Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia
Potent Anti-leukemia Activities of Chimeric Antigen Receptor-Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia
复制标题
嵌合抗原受体修饰的 T 细胞针对 CD19 对中国复发/难治性急性淋巴细胞白血病患者具有有效的抗白血病活性。
DOI：
10.1158/1078-0432.ccr-16-1799
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发表时间：
2017-07-01
影响因子：
11.5
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Hu, Yongxian;Wu, Zhao;Huang, He
目的：复发/难治性急性淋巴细胞白血病（R/R ALL）患者预后较差。嵌合抗原受体修饰的T细胞抗CD19 （CART19）显示出抗白血病的活性。然而，中国患者的系统试验数据有限。实验设计：用cd19导向的CAR慢病毒载体转导的T细胞输注在氟达拉滨和环磷酰胺为基础的淋巴细胞清除的R/R ALL患者中。观察和监测入组患者中cart19的输注后反应、毒性、扩张和持久性。结果：我们纳入了15例R/R ALL患者。cart19的中位转导效率为33%。体外细胞毒性实验表明，cart19具有显著的抗白血病活性。患者接受剂量为1.1 × 10(6)/kg至9.8 × 10(6)/kg的cart19输注。12例患者在输注cart19后1个月达到完全缓解。cart19在外周血和骨髓中扩展并持续存在。150 d时，总生存率和无白血病生存率分别为65.5%和37.8%。累计复发率为54.5%，未复发死亡率为7.7%。4例患者随后接受了单倍体造血干细胞移植。在本试验中，10例患者出现细胞因子释放综合征（CRS）。40%的患者发生3级CRS，并且与第1天较高的疾病负担和较高的既往复发次数相关。结论：该试验表明，cart19对中国R/R ALL患者具有有效的抗白血病活性。疾病复发仍然是主要障碍。然而，cart19术后复发风险高的患者可能受益于随后的单倍同型造血干细胞移植。(c) 2016年aacr。
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.