研究者詳細 - 遠西　大輔

論文 - 遠西　大輔

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Correction to: The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan.

Kuniko Sunami, Yoichi Naito, Eriko Aimono, Toraji Amano, Daisuke Ennishi, Hidenori Kage, Masashi Kanai, Keigo Komine, Takafumi Koyama, Takahiro Maeda, Sachi Morita, Daisuke Sakai, Shinji Kohsaka, Katsuya Tsuchihara, Takayuki Yoshino

International journal of clinical oncology 26 ( 5 ) 1007 - 1007 2021年5月

The impact of MYC and BCL2 structural variants in tumors of DLBCL morphology and mechanisms of false-negative MYC IHC. 国際誌

Brett Collinge, Susana Ben-Neriah, Lauren Chong, Merrill Boyle, Aixiang Jiang, Tomoko Miyata-Takata, Pedro Farinha, Jeffrey W Craig, Graham W Slack, Daisuke Ennishi, Anja Mottok, Barbara Meissner, Elizabeth A Chavez, Alina S Gerrie, Diego Villa, Ciara Freeman, Kerry J Savage, Laurie H Sehn, Ryan D Morin, Andrew J Mungall, Randy D Gascoyne, Marco A Marra, Joseph M Connors, Christian Steidl, David W Scott

Blood 137 ( 16 ) 2196 - 2208 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

When the World Health Organization defined high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) as a clinical category, rearrangements were the only structural variant (SV) incorporated. An "atypical double-hit" category has been proposed, encompassing tumors with concurrent MYC and BCL2 SVs other than cooccurring translocations (ie, copy number variations [CNVs]). Although the identification of a gene expression signature (DHITsig) shared among tumors harboring MYC and BCL2 rearrangements (HGBL-DH/TH-BCL2) has confirmed a common underlying biology, the biological implication of MYC and BCL2 CNVs requires further elucidation. We performed a comprehensive analysis of MYC and BCL2 SVs, as determined by fluorescent in situ hybridization (FISH), in a cohort of 802 de novo tumors with diffuse large B-cell lymphoma morphology. Although BCL2 CNVs were associated with increased expression, MYC CNVs were not. Furthermore, MYC and BCL2 CNVs, in the context of atypical double-hit, did not confer a similar gene expression profile as HGBL-DH/TH-BCL2. Finally, although MYC immunohistochemistry (IHC) has been proposed as a screening tool for FISH testing, 2 mechanisms were observed that uncoupled MYC rearrangement from IHC positivity: (1) low MYC messenger RNA expression; and (2) false-negative IHC staining mediated by a single-nucleotide polymorphism resulting in an asparagine-to-serine substitution at the 11th amino acid residue of MYC (MYC-N11S). Taken together, these results support the current exclusion of MYC and BCL2 CNVs from HGBL-DH/TH and highlight the ability of a molecular-based classification system to identify tumors with shared biology that FISH and IHC fail to fully capture.

DOI： 10.1182/blood.2020007193

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

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

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Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease. 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 2021年4月

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

The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan.

International journal of clinical oncology 26 ( 3 ) 443 - 449 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Since June 2019, cancer genomic profiling (CGP) tests have been reimbursed by the National Health Insurance system in Japan, with restrictions for government-designated hospitals with a molecular tumor board composed of multidisciplinary specialists, known as an expert panel (EP). The standardization of EPs is a critical challenge for implementing precision oncology in the clinical setting. METHODS: Data on consecutive cases who underwent the CGP tests at 11 core hospitals between June 2019 and January 2020 were collected. We evaluated the proportions of cases that received genomically matched treatments, including investigational new drugs (INDs) based on CGP results, and/or for which genetic counseling was recommended. Two simulated cases were annotated by each EP. The annotated reports were then centrally assessed. RESULTS: Each EP mainly discussed the applicability to genomically matched treatments and the necessity of performing genetic counseling. A pre-review of the report by key members in each EP reportedly made the EP conference more interactive and efficient, and thereby saved time. A total of 747 cases underwent CGP tests, 28 cases (3.7%) received genomically matched treatment, and 17 cases (2.3%) were referred for genetic counseling. Annotated reports for the simulated cases varied across the EPs, particularly the number of recommended IND trials, which seemed to be associated with the actual number of participants in IND trials. CONCLUSIONS: This investigation provides reference data for the application of precision oncology in a clinical setting. Further investigations on the standardization of clinical annotations are warranted.

DOI： 10.1007/s10147-020-01844-1

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Follow-up with serum IgG4-monitoring in 8 patients with IgG4-related disease diagnosed by a lacrimal gland mass.

Toshihiko Matsuo, Takehiro Tanaka, Yasuharu Sato, Hitomi Kataoka, Mayu Uka, Daisuke Ennishi, Tomofumi Yano

Journal of clinical and experimental hematopathology : JCEH 61 ( 1 ) 10 - 21 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

DOI： 10.3960/jslrt.20048

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Aggressive B-cell lymphoma(DLBCL, HGBCL)のゲノム異常による病型分類

遠西大輔

臨床血液 62 ( 5 ) 418 - 423 2021年

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

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DLBCLとhigh-grade B-cell lymphomaの分子病態に関わる最近の知見

遠西大輔

臨床血液 62 ( 6 ) 624 - 630 2021年

記述言語：日本語出版者・発行元：一般社団法人日本血液学会

悪性リンパ腫の中でも最も患者数の多いびまん性大細胞型リンパ腫（diffuse large B-cell lymphoma, DLBCL）は，臨床的，生物学的に非常に不均一な疾患単位であり，様々な分子遺伝学的異常が腫瘍形成に関わっていると考えられる。これまで，特に細胞起源に関わる遺伝子発現プロファイルや免疫微小環境の特徴，遺伝子解析技術の進歩による新規遺伝子異常の発見により，分子病態の解明と細分類化が進んでいる。このような分子学的特徴は臨床予後とも関連性が示され，DLBCLの個別化医療を考える上で非常に重要な因子である。本稿ではDLBCLの分子病態の最新の知見を紹介しながら，個別化医療の可能性についても述べていく。

DOI： 10.11406/rinketsu.62.624

その他リンク： https://search.jamas.or.jp/link/ui/2021315726

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

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 2021年

Four Cases of Desquamative Esophagitis Occurring after Hematopoietic Stem Cell Transplantation.

Masaya Iwamuro, Daisuke Ennishi, Ken-Ichi Matsuoka, Takehiro Tanaka, Shotaro Okanoue, Yuka Obayashi, Hiroyuki Sakae, Yoshiro Kawahara, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 59 ( 23 ) 3015 - 3022 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

We herein report four patients with desquamative esophagitis that developed one to nine days after peripheral blood stem cell transplantation (PBSCT). Three patients underwent allogeneic PBSCT for leukemia, and the other underwent autologous PBSCT for pineoblastoma. Esophagogastroduodenoscopy revealed mucosal sloughing and fresh blood in the esophagus. Fasting and intravenous proton pump inhibitor therapy in addition to blood transfusion improved the esophageal lesions within five to seven days in three patients. These cases indicate that desquamative esophagitis can occur in patients who receive hematopoietic stem cell transplantation. Although blood transfusions may be required, it can be resolved within seven days.

DOI： 10.2169/internalmedicine.4977-20

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

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12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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 (Tokyo, Japan) 59 ( 21 ) 2757 - 2761 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation (vol 60, pg 473, 2020)

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

TRANSFUSION 60 ( 11 ) 2765 - 2765 2020年11月

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

Scientific reports 10 ( 1 ) 17237 - 17237 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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Toward a New Molecular Taxonomy of Diffuse Large B-cell Lymphoma. 国際誌

Daisuke Ennishi, Eric D Hsi, Christian Steidl, David W Scott

Cancer discovery 10 ( 9 ) 1267 - 1281 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Diffuse large B-cell lymphoma (DLBCL) represents a grouping of clinically and biologically heterogeneous tumors. Application of advanced molecular technology has significantly expanded our knowledge of DLBCL pathobiology, allowing identification of subgroups with common, potentially targetable, biological themes. Here, we review the recent molecular analyses that could provide a paradigm shift to a new taxonomy, foundational to the rational transition to precision medicine. We discuss how classification systems may be synthesized into a common taxonomy, drawing strength from the relationships between genetic alterations, gene expression, and tumor microenvironment. Finally, challenges to translating such a taxonomy to the clinic will be outlined.

DOI： 10.1158/2159-8290.CD-20-0174

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

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）

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

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