CAR-T细胞桥接异基因造血干细胞移植治疗复发/难治急性B淋巴细胞白血病的临床分析

CAR T-cell bridging to allo-HSCT for relapsed/refractory B-cell acute lymphoblastic leukemia:the follow-up outcomes

目的研究嵌合抗原受体T细胞(CAR-T)细胞治疗桥接异基因造血干细胞移植(allo-HSCT)治疗复发/难治急性B淋巴细胞白血病(R/R B-ALL)的疗效及安全性。方法回顾性分析2017年1月至2019年5月于苏州大学附属第一医院行CAR-T细胞治疗桥接allo-HSCT的50例R/R B-ALL患者的临床资料,分析CAR-T细胞治疗前、后及allo-HSCT前不同骨髓微小残留病(MRD)水平患者总生存(OS)率、无事件生存(EFS)率、累积复发率(CIR)、移植相关死亡率(TRM)。结果全部患者共行55例次CAR-T细胞治疗,CAR-T细胞治疗反应率、严重细胞因子释放综合征(CRS)发生率分别为92%、28%。未发生治疗相关死亡。CAR-T细胞输注至allo-HSCT的中位时间为54(26~232)d。CAR-T细胞输注后中位随访637(117~1097)d,1年OS、EFS率分别为(80.0±5.7)%、(60.0±6.9)%。移植后1年CIR、TRM分别为(28.0±0.4)%、(8.0±0.2)%。CAR-T细胞输注后及allo-HSCT前骨髓MRD<0.01%患者1年EFS率更高[(70.0±7.2)%、(20.0±12.6)%,P<0.001;(66.7±7.5)%对(36.4±14.5)%,P=0.008],CIR更低[(25.0±0.5)%、(70.0±2.6)%,P<0.001;(23.1±0.5)%、(45.4±2.6)%,P=0.038]。结论CAR-T细胞治疗桥接allo-HCT对于复发/难治B-ALL是一种安全有效的治疗策略。

Objective This study aims to investigate the efficacy and safety of chimeric antigen receptor(CAR)T-cell bridging allogeneic hematopoietic stem cell transplantation(allo-HSCT)in the treatment of recurrent and refractory acute B-lymphocytic leukemia(R/R B-ALL).Methods A total of 50 R/R B-ALL patients who underwent CAR T-scell therapy to bridge allo-HSCT in the First Affiliated Hospital of Soochow University from January 2017 to May 2019 were retrospectively analyzed.The overall survival(OS)rate,event-free survival(EFS)rate,cumulative recurrence rate(CIR),and transplant-related mortality(TRM)of patients with different bone marrow minimal residual disease(MRD)levels were analyzed before and after CAR T-cell infusion and before allo-HSCT.Results The response rate of CAR T-cell therapy and the incidence rate of severe cytokine release syndrome were 92%and 28%,respectively.During 55 infusions,no treatment-related deaths occurred in any of the patients.The median time of CAR T-cell infusion to allo-HSCT was 54(26-232)days,the median follow-up time after CAR T-cell infusion was 637(117-1097)days,and the 1-year OS and EFS rates were(80.0±5.7)%and(60.0±6.9)%.The 1-year CIR and TRM after allo-HSCT were(28.0±0.4)%and(8.0±0.2)%.After CAR T-cell infusion and before allo-HSCT,patients with bone marrow MRD<0.01%had a significantly longer EFS[(70.0±7.2)%vs(20.0±12.6)%,P<0.001;(66.7±7.5)%vs(36.4±14.5)%,P=0.008]and lower CIR[(25.0±0.5)%vs(70.0±2.6)%,P<0.001;(23.08±0.47)%vs(45.45±2.60)%,P=0.038].Conclusion CAR T-cell therapy bridging allo-HSCT is safe and effective for recurrent and refractory B-ALL.