{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:31:35Z","timestamp":1793039495286,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    For successful chimeric antigen receptor T (CAR\u2010T) cell therapy, CAR\u2010T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR\u2010T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B\u2010cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) was significantly higher, and their platelet counts (12.0 vs. 17.0\u2009\u00d7\u200910\n                    <jats:sup>4<\/jats:sup>\n                    \/\u03bcL;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01) and CD4\/CD8 T\u2010cell ratio (0.30 vs. 0.56;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.013 for \u22656\u2009cycles with washout period of 3\u201324\u2009months; OR, 57.09;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005 for \u22653\u2009cycles with washout period of &lt;3\u2009months), low platelet counts (OR, 0.495 per 10\n                    <jats:sup>5<\/jats:sup>\n                    \/\u03bcL;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.022) or low CD4\/CD8 ratios (&lt;one third) (OR, 3.249;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR\u2010T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk\u2010adapted strategies may help to optimize CAR\u2010T cell therapy for DLBCL patients.\n                  <\/jats:p>","DOI":"10.1111\/bjh.18831","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T08:45:47Z","timestamp":1682412347000},"page":"256-266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Risk factors for\n                    <scp>CAR\u2010T<\/scp>\n                    cell manufacturing failure among\n                    <scp>DLBCL<\/scp>\n                    patients: A nationwide survey in Japan"],"prefix":"10.1111","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9381-0421","authenticated-orcid":false,"given":"Tomoyasu","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine and Center for Research and Application of Cellular Therapy Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Hematology and Oncology Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8537-2422","authenticated-orcid":false,"given":"Satoshi","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy Hyogo Medical University Hospital  Nishinomiya Japan"},{"name":"Department of Hematology Hyogo Medical University Hospital  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Division of Transfusion and Cell Therapy Tokyo Metropolitan Komagome Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Fujii","sequence":"additional","affiliation":[{"name":"Division of Transfusion Okayama University Hospital  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Henzan","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Medicine Kyushu University Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Kahata","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University, Faculty of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Center for Transfusion Medicine and Cell Therapy Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Hematopoietic Stem Cell Transplantation National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Umezawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8003-2584","authenticated-orcid":false,"given":"Kentaro","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ashida","sequence":"additional","affiliation":[{"name":"Division of Hematology and Rheumatology, Department of Internal Medicine Kindai University Hospital  Osakasayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minami","family":"Yamada\u2010Fujiwara","sequence":"additional","affiliation":[{"name":"Division of Blood Transfusion and Cell Therapy Tohoku University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Hanajiri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Yonetani","sequence":"additional","affiliation":[{"name":"Department of Hematology Kobe City Medical Center General Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Hematology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-7902","authenticated-orcid":false,"given":"Yuji","family":"Shimura","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion University Hospital, Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Nishikii","sequence":"additional","affiliation":[{"name":"Department of Hematology University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0392-9221","authenticated-orcid":false,"given":"Norio","family":"Shiba","sequence":"additional","affiliation":[{"name":"Department of Division of Blood Transfusion and Cell Therapy Yokohama City University  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-9428","authenticated-orcid":false,"given":"Naoya","family":"Mimura","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy Chiba University Hospital  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Cell Therapy and Transfusion Medicine Juntendo University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology Kurashiki Central Hospital  Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Hematology Osaka Metropolitan University Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Ikemoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Hyogo Medical University Hospital  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Iwaki","sequence":"additional","affiliation":[{"name":"Division of Blood Transfusion and Cell Therapy Tohoku University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4523-2994","authenticated-orcid":false,"given":"Shin\u2010ichiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Division of Cell Transplantation and Transfusion Jichi Medical University Hospital  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9617-486X","authenticated-orcid":false,"given":"Masaki","family":"Ri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokiko","family":"Nagamura\u2010Inoue","sequence":"additional","affiliation":[{"name":"Department of Cell Processing and Transfusion, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Tanosaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University, Faculty of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9662-5093","authenticated-orcid":false,"given":"Yasuyuki","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine and Center for Research and Application of Cellular Therapy Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Hematology and Oncology Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707447"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804980"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708566"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14110"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.08.015"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2403"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2022.05.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.11.018"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354194"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02153"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007057"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad5222"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-552174"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00648"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0010-1"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000600"},{"issue":"8","key":"e_1_2_10_18_1","first-page":"832","article-title":"Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high\u2010dose therapy and infectious complications","volume":"85","author":"Steingrimsdottir H","year":"2000","journal-title":"Haematologica"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215276"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.247"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85309"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2797"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15722"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4545-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.699128"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00172"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.1.1996.5.213"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.18831","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T20:06:32Z","timestamp":1699992392000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.18831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/bjh.18831"],"URL":"https:\/\/doi.org\/10.1111\/bjh.18831","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,25]]},"assertion":[{"value":"2023-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}