Faculty Profiles - ENNISHI Daisuke

Papers - ENNISHI Daisuke

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Chronological improvement in precision oncology implementation in Japan

Kuniko Sunami, Yoichi Naito, Keigo Komine, Toraji Amano, Daisuke Ennishi, Mitsuho Imai, Hidenori Kage, Masashi Kanai, Hirotsugu Kenmotsu, Takafumi Koyama, Takahiro Maeda, Sachi Morita, Daisuke Sakai, Shinji Kohsaka, Katsuya Tsuchihara, Yusuke Saigusa, Takayuki Yoshino

Cancer Science 2022.9

骨・軟部腫瘍の基礎科学のトピックスクリニカルシークエンスによる肉腫のゲノム医療

中田英二, 藤原智洋, 国定俊之, 二川摩周, 遠西大輔, 久保寿夫, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1533 - S1533 2022.9

Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma. International journal

Ryota Chijimatsu, Shogo Kobayashi, Yu Takeda, Masatoshi Kitakaze, Shotaro Tatekawa, Yasuko Arao, Mika Nakayama, Naohiro Tachibana, Taku Saito, Daisuke Ennishi, Shuta Tomida, Kazuki Sasaki, Daisaku Yamada, Yoshito Tomimaru, Hidenori Takahashi, Daisuke Okuzaki, Daisuke Motooka, Takahito Ohshiro, Masateru Taniguchi, Yutaka Suzuki, Kazuhiko Ogawa, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hideshi Ishii

iScience 25 ( 8 ) 104659 - 104659 2022.8

Language：English Publishing type：Research paper (scientific journal)

Single-cell RNA sequencing (scRNAseq) has been used to assess the intra-tumor heterogeneity and microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, previous knowledge is not fully universalized. Here, we built a single cell atlas of PDAC from six datasets containing over 70 samples and >130,000 cells, and demonstrated its application to the reanalysis of the previous bulk transcriptomic cohorts and inferring cell-cell communications. The cell decomposition of bulk transcriptomics using scRNAseq data showed the cellular heterogeneity of PDAC; moreover, high levels of tumor cells and fibroblasts were indicative of poor-prognosis. Refined tumor subtypes signature indicated the tumor cell dynamics in intra-tumor and their specific regulatory network. We further identified functionally distinct tumor clusters that had close interaction with fibroblast subtypes via different signaling pathways dependent on subtypes. Our analysis provided a reference dataset for PDAC and showed its utility in research on the microenvironment of intra-tumor heterogeneity.

DOI： 10.1016/j.isci.2022.104659

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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

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 2022.8

Tumor-associated antigen PRAME exhibits dualistic functions that are targetable in diffuse large B cell lymphoma. International journal

Katsuyoshi Takata, Lauren C Chong, Daisuke Ennishi, Tomohiro Aoki, Michael Yu Li, Avinash Thakur, Shannon Healy, Elena Viganò, Tao Dao, Daniel Kwon, Gerben Duns, Julie S Nielsen, Susana Ben-Neriah, Ethan Tse, Stacy S Hung, Merrill Boyle, Sung Soo Mun, Christopher M Bourne, Bruce Woolcock, Adèle Telenius, Makoto Kishida, Shinya Rai, Allen W Zhang, Ali Bashashati, Saeed Saberi, Gianluca D'Antonio, Brad H Nelson, Sohrab P Shah, Pamela A Hoodless, Ari M Melnick, Randy D Gascoyne, Joseph M Connors, David A Scheinberg, Wendy Béguelin, David W Scott, Christian Steidl

The Journal of clinical investigation 132 ( 10 ) 2022.5

Language：English Publishing type：Research paper (scientific journal)

PRAME is a prominent member of the cancer testis antigen family of proteins, which triggers autologous T cell-mediated immune responses. Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME downmodulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL. In turn, PRC2-regulated genes were repressed in isogenic PRAME-KO lymphoma cell lines, and PRAME was found to directly interact with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects, leading to PRAME expression and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis and provide a preclinical rationale for synergistic therapies combining epigenetic reprogramming with PRAME-targeted therapies.

DOI： 10.1172/JCI145343

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Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection

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 103453 - 103453 2022.5

Low hematocrit reduces the efficiency of <scp>CD34</scp> ⁺ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure

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 2022.3

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

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 2022.2

Response to entrectinib in a malignant glioneuronal tumor with ARHGEF2-NTRK fusion

Kazuhiko Kurozumi, Kentaro Fujii, Kana Washio, Joji Ishida, Yoshihiro Otani, Tamotsu Sudo, Makoto Tahara, Koichi Ichimura, Daisuke Ennishi, Isao Date

Neuro-Oncology Advances 4 ( 1 ) 2022.1

Publishing type：Research paper (scientific journal)

Glioneuronal tumor (GNT) is a rare tumor. We previously reported a case of high-grade GNT with Rho/Rac guanine nucleotide factor 2 (ARHGEF2)-neurotrophic tropomyosin receptor kinase (NTRK)1 fusion and emphasized the importance of complementary molecular analysis.1 MRI at follow-up showed tumor progression. A cancer gene panel test was performed, and the presence of the ARHGEF2-NTRK1 fusion gene was confirmed. Treatment with entrectinib, an inhibitor of NTRK, was started. MRI follow-ups revealed dramatic responses. However, the patient reported severe general fatigue, and the dose was decreased following the reduced drug protocol. This case highlights the necessity of determining an optimal dose and further profiling the side effects of NTRK inhibitors.

DOI： 10.1093/noajnl/vdac094

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

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

Language：English

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

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Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands

Nobushige Tsuboi, Joji Ishida, Yosuke Shimazu, Hisanori Edaki, Atsuhito Uneda, Yoshihiro Otani, Kentaro Fujii, Kazuhiko Kurozumi, Daisuke Ennishi, Hiroyuki Yanai, Isao Date

Acta Medica Okayama 76 ( 4 ) 473 - 477 2022

Publishing type：Research paper (scientific journal)

Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.

DOI： 10.18926/AMO/63907

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Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report. International journal

Mashu Futagawa, Hideki Yamamoto, Mariko Kochi, Yusaku Urakawa, Reimi Sogawa, Fumino Kato, Mika Okazawa-Sakai, Daisuke Ennishi, Katsunori Shinozaki, Hirofumi Inoue, Hiroyuki Yanai, Akira Hirasawa

Hereditary cancer in clinical practice 19 ( 1 ) 48 - 48 2021.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. CASE PRESENTATION: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. CONCLUSIONS: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.

DOI： 10.1186/s13053-021-00205-x

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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.

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 2021.9

Language：English Publishing type：Research paper (scientific journal)

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

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Secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs: A case report. International journal

Kohei Taniguchi, Hiroyuki Yanai, Tatsuya Kaji, Toshio Kubo, Daisuke Ennishi, Akira Hirasawa, Tadashi Yoshino

Journal of cutaneous pathology 48 ( 8 ) 1069 - 1074 2021.8

Language：English

Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.

DOI： 10.1111/cup.14028

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Characterization of DLBCL with a PMBL gene expression signature. International journal

Gerben Duns, Elena Viganò, Daisuke Ennishi, Clementine Sarkozy, Stacy S Hung, Elizabeth Chavez, Katsuyoshi Takata, Christopher Rushton, Aixiang Jiang, Susana Ben-Neriah, Bruce W Woolcock, Graham W Slack, Eric D Hsi, Jeffrey W Craig, Laura K Hilton, Sohrab P Shah, Pedro Farinha, Anja Mottok, Randy D Gascoyne, Ryan D Morin, Kerry J Savage, David W Scott, Christian Steidl

Blood 138 ( 2 ) 136 - 148 2021.7

Language：English Publishing type：Research paper (scientific journal)

Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typically affects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas with gene expression features of PMBL have been described in nonmediastinal sites, raising questions about how these tumors should be classified. Here, we investigated whether these nonmediastinal lymphomas are indeed PMBLs or instead represent a distinct group within diffuse large B-cell lymphoma (DLBCL). From a cohort of 325 de novo DLBCL cases, we identified tumors from patients without evidence of anterior mediastinal involvement that expressed a PMBL expression signature (nm-PMBLsig+; n = 16; 5%). A majority of these tumors expressed MAL and CD23, proteins typically observed in bona fide PMBL (bf-PMBL). Evaluation of clinical features of nm-PMBLsig+ cases revealed close associations with DLBCL, and a majority displayed a germinal center B cell-like cell of origin (GCB). In contrast to patients with bf-PMBL, patients with nm-PMBLsig+ presented at an older age and did not show pleural disease, and bone/bone marrow involvement was observed in 3 cases. However, although clinically distinct from bf-PMBL, nm-PMBLsig+ tumors resembled bf-PMBL at the molecular level, with upregulation of immune response, JAK-STAT, and NF-κB signatures. Mutational analysis revealed frequent somatic gene mutations in SOCS1, IL4R, ITPKB, and STAT6, as well as CD83 and BIRC3, with the latter genes significantly more frequently affected than in GCB DLBCL or bf-PMBL. Our data establish nm-PMBLsig+ lymphomas as a group within DLBCL with distinct phenotypic and genetic features. These findings may have implications for gene expression- and mutation-based subtyping of aggressive B-cell lymphomas and related targeted therapies.

DOI： 10.1182/blood.2020007683

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Reduced dose of PTCy followed by adjuvant α-galactosylceramide enhances GVL effect without sacrificing GVHD suppression. International journal

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 2021.6

Language：English Publishing type：Research paper (scientific journal)

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

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A Case of Metastatic Fumarate Hydratase-Deficient-like Renal Cell Carcinoma Successfully Managed by Ipilimumab plus Nivolumab.

Takanori Sekito, Atsushi Takamoto, Yasuyuki Kobayashi, Masao Mitsui, Shogo Watari, Risa Kubota, Takuya Sadahira, Takehiro Iwata, Shingo Nishimura, Kohei Edamura, Tomoko Sako, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Rei Shibata, Daisuke Ennishi, Yasutomo Nasu

Acta medica Okayama 75 ( 3 ) 397 - 402 2021.6

Language：English Publishing type：Research paper (scientific journal)

We report a 62-year-old male with metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) without fumarate hydratase (FH) mutation (FH-deficient-like RCC). The International Metastatic RCC Database Consortium risk score was intermediate, and immunotherapy with nivolumab and ipilimumab (Ipi/ Nivo) was initiated. Four cycles of Ipi/Nivo and 5 cycles of nivolumab resulted in a complete response of the metastases. Hypophysitis occurred as an immune-related adverse event after four cycles of Ipi/Nivo. The prognosis of patients with FH-deficient RCC is generally poor. Few reports of FH-deficient RCC successfully treated with Ipi/Nivo have been published. Ipi/Nivo can be effective for treating FH-deficient RCC.

DOI： 10.18926/AMO/62237

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

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 2021.6

Language：English Publishing type：Research paper (scientific journal)

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

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Safety and antitumor activity of acalabrutinib for relapsed/refractory B-cell malignancies: A Japanese phase I study. International journal

Koji Izutsu, Kiyoshi Ando, Daisuke Ennishi, Hirohiko Shibayama, Junji Suzumiya, Kazuhito Yamamoto, Satoshi Ichikawa, Koji Kato, Kyoya Kumagai, Priti Patel, Sakura Iizumi, Nobuya Hayashi, Hisashi Kawasumi, Kosho Murayama, Hirokazu Nagai

Cancer science 112 ( 6 ) 2405 - 2415 2021.6

Language：English Publishing type：Research paper (scientific journal)

This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.

DOI： 10.1111/cas.14886

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Molecular attributes underlying central nervous system and systemic relapse in diffuse large B-cell lymphoma. International journal

Keren Isaev, Daisuke Ennishi, Laura Hilton, Brian Skinnider, Karen L Mungall, Andrew J Mungall, Mehran Bakhtiari, Rosemarie Tremblay-LeMay, Anjali Silva, Susana Ben-Neriah, Merrill Boyle, Diego Villa, Marco A Marra, Christian Steidl, Randy D Gascoyne, Ryan Morin, Kerry J Savage, David W Scott, Robert Kridel

Haematologica 106 ( 5 ) 1466 - 1471 2021.5

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Papers - ENNISHI Daisuke