{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:55:15Z","timestamp":1791320115247,"version":"4.3.1"},"reference-count":35,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"unspecified","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Key projects of the National Natural Science Foundation of China","award":["81730008"],"award-info":[{"award-number":["81730008"]}]},{"name":"Key projects of the National Natural Science Foundation of China","award":["82130003"],"award-info":[{"award-number":["82130003"]}]},{"DOI":"10.13039\/100022963","name":"key R & D Program of Zhejiang Province","doi-asserted-by":"crossref","award":["2018C03016-2"],"award-info":[{"award-number":["2018C03016-2"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100022963","name":"key R & D Program of Zhejiang Province","doi-asserted-by":"crossref","award":["2019C03016"],"award-info":[{"award-number":["2019C03016"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"crossref"}]},{"name":"General Project of the National Natural Science Foundation of China","award":["81870153"],"award-info":[{"award-number":["81870153"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,1,17]]},"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Murine chimeric antigen receptor T (CAR-T) cell therapy has demonstrated clinical benefit in patients with relapsed\/refractory (R\/R) B-cell acute lymphoblastic leukemia (B-ALL). However, the potential immunogenicity of the murine single-chain variable fragment domain may limit the persistence of CAR-T cell, leading to relapse.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a clinical trial to determine the safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell (hCART19) for R\/R B-ALL. Fifty-eight patients (aged 13\u201374 years) were enrolled and treated between February 2020 and March 2022. The endpoints were complete remission (CR) rate, overall survival (OS), event-free survival (EFS), and safety.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, 93.1% (54\/58) of patients achieved CR or CR with incomplete count recovery (CRi) by day 28, with 53 patients having minimal residual disease negativity. With a median follow-up of 13.5 months, the estimated 1-year OS and EFS were 73.6% (95% CI 62.1% to 87.4%) and 46.0% (95% CI 33.7% to 62.8%), with a median OS and EFS of 21.5 months and 9.5 months, respectively. No significant increase in human antimouse antibodies was observed following infusion (p=0.78). Duration of B-cell aplasia in the blood was observed for as long as 616 days, which was longer than that in our prior mCART19 trial. All toxicities were reversible, including severe cytokine release syndrome, which developed in 36% (21\/58) of patients and severe neurotoxicity, which developed in 5% (3\/58) of patients. Compared with our prior mCART19 trial, patients treated with hCART19 had longer EFS without increased toxicity. Additionally, our data also suggest that patients treated with consolidation therapy, including allogeneic hematopoietic stem cell transplantation or CD22-targeted CAR-T cell, following hCART19 therapy had a longer EFS than those without consolidation therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>hCART19 has good short-term efficacy and manageable toxicity in R\/R B-ALL patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04532268\">NCT04532268<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-005701","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T09:40:12Z","timestamp":1676886012000},"page":"e005701","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell therapy for patients with relapsed\/refractory B-ALL"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04532268","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1123-9407","authenticated-orcid":false,"given":"Fengmei","family":"Song","sequence":"first","affiliation":[{"name":"Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of 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Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of HematologyZhejiang University, Hangzhou, China"},{"name":"Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of HematologyZhejiang University, Hangzhou, China"},{"name":"Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Wu","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of HematologyZhejiang University, Hangzhou, China"},{"name":"Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simao","family":"Huang","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of HematologyZhejiang University, Hangzhou, China"},{"name":"Zhejiang Province Engineering Laboratory for Stem 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ShanghaiChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2723-1621","authenticated-orcid":false,"given":"He","family":"Huang","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of HematologyZhejiang University, Hangzhou, China"},{"name":"Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Wei","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China"},{"name":"Institute of HematologyZhejiang 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