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Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia

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机构: [1]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China; [2]Innovat Cellular Therapeut Co Ltd, SiDanSai Biotechnol Co Ltd, Shanghai, Peoples R China; [3]Capital Med Univ, Beijing Tiantan Hosp, Dept Hematol, Beijing, Peoples R China; [4]Zhejiang Univ, Dept Blood Transfus, Affiliated Hosp 1, Sch Med, Hangzhou, Zhejiang, Peoples R China; [5]Zhejiang Prov Peoples Hosp, Clin Res Ctr, Hangzhou, Zhejiang, Peoples R China; [6]Zhejiang Univ, Inst Hematol, Sch Med, Hangzhou, Zhejiang, Peoples R China; [7]Innovat Cellular Therapeut Co Ltd, Room 201,Bldg 4,998 Halei Rd, Shanghai 201203, Peoples R China
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Purpose: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor-modified T cells against CD19 (CART19) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. Experimental Design: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine-and cyclophosphamide-based lymphodepletion. The postinfusion responses, toxicities, expansion, and persistence of CART19s in enrolled patients were observed and monitored. Results: We enrolled 15 patients with R/R ALL. The median transduction efficiency of CART19s was 33%. In vitro cytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 x 10(6)/kg to 9.8 x 10(6)/kg. Twelve patients achieved complete remission 1 month after CART19s infusion. CART19s expanded and persisted in peripheral blood and bone marrow. At 150 days, the overall survival rate and leukemia-free survival rate were 65.5% and 37.8%, respectively. The cumulative incidence of relapse and the nonrelapse mortality rate were 54.5% and 7.7%, respectively. Four patients underwent subsequent haploidentical hematopoietic stem cell transplantation. In this trial, 10 patients experienced cytokine release syndrome (CRS). Grade 3 CRS developed in 40% of patients and was associated with a higher disease burden on day -1 and a higher number of previous relapses. Conclusions: This trial demonstrated potent antileukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation. (C) 2016 AACR.

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出版当年[2016]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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出版当年[2015]版:
Q1 ONCOLOGY
最新[2023]版:
Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China;
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通讯机构: [1]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China; [2]Innovat Cellular Therapeut Co Ltd, SiDanSai Biotechnol Co Ltd, Shanghai, Peoples R China; [7]Innovat Cellular Therapeut Co Ltd, Room 201,Bldg 4,998 Halei Rd, Shanghai 201203, Peoples R China
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