供者CD19嵌合抗原受体T淋巴细胞治疗异基因造血干细胞移植后复发急性B淋巴细胞白血病临床分析

Clinical analysis of donor-derived CD19 chimeric antigen receptor T lymphocytes for the treatment of recu-rrent acute B-cell leukemia after allogeneic hematopoietic stem cell transplantation

目的探讨供者来源CD19嵌合抗原受体T淋巴细胞(CD19 CAR-T)治疗对异基因造血干细胞移植后复发急性B淋巴细胞白血病的疗效及不良反应,分析影响治疗因素。方法回顾性分析2015年7月至2017年10月5例在首都医科大学附属北京儿童医院接受供者CD19 CAR-T治疗患儿的治疗及随访资料。总结输注治疗疾病状态、预处理方案、回输细胞剂量及治疗后不良反应和相关免疫学指标变化,并追踪随访治疗结果。结果1例患儿对治疗无反应。4例患儿在4周内获得形态学缓解或微小残留病变(MRD)转阴,中位作用时间为14 d。外周血CAR-T细胞高峰出现在回输后2周左右。截至最后随访日期,接受治疗的患儿中死亡2例,存活3例,死亡原因均为原发病进展,存活病例中2例为无病生存,1例为CD19阴性髓外复发后带瘤生存。治疗不良反应主要为细胞因子释放综合征(CRS)反应,通常出现在治疗后1~2周;此外,1例患儿出现中枢神经系统异常,2例患儿出现可疑移植物抗宿主病表现。结论供者CD19 CAR-T对移植后复发急性B淋巴细胞白血病有良好的短期效果,长期疗效还需进一步观察;CRS为治疗最常见不良反应;治疗靶点脱失、CAR-T细胞耗竭是导致治疗失败的主要原因。

Objective To discuss the cure effect and side effects of donor anti-CD19 chimeric antigen receptor T lymphocytes(CD19 CAR-T)for treating recurrent acute B-cell leukemia after allogeneic hematopoietic stem-cell transplantation(Allo-HSCT), and to analyze the influencing factors for this therapy. Methods The clinical data of 5 acute B-cell leukemia patients were analyzed retrospectively who relapsed after Allo-HSCT and received donor CD19 CAR-T therapy at Beijing Children′s Hospital from July 2015 to October 2017.Disease status before infusion, conditioning regimen, reinfusion cell dose, and side-effect of CAR-T infusion, changes in the related immunological indicators, and follow-up treatment results were investigated. Results One patient had no effect, other patients got remission or minimal residual disease(MRD) negative within 4 weeks after CAR-T infusion, and the middle time was 14 days.Peripheral CAR-T peak happened 2 weeks after CAR-T infusion.By the last follow, 2 patients died of leukemia, 3 patients were alive, and 1 case of them lived with tumor after CD19 negative relapse, others lived with disease-free condition.Cytokine release syndrome(CRS) was the most common side effect, happening in 1 to 2 weeks after infusion, 1 patient had neurologic toxicities, and 2 patients had suspicious graft-versus-host disease. Conclusions Donor CD19 CAR-T therapy has a good short-term effect for relapsed B-cell leukemia patients after Allo-HSCT, but long-term effect requires further observation;CRS is the most common side-effect.Off-target and cell exhaustion are the main reasons for defeat.