Chen Yuhong, Cheng Yifei, Suo Pan, Yan Chenhua, Wang Yu, Chen Yao, Han Wei, Xu Lanping, Zhang Xiaohui, Liu Kaiyan, Chang Lungji, Xiao Lei, Huang Xiaojun
Peking University People's Hospital, Peking University Institute of Haematology, Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Collaborative Innovation Centre of Haematology, Peking University, Beijing, China.
Shenzhen Geno-Immune Medical Institute, Beijing, China.
Br J Haematol. 2017 Nov;179(4):598-605. doi: 10.1111/bjh.14923. Epub 2017 Oct 26.
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.
复发是单倍体相合造血干细胞移植(haplo-HSCT)后B细胞急性淋巴细胞白血病(B-ALL)患者治疗失败的常见原因,HSCT后对供体淋巴细胞输注无反应者预后极差。尽管供体来源的靶向CD19的嵌合抗原受体修饰(CAR)T细胞有可能治愈白血病,但其在haplo-HSCT后复发的B-ALL病例中的有效性和安全性尚未得到证实。2015年1月至2017年1月期间,分别有2例和4例患者接受了来自haplo-HSCT供体的1次和2次CAR T细胞输注。5例(83.33%)实现了微小残留病(MRD)阴性缓解;1例患者在发生严重血栓性微血管病后未经评估自动出院。5例有反应的患者中有4例在2 - 7个月后复发,1例在第二次输注后MRD阴性缓解后死于败血症。其他接受第二次输注的患者均未实现第二次完全缓解。5例患者(83.33%)经历了8个疗程的1 - 3级细胞因子释放综合征;2例接受了托珠单抗治疗。分别有2例(33.3%)和1例患者发生了2级和3级急性移植物抗宿主病(aGVHD);前者用糖皮质激素控制。供体来源的CAR T细胞输注对haplo-HSCT后复发的B-ALL似乎有效且安全,尽管需要更大规模的临床研究。