respectively. The significant effect of cytogenetic risk on OS was strong in all subgroups stratified by age, sex, performance status, disease status, donor type, conditioning intensity, graft-versus-host disease prophylaxis, and transplantation period (P < 0.001 for all). The evaluation of trends in posttransplant outcomes for patients in each cytogenetic risk category indicated that the risk of relapse declined in patients with favorable and intermediate cytogenetics and that the risk of NRM decreased in those with intermediate and poor cytogenetics. Therefore, patients with intermediate cytogenetics experienced the best OS improvement. These results confirm cytogenetic risk as a universal prognostic factor in patients with AML undergoing allogeneic HCT while highlighting the requirement for further improvements in posttransplant OS by reducing NRM in patients with favorable cytogenetics and by reducing relapse in patients with poor cytogenetics.

DOI： 10.1007/s00277-024-06094-z

中枢神経原発リンパ腫におけるplasmablastサブポピュレーションの分子学的特性について

小林宏紀, 千々松良太, 直井友亮, 大谷理浩, 水田亮, 藤井謙太郎, 石田穣治, 村上裕之, 氏家英貴, 池内一廣, 浦田知宏, 清家圭介, 藤原英晃, 淺田騰, 藤井伸治, 松岡賢市, 佐藤康晴, 前田嘉信, 遠西大輔

日本血液学会学術集会 86回 O3 - 2 2024年10月

Simulation-based Bone Marrow Aspiration and Trephine Biopsy Education for Medical Students: A Non-randomized Controlled Trial. 査読

Akira Yamamoto, Hisakazu Nishimori, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Introduction Despite the critical role of bone marrow aspiration and a trephine biopsy (BMAT) in the diagnosis and management of hematological diseases, research on effective teaching methods is limited. Medical students traditionally learn to perform BMAT through observation and replication, which poses a risk to patient safety. Therefore, we developed a novel BMAT simulator for undergraduate medical students using a simulation-based education program. Methods This program, designed for fourth- and fifth-year medical students at Okayama University Medical School, included pre-study materials and one hour of simulation training. Internists practicing hematology served as the controls. Before and after the simulation training, the students completed questionnaires regarding self-confidence, self-evaluation, interest, and knowledge. The procedures were evaluated objectively using a checklist at the end of the program. Results There were significant improvements in self-evaluation, self-confidence, interest, and knowledge acquisition after the simulation program (p≤0.001). The checklist revealed that the mean overall proficiency level of the students was 76.9%, which was significantly higher than that of internists (63.5%) (p≤0.01). Conclusion Our simulation-based education program using the novel BMAT simulator improved medical students' BMAT knowledge and skills.

DOI： 10.2169/internalmedicine.3998-24

Activated CD4<sup>+</sup> T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy 査読

Wataru Kitamura, Noboru Asada, Shuntaro Ikegawa, Hideaki Fujiwara, Chihiro Kamoi, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Yoshinobu Maeda

Internal Medicine 63 ( 13 ) 1863 - 1872 2024年7月

Combination of reduced post‐transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft‐versus‐host disease in human leukocyte antigen‐haploidentical peripheral blood stem‐cell transplantation 査読

Toshiki Terao, Takumi Kondo, Makoto Nakamura, Hiroki Takasuka, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda, Ken‐ichi Matsuoka

eJHaem 2024年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Abstract

We evaluated the clinical impacts of the concurrent modification of post‐transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)‐initiation timing in 61 patients with human leukocyte antigen‐haploidentical transplantation. Reduced‐dose PTCy (80 mg/kg) was associated with a higher incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) than standard‐dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early‐initiation Tac (day ‐1) increased moderate‐to‐severe chronic GVHD than standard‐initiation Tac (day 5) in the reduced‐dose PTCy group (p = 0.032), whereas Tac‐initiation timing did not impact chronic GVHD in the standard‐dose PTCy group. These data indicate that the combination of reduced‐dose PTCy and early‐initiation Tac can amplify chronic GVHD.

DOI： 10.1002/jha2.962

造血幹細胞移植後の難治性腸管合併症に対して腸管切除術を施行した2症例

田中謙太郎, 山本晃, 藤井伸治, 近藤喜太, 田中健大, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 藤井敬子, 松岡賢市, 松川昭博, 吉野正, 前田嘉信

臨床血液 65 ( 5 ) 454 - 454 2024年5月

難治性下腿潰瘍の精査により診断したKlinefelter症候群の1例

川本雅也, 三宅智子, 神野泰輔, 高須賀琴巳, 別木祐介, 松本真理, 澤井希望, 川上佳夫, 森実真, 淺田騰, 戸田洋伸

日本皮膚科学会雑誌 134 ( 6 ) 1711 - 1711 2024年5月

HAVCR2ホモ接合型変異を有し家族内発症した皮下脂肪織炎様T細胞リンパ腫

植田裕子, 藤井伸治, 松原千哲, 近藤歌穂, 寺尾俊紀, 松村彰文, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 藤井敬子, 松岡賢市, 森坂広行, 綾田善行, 吉野正, 前田嘉信

臨床血液 65 ( 5 ) 465 - 466 2024年5月

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma. 査読

Kenta Hayashino, Keisuke Seike, Kanako Fujiwara, Kaho Kondo, Chisato Matsubara, Toshiki Terao, Wataru Kitamura, Chihiro Kamoi, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

International journal of hematology 119 ( 4 ) 459 - 464 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab-Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab-Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

DOI： 10.1007/s12185-024-03711-5

A phase 1/2 study of NS-87/CPX-351 (cytarabine and daunorubicin liposome) in Japanese patients with high-risk acute myeloid leukemia. 査読

Kensuke Usuki, Toshihiro Miyamoto, Takuji Yamauchi, Kiyoshi Ando, Yoshiaki Ogawa, Masahiro Onozawa, Takahiro Yamauchi, Hitoshi Kiyoi, Akira Yokota, Takayuki Ikezoe, Yuna Katsuoka, Satoru Takada, Nobuyuki Aotsuka, Yasuyoshi Morita, Takayuki Ishikawa, Noboru Asada, Shuichi Ota, Atsushi Dohi, Kensaku Morimoto, Shunji Imai, Umi Kishimoto, Koichi Akashi, Yasushi Miyazaki

International journal of hematology 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML. METHODOLOGY: This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60-75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351. RESULTS: In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m2 during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission [CR] or CR with incomplete hematologic recovery [CRi]) was achieved in 60.0% (90% CI: 44.7-74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated. OUTCOMES: NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML.

DOI： 10.1007/s12185-024-03733-z

Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel. 査読国際誌

Wataru Kitamura, Tomohiro Urata, Keiko Fujii, Takuya Fukumi, Kazuhiro Ikeuchi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Transfusion 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

DOI： 10.1111/trf.17765

Clinical significance of gynecological examinations in long-term follow-ups 査読

Chihiro Kamoi, Nobuharu Fujii, Hirofumi Matsuoka, Kanayo Takahashi, Akira Yamamoto, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Japanese Journal of Transplantation and Cellular Therapy 13 ( 2 ) 74 - 80 2024年

Recurrent Cerebral Hemorrhaging with Platelet Dysfunction Accompanied by Anti-glycoprotein VI Autoantibodies in a Patient with TAFRO Syndrome. 査読

Akira Yamamoto, Hisakazu Nishimori, Toshiaki Shirai, Katsuhiro Takano, Aya Komura, Yui Kambara, Takuya Fukumi, Tomohiro Urata, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Kenji Niiya, Katsue Suzuki-Inoue, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 63 ( 13 ) 1917 - 1922 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case of TAFRO syndrome in remission in a patient who experienced recurrent intracranial bleeding despite a normal platelet count and coagulation system. A further investigation suggested the presence of anti-glycoprotein VI (GPVI) autoantibodies in the plasma, which induced platelet dysfunction and bleeding tendency. No new bleeding or relapse of TAFRO syndrome occurred after immunosuppressive therapy was initiated. These findings may help elucidate the autoimmune pathogenesis of TAFRO syndrome.

DOI： 10.2169/internalmedicine.2799-23

[Relapsed primary central nervous system lymphoma treated with CD19 chimeric antigen receptor T-cell therapy and allogeneic hematopoietic stem cell transplantation].

Fuminari Fujii, Toshiki Terao, Hisakazu Nishimori, Kentaro Fujii, Toshihiko Matsuo, Tadashi Yoshino, Hiroko Ueda, Tadashi Oyama, Akifumi Matsumura, Kaho Kondo, Chisato Matsubara, Kanako Fujiwara, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

[Rinsho ketsueki] The Japanese journal of clinical hematology 65 ( 7 ) 622 - 627 2024年

記述言語：日本語掲載種別：研究論文（学術雑誌）

Relapsed and/or refractory (R/R) primary central nervous system lymphoma (PCNSL) has a poor prognosis. A 57-year-old man diagnosed with PCNSL achieved a complete response by high-dose methotrexate-based chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). The disease was not cured, so he was treated with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel after the third relapse. However, the disease relapsed again 28 days after CAR T-cell therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was attempted as curative therapy after bridging with second ASCT and tirabrutinib monotherapy. Although a temporary response was achieved, the disease relapsed 98 days after allo-HSCT. While receiving tirabrutinib for relapse after allo-HSCT, the patient developed acute respiratory failure due to transplant-related toxicity and post-transplant thrombotic microangiopathy. He died 175 days after allo-HSCT. Although various treatments for PCNSL have been investigated in recent years, the treatment strategy for R/R PCNSL has not been established. Further studies are warranted to improve the outcomes of patients with R/R PCNSL.

DOI： 10.11406/rinketsu.65.622

Alpha-Pinene As a Novel Therapeutic Agent for T-Cell Tumors

Masaya Abe, Noboru Asada, Maiko Kimura, Chie Fukui, Daisuke Yamada, Ziyi Wang, Masayuki Miyake, Takeshi Takarada, Mitsuaki Ono, Michinori Aoe, Wataru Kitamura, Masayuki Matsuda, Takashi Moriyama, Akifumi Matsumura, Yoshinobu Maeda

Blood 142 ( Supplement 1 ) 1441 - 1441 2023年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：American Society of Hematology

T-cell acute leukemia and lymphoma have poor prognoses, necessitating the development of novel therapeutic agents. In this study, we investigated the antitumor activity of α-pinene, a monoterpene compound, against T-cell tumors. We evaluated the effects of α-pinene on cell growth inhibition in vitro using the murine T-cell tumor cell line EL-4 and the human-derived T-cell tumor cell line Molt-4. In addition, we assessed the effects of limonene, another monoterpene with reported tumor-suppressive effects, as a comparative agent.

Both α-pinene and limonene demonstrated concentration- and time-dependent inhibition of cell growth in both the EL-4 and Molt-4 cell lines (Figure 1). Moreover, α-pinene exhibited greater potency than limonene in inhibiting the growth of various hematologic malignancies. Importantly, α-pinene and limonene had minimal effects on the growth of normal murine spleen T cells. Further investigation of the mechanisms of action of α-pinene revealed its ability to induce apoptosis and cell cycle arrest in EL-4 and Molt-4 cells. Transcriptomic profiling of α-pinene-treated EL-4 cells using RNA-seq identified differentially expressed genes associated with cellular damage and mitochondrial dysfunction. Increased intracellular ROS levels and mitochondrial impairment were observed in the T-cell tumors treated with α-pinene. The activation of intrinsic apoptotic pathways involving EGR1, p53, BCL-2, and BAX was found to contribute to α-pinene-induced apoptosis in T-cell tumors. Moreover, α-pinene inhibited the NF-κB signaling pathway, resulting in the reduced nuclear translocation of NF-κB p65 and decreased total intracellular NF-κB p65 levels in EL-4 cells. Additionally, we discovered that α-pinene induced ferroptosis, a newly identified programmed cell death process, in EL-4 cells through lipid peroxidation and iron accumulation. Activation of the system x c−/GSH/GPX4 axis and upregulation of iron transporters, such as Slc39a8 and TfR1, were observed in α-pinene-induced ferroptosis. Treatment with the ferroptosis inhibitor Fer-1 partially reversed the tumor-inhibiting effect of α-pinene in EL-4 cells. Finally, we administrated α-pinene to mice subcutaneously injected with luciferase-expressing EL-4 to evaluate the efficacy of α-pinene in vivo. The tumor growth was significantly inhibited by α-pinene treatment (vehicle: 1055 ± 101 mm 3; α-pinene: 701 ± 82 mm 3, p &lt; 0.01, Figure 2) without adverse effects on body weight or behavior. Immunohistochemistry analyses revealed a significant increase of CD8 + T-cells (vehicle: 8.1 ± 2.7 cells / field of view; α-pinene: 43.1 ± 12.2 cells / field of view , p &lt; 0.05) and NK1.1 + cells (vehicle: 5.1 ± 1.0 cells / field of view ; α-pinene: 41.1 ± 9.8 cells / field of view , p &lt; 0.01) in the tumors, suggesting that α-pinene may have an indirect antitumor effect by recruiting immune cells into tumors.

Overall, our findings demonstrate the antitumor activity of α-pinene against T-cell tumors through the induction of apoptosis, cell cycle arrest, and ferroptosis. α-Pinene shows promise as a potential therapeutic agent for T-cell tumors and warrants further investigation for its clinical application.

DOI： 10.1182/blood-2023-181447

CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. 査読国際誌

Naofumi Hara, Eiki Ichihara, Hirohisa Kano, Chihiro Ando, Ayako Morita, Tatsuya Nishi, Sachi Okawa, Takamasa Nakasuka, Atsuko Hirabae, Masaya Abe, Noboru Asada, Kiichiro Ninomiya, Go Makimoto, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

Translational lung cancer research 12 ( 10 ) 2098 - 2112 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. METHODS: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. RESULTS: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. CONCLUSIONS: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.

DOI： 10.21037/tlcr-23-99

Evaluating the efficiency and safety of large-volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study. 査読国際誌

Yuichi Sumii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Transfusion 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS: Although pre-apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/μL, p < .001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL.

DOI： 10.1111/trf.17563

再発・難治性びまん性大細胞型B細胞性リンパ腫に対するtisagenlecleucel輸注後の早期再燃を予測する輸注前因子の検討

北村亘, 藤井伸治, 鴨井千尋, 浦田知宏, 小林宏紀, 山本晃, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 松岡賢市, 前田嘉信

日本造血・免疫細胞療法学会雑誌 12 ( 4 ) 259 - 267 2023年10月

MALTリンパ腫にサルコイドーシス、Sjogren's症候群、肺アミロイドーシスを合併した稀有な症例

阿部将也, 淺田騰, 久保寿夫, 井川卓朗, 植田光晴, 松岡賢市, 前田嘉信

日本血液学会学術集会 85回 991 - 991 2023年10月

Distribution and clinical impact of molecular subtypes with Dark Zone signature of DLBCL in a Japanese real-world study. 査読国際誌

Tomohiro Urata, Yusuke Naoi, Aixiang Jiang, Merrill Boyle, Kazutaka Sunami, Toshi Imai, Yuichiro Nawa, Yasushi Hiramatsu, Kazuhiko Yamamoto, Soichiro Fujii, Isao Yoshida, Tomofumi Yano, Ryota Chijimatsu, Hiroyuki Murakami, Kazuhiro Ikeuchi, Hiroki Kobayashi, Katsuma Tani, Hideki Ujiie, Hirofumi Inoue, Shuta Tomida, Akira Yamamoto, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Keisuke Sawada, Shuji Momose, Jun-Ichi Tamaru, Asami Nishikori, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda, David W Scott, Daisuke Ennishi

Blood advances 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone, that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, that include the dark zone signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a dataset from the cohort of BC Cancer (BCC) (n = 804). Of the 1050 patients where DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to be germinal center B-cell-like (GCB)-DLBCL, activated B-cell-like (ABC)-DLBCL, and DZsigpos-DLBCL, respectively, with the highest prevalence of ABC-DLBCL differing significantly from that of BCC (P < 0.001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with two-year overall survival rates of 88%, 75%, and 66%, respectively (P < 0.0001), with patients of the DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes following rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all P < 0.05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

DOI： 10.1182/bloodadvances.2023010402

Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel. 査読国際誌

Toshiki Terao, Wataru Kitamura, Nobuharu Fujii, Noboru Asada, Chihiro Kamoi, Kanako Fujiwara, Kaho Kondo, Chisato Matsubara, Kenta Hayashino, Keisuke Seike, Hideaki Fujiwara, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Transplantation and cellular therapy 29 ( 9 ) 573.e1-573.e8 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B-cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B-cell lymphoma, follicular lymphoma with histologic transformation to large B-cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.

DOI： 10.1016/j.jtct.2023.06.018

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch 査読

Takumi Kondo, Keiko Fujii, Nobuharu Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 2023年6月

Hematopoietic stem cell–derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide 査読

Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Takuya Fukumi, Miki Iwamoto, Midori Filiz Nishimura, Hiroyuki Sugiura, Yasuhisa Sando, Makoto Nakamura, Yusuke Meguri, Takashi Matsushita, Naoki Tanimine, Maiko Kimura, Noboru Asada, Daisuke Ennishi, Yoshinobu Maeda, Ken-ichi Matsuoka

JCI Insight 8 ( 8 ) 2023年4月

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. 査読国際誌

Noboru Asada, Jun Ando, Satoru Takada, Chikashi Yoshida, Kensuke Usuki, Atsushi Shinagawa, Kenichi Ishizawa, Toshihiro Miyamoto, Hiroatsu Iida, Nobuaki Dobashi, Sumiko Okubo, Hideyuki Honda, Tomomi Soshin, Yasuko Nishimura, Atsuko Tsutsui, Harumi Mukai, Kazuhito Yamamoto

Japanese journal of clinical oncology 2023年4月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In a Phase 3 international clinical trial (VIALE-C), venetoclax plus low-dose cytarabine improved the response rate and overall survival versus placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia who were ineligible for intensive chemotherapy. After the enrollment period of VIALE-C ended, we conducted an expanded access study to provide preapproval access to venetoclax in combination with low-dose cytarabine in Japan. METHODS: Previously, untreated patients with acute myeloid leukemia who were ineligible for intensive chemotherapy were enrolled according to the VIALE-C criteria. Patients received venetoclax (600 mg, Days 1-28, 4-day ramp-up in Cycle 1) in 28-day cycles and low-dose cytarabine (20 mg/m2, Days 1-10). All patients took tumor lysis syndrome prophylactic agents and hydration. Safety endpoints were assessed. RESULTS: Fourteen patients were enrolled in this study. The median age was 77.5 years (range = 61-84), with 78.6% over 75 years old. The most common grade ≥ 3 treatment-emergent adverse event was neutropenia (57.1%). Febrile neutropenia was the most frequent serious adverse event (21.4%). One patient developed treatment-related acute kidney injury, leading to discontinuation of treatment. Two patients died because of cardiac failure and disease progression that were judged not related to study treatment. No patients developed tumor lysis syndrome. CONCLUSIONS: The safety outcomes were similar to those in VIALE-C without new safety signals and were well managed with standard medical care. In clinical practice, more patients with severe background disease are expected, in comparison with in VIALE-C, suggesting that it is important to carefully manage and prevent adverse events.

DOI： 10.1093/jjco/hyad027

A mysterious triangle of blood, bones, and nerves. 査読

Noboru Asada, Yoshio Katayama

Journal of bone and mineral metabolism 2023年2月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The relationship between bone tissue and bone marrow, which is responsible for hematopoiesis, is inseparable. Osteoblasts and osteocytes, which produce and consist of bone tissue, regulate the function of hematopoietic stem cells (HSC), the ancestors of all hematopoietic cells in the bone marrow. The peripheral nervous system finely regulates bone remodeling in bone tissue and modulates HSC function within the bone marrow, either directly or indirectly via modification of the HSC niche function. Peripheral nerve signals also play an important role in the development and progression of malignant tumors (including hematopoietic tumors) and normal tissues, and peripheral nerve control is emerging as a potential new therapeutic target. In this review, we summarize recent findings on the linkage among blood system, bone tissue, and peripheral nerves.

DOI： 10.1007/s00774-023-01402-5

Tfl deletion induces extraordinary Cxcl13 secretion and cachexia in VavP-Bcl2 transgenic mice. 査読国際誌

Kentaro Minagawa, Kanako Wakahashi, Chie Fukui, Yuko Kawano, Hiroki Kawano, Tomohide Suzuki, Shinichi Ishii, Akiko Sada, Shinichiro Nishikawa, Noboru Asada, Yoshio Katayama, Toshimitsu Matsui

Frontiers in immunology 14 1197112 - 1197112 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

Loss of TFL, found in several types of lymphoma, induces excessive CXCL13 secretion through RNA dysregulation contributing to body weight loss and early death in lymphoma model mice. Follicular lymphoma (FL) is associated with overexpressed BCL-2 and other genetic aberrations, including 6q-. We identified a novel gene on 6q25, "Transformed follicular lymphoma (TFL)," from a transformed FL. TFL regulates several cytokines via mRNA degradation, which has been suggested to underlie resolving inflammation. Fluorescence in situ hybridization revealed a deletion of TFL occurred in 13.6% of various B-cell lymphoma samples. We developed VavP-bcl2 transgenic, TFL deficit mice (Bcl2-Tg/Tfl -/-) to seek how TFL affects disease progression in this lymphoma model. While Bcl2-Tg mice developed lymphadenopathy and died around 50 weeks, Bcl2-Tg/Tfl -/- mice lost body weight around 30 weeks and died about 20 weeks earlier than Bcl2-Tg mice. Furthermore, we found a unique B220-IgM+ cell population in the bone marrow of Bcl2-Tg mice. cDNA array in this population revealed that Cxcl13 mRNA in Bcl2-Tg/Tfl -/- mice expressed significantly higher than Bcl2-Tg mice. In addition, bone marrow extracellular fluid and serum showed an extremely high Cxcl13 concentration in Bcl2-Tg/Tfl -/- mice. Among bone marrow cells, the B220-IgM+ fraction was the main producer of Cxcl13 in culture. A reporter assay demonstrated TFL regulates CXCL-13 via induction of 3'UTR mRNA degradation in B lineage cells. These data suggest Tfl regulates Cxcl13 in B220-IgM+ cells in the bone marrow, and a very high concentration of serum Cxcl13 arising from these cells may contribute to early death in lymphoma-bearing mice. Since several reports have suggested the association of CXCL13 expression with lymphoma, these findings provide new insights into cytokine regulation via TFL in lymphoma.

DOI： 10.3389/fimmu.2023.1197112

Early initiation of low-dose gilteritinib maintenance improves posttransplant outcomes in patients with R/R FLT3mut AML. 査読国際誌

Toshiki Terao, Ken-Ichi Matsuoka, Hiroko Ueda, Akifumi Matsumura, Chisato Matsubara, Kaho Kondo, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

Blood advances 7 ( 5 ) 681 - 686 2022年12月

Association between early corticosteroid administration and long-term survival in non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation. 査読

Yui Kambara, Nobuharu Fujii, Yoshiaki Usui, Akira Yamamoto, Hisao Higo, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

International journal of hematology 117 ( 4 ) 578 - 589 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period. Thirty-seven were diagnosed with NIPCs, which consisted of idiopathic pneumonia syndrome, bronchiolitis obliterans, and interstitial lung disease including cryptogenic organizing pneumonia. Among these, 18 died (Dead group) while 19 remained alive (Alive group) during the study period. The median time between NIPC diagnosis and first administration of ≥ 1 mg/kg/day corticosteroids (prednisolone dose equivalent) was significantly longer in the Dead group than the Alive group, at 9 days versus 4 days (p = 0.01). We further divided these cases into those who received prednisolone within seven days and after 8 days. We found that the ≤ 7 days group were more likely to survive after their NIPC diagnosis compared to the ≥ 8 days group (p = 0.06). Our analysis showed that early initiation of corticosteroid therapy is associated with long-term survival in NIPCs.

DOI： 10.1007/s12185-022-03517-3

Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis Through IL-1β Inhibition. 査読国際誌

Junko Itano, Akihiko Taniguchi, Satoru Senoo, Noboru Asada, Yuka Gion, Yuria Egusa, Lili Guo, Naohiro Oda, Kota Araki, Yasuharu Sato, Shinichi Toyooka, Katsuyuki Kiura, Yoshinobu Maeda, Nobuaki Miyahara

American journal of respiratory cell and molecular biology 67 ( 6 ) 654 - 665 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Neuropeptide Y, a 36-amino acid residue polypeptide, distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of neuropeptide Y on pulmonary fibrosis. Neuropeptide Y-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Serum neuropeptide Y levels were also measured in idiopathic pulmonary fibrosis patients and healthy controls. Neuropeptide Y-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1β levels in the lungs compared to wild-type mice. Exogenous neuropeptide Y treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1β levels in the lungs. Moreover, IL-1β neutralization in neuropeptide Y-deficient mice attenuated the fibrotic changes. Neuropeptide Y decreased IL-1β release, and Y1 receptor antagonists inhibited IL-1β release and induced epithelial mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower neuropeptide Y and greater IL-1β levels in the serums compared to healthy controls. Neuropeptide Y expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that neuropeptide Y plays a protective role against pulmonary fibrosis by suppressing IL-1β release and manipulating the neuropeptide Y-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression.

DOI： 10.1165/rcmb.2021-0542OC

Successful haematopoietic progenitor cell collection by plerixafor in combination with reduced dose granulocyte colony-stimulating factor for severe hypoxemia provoked by high-dose granulocyte colony-stimulating factor administration. 査読国際誌

Yui Kambara, Noboru Asada, Kaori Kondo, Yuichi Sumii, Yuki Fujiwara, Keisuke Seike, Yasuhisa Sando, Kyosuke Saeki, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Transfusion medicine (Oxford, England) 2022年9月

末梢神経系による造血調節と腫瘍制御招待査読

淺田騰

臨床血液 63 ( 9 ) 991 - 998 2022年9月

Red blood cell depletion in small‐volume bone marrow processing using manipulation with third‐party red blood cells: A comparison of the performance of the <scp>COBE</scp> spectra and the spectra Optia systems 査読

Yuichi Sumii, Nobuharu Fujii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 2022年8月

Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging 査読

Ruzhica Bogeska, Ana-Matea Mikecin, Paul Kaschutnig, Malak Fawaz, Marleen Büchler-Schäff, Duy Le, Miguel Ganuza, Angelika Vollmer, Stella V. Paffenholz, Noboru Asada, Esther Rodriguez-Correa, Felix Frauhammer, Florian Buettner, Melanie Ball, Julia Knoch, Sina Stäble, Dagmar Walter, Amelie Petri, Martha J. Carreño-Gonzalez, Vinona Wagner, Benedikt Brors, Simon Haas, Daniel B. Lipka, Marieke A.G. Essers, Vivienn Weru, Tim Holland-Letz, Jan-Philipp Mallm, Karsten Rippe, Stephan Krämer, Matthias Schlesner, Shannon McKinney Freeman, Maria Carolina Florian, Katherine Y. King, Paul S. Frenette, Michael A. Rieger, Michael D. Milsom

Cell Stem Cell 29 ( 8 ) 1273 - 1284.e8 2022年8月

Analysis of Immunity against Measles, Mumps, Rubella, and Varicella Zoster in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience 査読

Yoshida S, Fujii N, Kamoi C, Kitamura W, Fujiwara H, Asada N, Nishimori H, Fujii K, Matsuoka KI, Maeda Y

Acta Med Okayama 76 ( 3 ) 247 - 253 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients.

DOI： 10.18926/AMO/63718

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection. 査読国際誌

Shuntaro Ikegawa, Nobuharu Fujii, Keiko Fujii, Maiko Kimura, Masayuki Matsuda, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Yoshinobu Maeda

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 61 ( 6 ) 103453 - 103453 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10-1.59) × 109/kg. The median neutrophil increment one day after GTX was 515 (range, -6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 109/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.

DOI： 10.1016/j.transci.2022.103453

Low hematocrit reduces the efficiency of CD34+ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure. 査読国際誌

Takumi Kondo, Nobuharu Fujii, Keiko Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 62 ( 5 ) 1065 - 1072 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: CD34+ cell collection efficiency (CE) is the determining factor when calculating processed blood volume (PBV) for leukapheresis (LP). However, the factors affecting CE in the continuous mononuclear cell collection (cMNC) protocol performed by the Spectra Optia apheresis system are not well established. STUDY DESIGN AND METHODS: We retrospectively collected the data from 147 consecutive apheresis procedures across 106 healthy donors and 27 patients completed between July 2016 and December 2020 at the Okayama University Hospital. All procedures were performed using the Optia cMNC protocol. RESULTS: The median CD34+ CE2 was significantly higher in the donor samples (64.3%) than in the patient samples (46.8%) (p < .0001). WBC counts, hematocrit, and platelet counts were all significantly higher in the donors than in the patients, and there was a moderate positive correlation between CD34+ CE2 and hematocrit (r = .47, p < .0001), with the equation of the line being y = 1.23x + 12.23. In contrast, there was only a very weak correlation between CD34+ CE2 and WBC or platelet count. In addition, low hematocrit correlated with an increased time to interface formation. CONCLUSION: These data revealed the negative impact of low hematocrit on the efficiency of CD34+ cell collection when using the Optia cMNC protocol and suggest that hematocrit values should also be considered when determining PBV.

DOI： 10.1111/trf.16856

【(新規)抗腫瘍薬〜光と影〜】モガムリズマブ投与後に移植片対宿主病が重症化した成人T細胞白血病の3例

横山恵美, 山崎修, 淺田騰, 吉野正, 森実真

皮膚病診療 44 ( 5 ) 414 - 419 2022年5月

Chronic active Epstein–Barr virus infection presenting as refractory chronic sinusitis 査読

Wataru Kitamura, Hideaki Fujiwara, Akifumi Matsumura, Takaya Higaki, Rei Shibata, Tomohiro Toji, Soichiro Fujii, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

International Journal of Hematology 116 ( 1 ) 139 - 145 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

A 44-year-old Japanese man presented with fever and sore throat. He had a history of refractory chronic sinusitis that did not respond to several years of pharmacotherapy, and underwent endoscopic sinus surgery (ESS) 5 months prior to his presentation, but his symptoms persisted. A biopsy specimen was taken from the right nasal cavity, and extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) was diagnosed. Two years after complete remission was achieved by chemoradiation therapy, he developed hemophagocytic lymphohistiocytosis (HLH) without recurrence of ENKTL. Epstein-Barr virus (EBV)-DNA copy number was relatively high and EBV-infected lymphocytes (CD8 + T cells) were detected in the peripheral blood. Pathological review of the biopsy specimens taken during ESS showed that CD8 + T cells with slightly atypia infiltrating the stroma were EBV positive. These findings suggested that the patient had underlying chronic active EBV infection (CAEBV) that caused the refractory chronic sinusitis, eventually developed into ENKTL, and also caused HLH. Clinicians should consider adult-onset CAEBV in the differential diagnosis of patients with refractory chronic sinusitis.

DOI： 10.1007/s12185-022-03306-y

その他リンク： https://link.springer.com/article/10.1007/s12185-022-03306-y/fulltext.html

Possible prognostic impact of WT1 mRNA expression at day + 30 after haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide for patients with myeloid neoplasm: a multicenter study from the Okayama Hematological Study Group 査読

Wataru Kitamura, Nobuharu Fujii, Yuichiro Nawa, Keigo Fujishita, Hiroyuki Sugiura, Takanori Yoshioka, Yuki Fujiwara, Yoshiaki Usui, Keiko Fujii, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

International Journal of Hematology 115 ( 4 ) 515 - 524 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

BACKGROUND: Previous studies have revealed that relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be predicted by monitoring Wilms' tumor 1 (WT1) mRNA expression. However, only a few studies have investigated patients who received human leukocyte antigen-haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCY-haplo). In this study, we investigated the relationship between WT1 mRNA levels and clinical outcomes in the PTCY-haplo group, and compared them with those in the conventional graft-versus-host disease prophylaxis group (conventional group). METHODS: We retrospectively analyzed 130 patients who received their first allo-HSCT between April 2017 and December 2020, including 26 who received PTCY-haplo. RESULTS: The WT1 mRNA expression level at day + 30 after allo-HSCT associated with increased risk of 1-year cumulative incidence of relapse (CIR) was ≥ 78 copies/μg RNA in the conventional group (p < 0.01) and ≥ 50 copies/μg RNA in the PTCY-haplo group (p = 0.03). CONCLUSIONS: The appropriate cutoff level of WT1 mRNA at day + 30 after allo-HSCT for predicting prognosis in patients treated with PTCY-haplo may be < 50 copies/μg RNA.

DOI： 10.1007/s12185-022-03290-3

その他リンク： https://link.springer.com/article/10.1007/s12185-022-03290-3/fulltext.html

Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia. 査読国際誌

Hiroyuki Murakami, Ken-Ichi Matsuoka, Takeru Asano, Takashi Moriyama, Akifumi Matsumura, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Tomohiro Toji, Tadashi Yoshino, Yoshinobu Maeda

Case reports in oncology 15 ( 3 ) 974 - 979 2022年

記述言語：英語

Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment.

DOI： 10.1159/000526697

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy 査読国際誌

Kazuhito Yamamoto, Atsushi Shinagawa, Courtney D DiNardo, Keith W Pratz, Kenichi Ishizawa, Toshihiro Miyamoto, Norio Komatsu, Yasuhiro Nakashima, Chikashi Yoshida, Noriko Fukuhara, Kensuke Usuki, Takahiro Yamauchi, Noboru Asada, Norio Asou, Ilseung Choi, Yasushi Miyazaki, Hideyuki Honda, Sumiko Okubo, Misaki Kurokawa, Ying Zhou, Jiuhong Zha, Jalaja Potluri, Itaru Matsumura

Japanese Journal of Clinical Oncology 52 ( 1 ) 29 - 38 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Background</title>
The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

</sec>
<sec>
<title>Methods</title>
Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1–7 of each 28-day cycle.

</sec>
<sec>
<title>Results</title>
Median follow-up was 16.3 months (range, 1.0–20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation.

</sec>
<sec>
<title>Conclusions</title>
This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.

</sec>

DOI： 10.1093/jjco/hyab170

Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature 査読

Wataru Kitamura, Noboru Asada, Tetsuya Tabata, Rei Shibata, Tatsuya Nishi, Yuka Kato, Hiroki Takasuka, Hideaki Fujiwara, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-ichi Matsuoka, Katsuyuki Kiura, Tadashi Yoshino, Yoshinobu Maeda

Journal of Clinical and Experimental Hematopathology 62 ( 1 ) 35 - 40 2021年11月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Society for Lymphoreticular Tissue Research

Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL.

DOI： 10.3960/jslrt.21010

Transformation to diffuse large B-cell lymphoma with germinal center B-cell like subtype and discordant light chain expression in a patient with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. 査読

Hiroki Kobayashi, Noboru Asada, Yuria Egusa, Tomoka Ikeda, Misa Sakamoto, Masaya Abe, Daisuke Ennishi, Masahiro Sakata, Akinobu Takaki, Soichiro Kawahara, Yusuke Meguri, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda

International journal of hematology 114 ( 3 ) 401 - 407 2021年9月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare indolent B-cell neoplasm, and a gain-of-function mutation in the myeloid differentiation primary response 88 (MYD88), L265P, is a commonly recurring mutation in patients with WM/LPL. Histological transformation of WM/LPL to an aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL) is rare, and transformed DLBCL has a worse prognosis than de novo DLBCL, partly because transformed DLBCL is mostly classified as non-germinal center B-cell-like (non-GCB) subtype. We herein describe a 75-year-old man with DLBCL with a history of WM/LPL. DLBCL in this patient showed the GCB subtype, and the light chain restriction of DLBCL was different from that of the antecedent WM/LPL, indicating that the two types of lymphoma cells had distinctive origins. However, DLBCL in this patient harbored the MYD88 L265P mutation, and polymerase chain reaction and Sanger sequencing of the DLBCL and WM/LPL for immunoglobulin heavy chain gene rearrangement suggested a clonal relationship between the two lymphomas. Since the outcome of transformed DLBCL is worse than for de novo DLBCL, it is important to evaluate the clonal relationship between primary WM/LPL and the corresponding transformed DLBCL, even if the DLBCL expresses a GCB subtype or discordant light chain restriction.

DOI： 10.1007/s12185-021-03157-z

Reduced dose of PTCy followed by adjuvant α-galactosylceramide enhances GVL effect without sacrificing GVHD suppression. 査読国際誌

Makoto Nakamura, Yusuke Meguri, Shuntaro Ikegawa, Takumi Kondo, Yuichi Sumii, Takuya Fukumi, Miki Iwamoto, Yasuhisa Sando, Hiroyuki Sugiura, Noboru Asada, Daisuke Ennishi, Shuta Tomida, Emi Fukuda-Kawaguchi, Yasuyuki Ishii, Yoshinobu Maeda, Ken-Ichi Matsuoka

Scientific reports 11 ( 1 ) 13125 - 13125 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by α-galactosylceramide (α-GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of α-GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4+Foxp3+ regulatory T cells. These studies indicate that α-GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.

DOI： 10.1038/s41598-021-92526-z

Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis. 査読

Masaaki Nishinohara, Hisakazu Nishimori, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

Acta medica Okayama 75 ( 3 ) 279 - 287 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD.

DOI： 10.18926/AMO/62219

Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea during Treatment: A Case Report and Literature Review. 査読

Wataru Kitamura, Daisuke Ennishi, Ryoya Yukawa, Ryo Sasaki, Chikamasa Yoshida, Hiroki Takasuka, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Koji Abe, Tadashi Yoshino, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 60 ( 19 ) 3155 - 3160 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients.

DOI： 10.2169/internalmedicine.7180-21

Laparoscopic Hepatectomy for the Patient with Hemophilia A with High Titer Factor VIII Inhibitor. 査読

Tatsuo Matsuda, Yuzo Umeda, Kazuhiro Yoshida, Tadakazu Matsuda, Masatoshi Uno, Masaya Abe, Noboru Asada, Yoshinobu Maeda, Takahito Yagi, Toshiyoshi Fujiwara

Acta medica Okayama 75 ( 2 ) 199 - 204 2021年4月

記述言語：英語

We present the first case of laparoscopic left lateral segmentectomy for hepatocellular carcinoma (HCC) in a patient with hemophilia A, acquired hepatitis C, and high-titer factor VIII inhibitor, which was confirmed by preoperative diagnosis. He underwent laparoscopic left lateral segmentectomy with the administration of recombinant activated factor VII. Surgery could be performed with reduced intraoperative hemorrhage. He experienced postoperative intra-abdominal wall hemorrhage, which was successfully managed with red cell concentrates transfusion and administration of recombinant activated factor VII. Laparoscopic hepatectomy can be applied for hemophilia patients with high titer inhibitors.

DOI： 10.18926/AMO/61901

FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization. 査読国際誌

Shinichi Ishii, Tomohide Suzuki, Kanako Wakahashi, Noboru Asada, Yuko Kawano, Hiroki Kawano, Akiko Sada, Kentaro Minagawa, Yukio Nakamura, Seiya Mizuno, Satoru Takahashi, Toshimitsu Matsui, Yoshio Katayama

Blood 137 ( 11 ) 1457 - 1467 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Fibroblast growth factor 23 (FGF-23) hormone is produced by bone-embedded osteocytes and regulates phosphate homeostasis in kidneys. We found that administration of granulocyte colony-stimulating factor (G-CSF) to mice induced a rapid, substantial increase in FGF-23 messenger RNA in bone marrow (BM) cells. This increase originated mainly from CD45-Ter119+CD71+ erythroblasts. FGF-23 protein in BM extracellular fluid was markedly increased during G-CSF-induced hematopoietic progenitor cell (HPC) mobilization, but remained stable in the blood, with no change in the phosphate level. Consistent with the BM hypoxia induced by G-CSF, low oxygen concentration induced FGF-23 release from human erythroblast HUDEP-2 cells in vitro. The efficient mobilization induced by G-CSF decreased drastically in both FGF-23-/- and chimeric mice with FGF-23 deficiency, only in hematopoietic cells, but increased in osteocyte-specific FGF-23-/- mice. This finding suggests that erythroblast-derived, but not bone-derived, FGF-23 is needed to release HPCs from BM into the circulation. Mechanistically, FGF-23 did not influence CXCL-12 binding to CXCR-4 on progenitors but interfered with their transwell migration toward CXCL-12, which was canceled by FGF receptor inhibitors. These results suggest that BM erythroblasts facilitate G-CSF-induced HPC mobilization via FGF-23 production as an intrinsic suppressor of chemoattraction.

DOI： 10.1182/blood.2020007172

Author Correction: 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy. 国際誌

Yasuhisa Sando, Ken-Ichi Matsuoka, Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Hiroyuki Sugiura, Makoto Nakamura, Miki Iwamoto, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Atae Utsunomiya, Takashi Oka, Yoshinobu Maeda

Scientific reports 11 ( 1 ) 6420 - 6420 2021年3月

Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab. 国際誌

Shuntaro Ikegawa, Yusuke Meguri, Kentaro Mizuhara, Takuya Fukumi, Hiroki Kobayashi, Yuichi Sumii, Takumi Kondo, Yasuhisa Sando, Miki Iwamoto, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yuka Fujisawa, Toshi Imai, Yoshinobu Maeda, Ken-Ichi Matsuoka

Leukemia 35 ( 3 ) 929 - 931 2021年3月

Histologic Transformation from Follicular Lymphoma to Diffuse Large B-cell Lymphoma Detected during Colonoscopy. 査読

Masaya Iwamuro, Yasushi Yamasaki, Takehiro Tanaka, Noboru Asada, Ken-Ichi Matsuoka, Sakiko Hiraoka, Yoshiro Kawahara, Hiroyuki Okada

Acta medica Okayama 75 ( 5 ) 625 - 629 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

A 77-year-old Japanese woman who had been treated for follicular lymphoma for 8 years developed abdominal pain and intra-abdominal lymphadenopathies. Colonoscopy revealed an elevated lesion in the rectum, which presented as two humps with erosions. A diagnosis of histologic transformation of follicular lymphoma to diffuse large B-cell lymphoma was made by endoscopic biopsy. This case underscores the importance of endoscopy examinations and biopsy of newly emerged gastrointestinal lesions for the prompt diagnosis of histologic transformation, since salvage chemotherapy must be initiated quickly in such cases.

DOI： 10.18926/AMO/62775

Total body irradiation-based haploidentical hematopoietic stem cell transplantation using posttransplant cyclophosphamide after administration of inotuzumab ozogamicin: A case report. 査読国際誌

Masaya Abe, Nobuharu Fujii, Kentaro Mizuhara, Tomohiro Urata, Yuichi Sumii, Yuki Fujiwara, Keisuke Seike, Yasuhisa Sando, Makoto Nakamura, Keiko Fujii, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Yoshinobu Maeda

Leukemia research reports 15 100241 - 100241 2021年

記述言語：英語

Owing to the poor prognosis of relapsed or refractory acute lymphoblastic leukemia (ALL), hematopoietic stem cell transplantation (HSCT) followed by effective salvage therapy is required. Inotuzumab ozogamicin (INO) was developed for ALL refractory to standard chemotherapy. However, previous reports suggest that sinusoidal obstruction syndrome (SOS) risk increases in patients with HSCT receiving INO, especially with dual alkylating agents. We report a case of relapsed Philadelphia chromosome-negative B-ALL where the patient underwent haploidentical HSCT using fludarabine/total body irradiation conditioning and posttransplant cyclophosphamide. Successful engraftment was achieved without SOS development.

DOI： 10.1016/j.lrr.2021.100241

5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy 査読国際誌

Yasuhisa Sando, Ken-ichi Matsuoka, Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Hiroyuki Sugiura, Makoto Nakamura, Miki Iwamoto, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Atae Utsunomiya, Takashi Oka, Yoshinobu Maeda

Scientific Reports 10 ( 1 ) 17237 - 17237 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

<title>Abstract</title>
Photodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies.

DOI： 10.1038/s41598-020-74174-x

その他リンク： http://www.nature.com/articles/s41598-020-74174-x

Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease 査読国際誌

Miki Iwamoto, Shuntaro Ikegawa, Takumi Kondo, Yusuke Meguri, Makoto Nakamura, Yasuhisa Sando, Hiroyuki Sugiura, Yuichi Sumii, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Misako Shibakura, Yoshinobu Maeda, Ken-ichi Matsuoka

Bone Marrow Transplantation 56 ( 4 ) 956 - 959 2020年10月

Persistent hypogammaglobulinemia due to immunoglobulin class switch impairment by peri-transplant rituximab therapy 査読

Kentaro Mizuhara, Nobuharu Fujii, Yusuke Meguri, Takahide Takahashi, Michinori Aoe, Makoto Nakamura, Keisuke Seike, Yasuhisa Sando, Keiko Fujii, Masaya Abe, Yuichi Sumii, Tomohiro Urata, Yuki Fujiwara, Kyosuke Saeki, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

International Journal of Hematology 112 ( 3 ) 422 - 426 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications of allogeneic hematopoietic stem cell transplantation (HSCT). Rituximab is effective for PTLD; however, rituximab can produce adverse effects, including hypogammaglobulinemia. Here, we present the case of an 18-year-old female with refractory cytopenia of childhood who developed persistent selective hypogammaglobulinemia with low immunoglobulin G (IgG) 2 and IgG4 levels and monoclonal protein after rituximab therapy against probable PTLD. Despite B-cell recovery, the serum IgG levels gradually declined, reaching < 300 mg/dL at 33 months after rituximab treatment. In addition, class-switched memory (CD27 + IgD -) B cells were limited in phenotypic analysis. These findings suggest that peri-HSCT rituximab may contribute to an abnormal B-cell repertoire induced by impaired immunoglobulin class switch.

DOI： 10.1007/s12185-020-02886-x

その他リンク： http://link.springer.com/article/10.1007/s12185-020-02886-x/fulltext.html

Allogeneic hematopoietic stem cell transplantation in a prior lung transplant recipient 査読

Yuki Fujiwara, Ken-ichi Matsuoka, Miki Iwamoto, Yuichi Sumii, Masaya Abe, Kentaro Mizuhara, Tomohiro Urata, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Junichi Sugita, Hajime Kobayashi, Takahiro Oto, Yoshinobu Maeda

International Journal of Hematology 112 ( 6 ) 871 - 877 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Hematological diseases after solid organ transplant (SOT) are an emerging issue as the number of long-term SOT survivors increases. Expertise in managing patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) after SOT from independent donors is needed; however, clinical reports of HSCT after SOT are limited, and the feasibility and risk are not well understood. In particular, HSCT in prior lung transplant recipients is thought to be complicated as the lung is immunologically distinct and is constantly exposed to the surrounding environment. Herein, we describe a case of successful HSCT in a patient with myelodysplastic syndromes who had previously received a lung transplant from a deceased donor for bronchiolitis obliterans syndrome. Reports about cases of HSCT after lung transplant are quite rare; thus, we discuss the mechanisms of immune tolerance through the clinical course of our case. This case suggests that HSCT after SOT can be considered a therapeutic option in cases where the transplanted organ is functionally retained and the hematological disease is in remission.

DOI： 10.1007/s12185-020-02967-x

その他リンク： http://link.springer.com/article/10.1007/s12185-020-02967-x/fulltext.html

原発性マクログロブリン血症から形質転換したGerminal Center B-cellタイプのびまん性大細胞型B細胞リンパ腫の症例

小林宏紀, 淺田騰, 遠西大輔, 阿部将也, 池田知佳, 坂本美彩, 江草侑厘安, 廻勇輔, 西森久和, 藤井伸治, 松岡賢市, 佐藤康晴, 吉野正, 前田嘉信

日本リンパ網内系学会会誌 60 82 - 82 2020年7月

Intestinal Diffuse Large B-Cell Lymphoma in a Patient with Systemic Lupus Erythematosus 査読国際誌

Masaya Iwamuro, Takahide Takahashi, Yoko Ota, Takehiro Tanaka, Noboru Asada, Shuya Yano, Mayu Uka, Rei Nakamura, Yuki Baba, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Okada

Case Reports in Gastrointestinal Medicine 2020 1 - 5 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Hindawi Limited

A 44-year-old Japanese woman with systemic lupus erythematosus (SLE) presented to our hospital with abdominal pain. Radiological and endoscopic examinations led to the diagnosis of diffuse large B-cell lymphoma of the jejunum, which was subsequently resected. Patients with SLE reportedly have an increased risk of non-Hodgkin lymphoma, as demonstrated by our patient. Hence, lymphoma should be considered in the differential diagnosis of neoplastic lesions emerging in SLE patients. In addition, flow cytometry using endoscopically biopsied fragments is useful for the immediate diagnosis of lymphoma, leading to timely and accurate preoperative staging.

DOI： 10.1155/2020/7947540

その他リンク： http://downloads.hindawi.com/journals/crigm/2020/7947540.xml

Efficacy of HLA virtual cross‐matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation 査読国際誌

Keisuke Seike, Nobuharu Fujii, Naomi Asano, Shigenori Ohkuma, Yasushi Hirata, Keiko Fujii, Yasuhisa Sando, Makoto Nakamura, Kazunori Naito, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Kazuo Tsubaki, Fumio Otsuka, Yoshinobu Maeda

Transfusion 60 ( 3 ) 473 - 478 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

BACKGROUND: Cross-matched platelet (cross-matched PLT) transfusion is effective for immune-mediated platelet transfusion refractoriness (PTR), but is more costly and time-consuming for physical cross-match than using standard PLT units. Recent studies have reported the utility of human leucocyte antigens (HLA) virtual cross-matched PLT (HLA-matched PLT) that is defined as HLA-A/B matched or no antibody against donor-specific antigen. Here, we evaluated the effect of HLA-matched PLTs for PTR in post hematopoietic stem cell transplant (HSCT) recipients. STUDY DESIGN AND METHODS: Our study included a total of 241 PLTs in 16 patients who underwent HSCT at Okayama University Hospital between 2010 and 2017, receiving either HLA-matched or cross-matched PLTs. We calculated the 24-hour corrected count increments (CCI-24) to evaluate the effect of PLTs. A CCI-24 ≥ 4500 was considered to be a successful transfusion. RESULTS: We analyzed 139 cross-matched PLTs and 102 HLA-matched PLTs. In the immune-mediated PTR, the rate of successful transfusion was 60.5% for cross-matched PLT and 63.4% for HLA-matched PLT (p = 0.825). On the other hand, the median CCI-24 for cross-matched PLT transfusions and HLA-matched PLT transfusions were 1856 and 5824 (p < 0.001), with a success rate of 28.1 and 54.1% in cases with non-immune-mediated PTR, respectively (p = 0.001). CONCLUSION: The effectiveness of HLA-matched PLT is not inferior to cross-matched PLT. This result indicates that physical cross-match can be omitted in post HSCT PTR.

DOI： 10.1111/trf.15664

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/trf.15664

Author Correction: Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche (Nature Medicine, (2018), 24, 6, (782-791), 10.1038/s41591-018-0030-x)

Maria Maryanovich, Ali H. Zahalka, Halley Pierce, Sandra Pinho, Fumio Nakahara, Noboru Asada, Qiaozhi Wei, Xizhe Wang, Paul Ciero, Jianing Xu, Avigdor Leftin, Paul S. Frenette

Nature Medicine 25 ( 4 ) 701 2019年4月

Salvage Haploidentical Transplantation Using Low-dose ATG for Early Disease Relapse after First Allogeneic Transplantation: A Retrospective Single-center Review. 査読

Okamoto S, Matsuoka KI, Sakamoto M, Usui Y, Fujiwara Y, Kondo T, Tani K, Saeki K, Meguri Y, Asada N, Ennishi D, Nishimori H, Fujii K, Fujii N, Maeda Y

Acta medica Okayama 73 ( 2 ) 161 - 171 2019年4月

Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis. 査読国際誌

Wakahashi K, Minagawa K, Kawano Y, Kawano H, Suzuki T, Ishii S, Sada A, Asada N, Sato M, Kato S, Shide K, Shimoda K, Matsui T, Katayama Y

Blood 133 ( 15 ) 1619 - 1629 2019年2月

A case report of TAFRO syndrome successfully treated by immunosuppressive therapies with plasma exchange. 査読

Meguri Y, Asada N, Nakasako Y, Kondo E, Kambara Y, Yamamoto A, Masunari T, Sezaki N, Ikeda G, Toji T, Yoshino T, Kiguchi T

Annals of hematology 98 ( 2 ) 537 - 539 2018年7月

Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL 査読

Kentaro Minagawa, Kanako Wakahashi, Hiroki Kawano, Shinichiro Nishikawa, Chie Fukui, Yuko Kawano, Noboru Asada, Mari Sato, Akiko Sada, Yoshio Katayama, Toshimitsu Matsui

JOURNAL OF IMMUNOLOGY 192 ( 4 ) 1512 - 1524 2014年2月

新しい全自動型血液成分分離装置Spectra Optiaを用いた末梢血幹細胞採取Cobe Spectraと比較して

藤井敬子, 淺田騰, 西森久和, 山川美和, 森繰代, 狩山由貴, 池田亮, 浅野尚美, 小郷博昭, 藤井伸治, 岩月啓氏

日本輸血細胞治療学会誌 59 ( 1 ) 91 - 91 2013年2月

Delayed neutrophil engraftment in cord blood transplantation with intensive administration of mycophenolate mofetil for GVHD prophylaxis 査読

A. Okamura, M. Shimoyama, S. Ishii, K. Wakahashi, N. Asada, H. Kawano, Y. Kawamori, S. Nishikawa, K. Minagawa, Y. Katayama, T. Matsui

BONE MARROW TRANSPLANTATION 46 ( 1 ) 148 - 149 2011年1月

A clinicopathological study of 13 cases of intravascular lymphoma: experience in a single institution over a 9-yr period 査読

Kosei Matsue, Noboru Asada, Masami Takeuchi, Masayuki Yamakura, Shun-Ichi Kimura, Jun Odawara, Takatoshi Aoki

EUROPEAN JOURNAL OF HAEMATOLOGY 80 ( 3 ) 236 - 244 2008年3月

IgD-λ型のM蛋白血症を呈した原発性アミロイドーシス

木村俊一, 岩塚良太, 青木孝友, 小田原淳, 淺田騰, 山倉昌之, 竹内正美, 末永孝生

臨床血液 = The Japanese Journal of Clinical Hematology 48 ( 12 ) 1555 - 1558 2007年12月

[Primary amyloidosis associated with IgD-lambda M-proteinemia]. 査読

Kimura S, Iwatsuka R, Aoki T, Odawara J, Asada N, Yamakura M, Takeuchi M, Matsue K

[Rinsho ketsueki] The Japanese journal of clinical hematology 48 ( 12 ) 1555 - 1558 2007年12月

Successful combined use of tranexamic acid and unfractionated heparin for life-threatening bleeding associated with intravascular coagulation in a patient with chronic myelogenous leukemia in blast crisis 査読

Mihoko Koseki, Noboru Asada, Hidetaka Uryu, Masami Takeuchi, Hidesaku Asakura, Kosei Matsue

INTERNATIONAL JOURNAL OF HEMATOLOGY 86 ( 5 ) 403 - 406 2007年12月

Intravascular Large B cell Lymphoma(IVL)におけるPET/CTの有用性

小田原淳, 淺田騰, 青木孝友, 木村俊一, 山倉昌之, 竹内正美, 末永孝生

臨床血液 48 ( 9 ) 982 2007年9月

悪性リンパ腫における組織学的骨髄浸潤とFDG‐PET/CTの相関:組織型による感度の違い

山倉昌之, 小田原淳, 青木孝友, 木村俊一, 淺田騰, 竹内正美, 末永孝生

臨床血液 48 ( 9 ) 992 2007年9月

当院における50歳以上の同種造血幹細胞移植の検討

青木孝友, 高梨葉子, 小田原淳, 淺田騰, 木村俊一, 山倉昌之, 竹内正美, 末永孝生

臨床血液 48 ( 9 ) 1104 2007年9月

血管内悪性リンパ腫の診断におけるランダム皮膚生検の有用性

淺田騰, 小田原淳, 青木孝友, 木村俊一, 山倉昌之, 竹内正美, 末永孝生

臨床血液 48 ( 9 ) 982 2007年9月

Identification of cardiac metastasis of primary gastric diffuse large B-cell lymphoma 査読

Masaharu Tsubokura, Noboru Asada, Jun Odawara, Takatoshi Aoki, Masayuki Yamakura, Masami Takeuchi, Kosei Matsue

British Journal of Haematology 137 ( 3 ) 179 2007年5月

18F-fluorodeoxyglucose positron emission tomography for evaluation of intravascular large B-cell lymphoma 査読

Jun Odawara, Noboru Asada, Takatoshi Aoki, Masayuki Yamakura, Masami Takeuchi, Toshihiro Ohuchi, Kosei Matsue

British Journal of Haematology 136 ( 5 ) 684 2007年3月

Rapid improvement of hypoxemia by the use of rituximab in patients with pulmonary intravascular lymphoma 査読

Kosei Matsue, Masami Takeuchi, Hidetaka Uryu, Mihoko Koseki, Noboru Asada, Yosinori Kaneko

LEUKEMIA & LYMPHOMA 48 ( 1 ) 197 - 200 2007年1月

Picture in Clinical Hematology

淺田騰, 松岡賢市, 小田原淳, 青木孝友, 山倉昌之, 竹内正美, 末永孝生

臨床血液 48 ( 1 ) 1 - 1 2007年

当院におけるカンジダ血症についての検討

木村俊一, 淺田騰, 瓜生英尚, 末永考生, 岩渕千太郎, 土井朝子, 細川直登, 岩田健太郎

感染症学雑誌 80 ( 6 ) 783 2006年11月

[Analysis of serum Aspergillus galactomannan contents conducted at our hospital during the past 2 years]. 査読

Uryu H, Kozeki M, Asada N, Takeuchi M, Suenaga T

The Japanese journal of antibiotics 59 ( 5 ) 413 - 414 2006年10月

Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin 査読

K Matsue, H Uryu, M Koseki, N Asada, M Takeuchi

CLINICAL INFECTIOUS DISEASES 42 ( 6 ) 753 - 757 2006年3月

Gastrointestinal stromal tumor(GIST)を合併した膿胸関連リンパ腫(PAL)の1例

浅田騰, 根本仁, 森康雄, 新谷大悟, 竹内正美, 末永孝生

臨床血液 45 ( 1 ) 84 - 85 2004年1月

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