Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation
Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation
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DOI：
10.1111/bjh.14923
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发表时间：
2017-11-01
影响因子：
6.5
通讯作者：
Huang, Xiaojun
中科院分区：
文献类型：
--
作者：
Chen, Yuhong;Cheng, Yifei;Huang, Xiaojun
B细胞急性淋巴细胞白血病(B-ALL)半相合造血干细胞移植(Haplo-HSCT)失败的常见原因是复发，HSCT后供者淋巴细胞输注无反应者预后很差。尽管供者来源的CD19导向的嵌合抗原受体修饰(CAR)T细胞可以潜在地治疗白血病，但其有效性和安全性在单核-造血干细胞移植后复发的B-ALL病例中尚未得到证实。在2015年1月至2017年1月期间，两名和四名患者分别接受了一次和两次单核细胞造血干细胞移植捐赠者的CAR T细胞输注。5例(83.33%)获得微小残留病(MRD)阴性缓解；1例患者在发展成严重的血栓性微血管病变后自动出院而不进行评估。5名有反应的患者中有4名在2-7个月后复发，1名在第二次输液后MRD阴性缓解后死于脓毒症。其他第二次输液接受者中没有一人获得第二次完全缓解。5名患者(83.33%)经历了8个疗程的1-3级细胞因子释放综合征；2名患者接受了tocilizumab治疗。2例(33.3%)和1例患者分别发展为2级和3级急性移植物抗宿主病(AGVHD)；前者经糖皮质激素控制。供者来源的CAR T细胞输注似乎对HAPLO-HSCT后复发的B-ALL是有效和安全的，尽管需要更大的临床研究。
Relapse is a common cause of failure in patients with B-cell acute lymphoblastic leukaemia (B-ALL) after haploidentical haematopoietic stem cell transplantation (haplo-HSCT), and non-responders to donor lymphoblastic infusion after HSCT have a very poor prognosis. Although donor-derived CD19-directed chimeric antigen receptor-modified (CAR) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B-ALL cases after haplo-HSCT. Between January 2015 and January 2017, two and four patients each received one and two infusions of CAR T cells from haplo-HSCT donors. Five (83.33%) achieved minimal residual disease (MRD)-negative remission; one patient was discharged automatically without evaluation after developing severe thrombotic microangiopathies. Four of five responsive patients relapsed after 2-7 months, and one died of sepsis following MRD-negative remission after a second infusion. None of the other second infusion recipients achieved a second complete remission. Five patients (83.33%) experienced eight courses of grade 1-3 cytokine release syndrome; two were treated with tocilizumab. Two (33.3%) and one patient developed grade 2 and 3 acute graft-versus-host disease (aGVHD), respectively; the former was controlled with glucocorticoids. Donor-derived CAR T-cell infusion seems be effective and safe for relapsed B-ALL after haplo-HSCT, although larger clinical studies are needed.