CAR-T细胞治疗复发/难治性急性淋巴细胞白血病的临床观察——附3例报告

Clinical study on the chimeric antigen receptor T cells in the treatment of relapsed/refractory acute lymphoblast leukemia

目的探索嵌合抗原受体T细胞(CAR-T细胞)治疗复发/难治性急性B淋巴细胞白血病的效果。方法回顾性分析本院2015年4月-2016年1月3例复发/难治性急性B淋巴细胞白血病患者采用CAR-T细胞治疗的临床疗效。3例患者均为多次诱导化疗不能达到完全缓解,或复发后再次诱导治疗无效。均采集自体外周血T淋巴细胞进行转染、培养。回输前以氟达拉滨+环磷酰胺方案预处理,回输CAR-T细胞数量为0.97至1.0×106/kg。结果2例患者在CAR-T细胞输注后1月内达到完全缓解,1例患者无效。达到缓解的2例患者在CAR-T细胞治疗后的第3和第6个月复发。复发后的1例患者出现CD19阴性克隆复发;在整个治疗过程中,未发生严重的不良反应。结论 CAR-T细胞是治疗复发/难治CD19抗原阳性急性淋巴细胞白血病的有效方法,能够降低耐药患者体内肿瘤负荷,甚至达到完全缓解,但短期内复发较高且复发的白血病细胞可能出现CD19抗原缺失。因此,在临床的应用方法还需要进行临床研究,也可作为异基因造血干细胞移植前的桥接治疗。

Objective To explore the effect of chimeric antigen receptor T cells （ CART cells ） on the treatment of relapsed/refractory acute lymphoblast leukemia （ALL）. Methods Three cases with relapsed/refractory ALL received treatment of CART cells were enrolled in this study from April 2015 to January 2016. None of the patients reached complete remission （CR） through several cycles of induce chemotherapy or induce chemotherapy after relapse. The CART cells were made with the collected peripheral T cells from the patients themselves. The fludara and cyclophosphamide were used as conditioning regimen before the infusion of CART cells. The numbers of CART cells ranged from 0. 97 × 10^6 to 1.0 ×10^6 per kg. Results Two patients reached CR during 1 month after the infusion of CART cells, one patient experienced failure. The two patients reached CR relapse again after treatment of CART ceils at the third month and the sixth month, respectively. Inter- estingly, one relapsed patient lost the expression of CD19 antigen. No serious complications were observed during the treat- me,at of CART cells. Conclusion It is an effective way to treat the relapsed/refractory ALL with CART ceils. The CR rate is high, but most of the cases relapsed in a very short time, accompanied by the loss of CD19 antigen. Further study should be carried out and the treatment of CART cells could be used as a bridge before HSCT.