{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:55:03Z","timestamp":1791320103350,"version":"4.3.1"},"reference-count":13,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2021-I2M-1-041"],"award-info":[{"award-number":["2021-I2M-1-041"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2021-I2M-C&T-B-079"],"award-info":[{"award-number":["2021-I2M-C&T-B-079"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2022-I2M-1-022"],"award-info":[{"award-number":["2022-I2M-1-022"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81920108006"],"award-info":[{"award-number":["81920108006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270218"],"award-info":[{"award-number":["82270218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300238"],"award-info":[{"award-number":["82300238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20291"],"award-info":[{"award-number":["U22A20291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,11,8]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>B-cell maturation antigen(BCMA)-directed chimeric antigen receptor (CAR)-T-cell therapy has significantly improved the treatment of relapsed or refractory multiple myeloma (MM). Nevertheless, the uncommon phenomenon of biphasic CAR-T cell expansion in vivo and its related severe toxicities have not been methodically described and studied. Herein, we report a case of patients with MM who experienced two CAR-T cell expansion peaks and subsequently developed multiple severe toxicities following BCMA CAR-T cell infusion. The first expansion peak occurred on Day 7, accompanied by grade 3 cytokine release syndrome. The second peak occurred on Day 28, associated with severe immune effector cell-associated hematotoxicity (ICAHT), immune effector-cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), and polymicrobial infections. Both ICAHT and IEC-HS were refractory to our standard treatments; however, human umbilical cord mesenchymal stem cell infusion exhibited some efficacy in improving cytopenia. Despite the administration of a broad-spectrum anti-infective regimen, cytomegalovirus viremia remained uncontrollable, resulting in the development of central nervous system infection, neurological symptoms, and ultimately death. Additionally, we also employed high-dimensional 33-color spectral flow cytometry to describe the dynamic changes in immune cell components and functions between the two expansion peaks. Collectively, this case provides novel insights into the biphasic CAR-T expansion and related immune effector cell-associated toxicities.<\/jats:p>","DOI":"10.1136\/jitc-2024-010080","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T04:21:30Z","timestamp":1732767690000},"page":"e010080","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Uncommon biphasic CAR-T expansion induces hemophagocytic lymphohistiocytosis-like syndrome and fatal multiple infections following BCMA CAR-T cell therapy: a case report"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-7810","authenticated-orcid":false,"given":"Wenqiang","family":"Yan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology for Esophageal Mediastinal and Lymphatic tumors, Zhongnan Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaishuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Sui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigang","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-4913","authenticated-orcid":false,"given":"Dehui","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of 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Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma. 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