Efficacy and safety analysis of allogeneic hematopoietic stem cell transplantation or tyrosine kinase inhibitors after CAR-T cell therapy for Philadelphia chromosome-positive acute B lymphoblastic leukemia
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摘要: 目的 回顾性分析费城染色体阳性急性B淋巴细胞白血病(Ph+acute B-lymphocytic leukemia，Ph+B-ALL)患者行靶向CD19的嵌合抗原受体T细胞(chimeric antigen receptor T-cell，CAR-T)治疗达完全缓解后，采用随访观察、酪氨酸激酶抑制剂(tyrosine kinase inhibitors，TKIs)维持治疗或异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation，allo-HSCT)巩固治疗的疗效及安全性。方法 收集2017—2021年行自体CD19 CAR-T细胞治疗并获得完全缓解的Ph+B-ALL患者22例，根据CAR-T细胞治疗达完全缓解后治疗方式不同分为3组：随访观察组(5例)，CAR-T+TKIs组(11例)，CAR-T+移植组(6例)，比较各组的总生存期、无复发生存期及不良反应。结果 22例患者中男女各11例，中位年龄34(7~66)岁。随访观察组、CAR-T+TKIs组、CAR-T+移植组的中位生存时间分别为9.7(95%CI 9.06~10.34)个月、17.1(95%CI 9.98~24.22)个月、56.8(95%CI 38.63~74.97)个月，1年无复发生存率分别为0、45.5%、100%。在安全性方面，移植后共4例出现急性移植物抗宿主病，1例出现慢性移植物抗宿主病，不良反应均可控，无移植相关死亡，CAR-T+TKIs组无严重的药物相关不良反应。结论 Ph+ALL行CAR-T细胞治疗后达完全缓解的患者，口服TKIs维持治疗或进行allo-HSCT可改善长期生存；与口服TKIs维持治疗相比，allo-HSCT能进一步降低早期复发风险。
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关键词:
- 费城染色体 /
- 急性B淋巴细胞白血病 /
- 嵌合抗原受体T细胞 /
- 异基因造血干细胞移植 /
- 酪氨酸激酶抑制剂
Abstract: Objective To analyze the efficacy and safety of follow-up observation, tyrosine kinase inhibitors(TKIs), or allogeneic hematopoietic stem cell transplantation(allo-HSCT) in patients with Philadelphia chromosome-positive acute B lymphoblastic leukemia(Ph+B-ALL) who received CD19 chimeric antigen receptor T-cell(CAR-T) therapy to achieve complete remission(CR).Methods From 2017 to 2021, 22 patients with Ph+B-ALL who achieved CR after receiving autologous CD19 CAR-T cell therapy were divided into follow-up observation group(5 cases), CAR-T+TKIs group(11 cases) and CAR-T+HSCT group(6 cases). The overall survival, relapse-free survival and adverse events were compared among the groups.Results Among the 22 patients in this study, 11 cases were male and 11 cases were female, with a median age of 34(7-66) years old. The median overall survival in follow-up observation group, CAR-T+TKIs group and CAR-T+HSCT group were 9.7(95%CI 9.06-10.34) months, 17.1(95%CI 9.98-24.22) months, and 56.8(95%CI 38.63-74.97) months, respectively, and the 1-year relapse-free survival were 0, 45.5% and 100%, respectively. In terms of safety, 4 cases of acute graft-versus-host disease and 1 case of chronic graft-versus-host disease occurred after transplantation, and the adverse events were all controllable, with no transplant-related death. There were no serious drug-related adverse events in the CAR-T+TKIs group.Conclusion TKIs maintenance therapy or allo-HSCT improves long-term survival in Ph+B-ALL patients who achieve CR after CAR-T cell therapy. Compared to the maintenance therapy with TKIs, allo-HSCT provides a further reduction in the risk of early relapse. -
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表 1 CAR-T细胞治疗前3组患者基线特征比较
基线特征 CAR-T+移植组(6例) CAR-T+TKIs组(11例) 随访观察组(5例) 统计量 P 年龄/岁 38(13.75，44) 31(20，49) 39(33，50) 0.584 0.567 性别/例(%) 4.248 0.153 男 5(83.3) 5(45.5) 1(20.0) 女 1(16.7) 6(54.5) 4(80.0) 复发次数/例(%) 1.086 0.737 < 2 3(50.0) 4(36.4) 1(20.0) ≥2或未缓解 3(50.0) 7(63.6) 4(80.0) CAR-T前移植史/例(%) 0 2(18.2) 1(20.0) 1.340 0.571 骨髓原始细胞比例/% 70.5(12.0，83.0) 60.3(38.6，74.8) 78.8(23.4，87.3) 1.545 0.462 髓外病变/例(%) 2(33.3) 2(18.2) 2(40.0) 1.256 0.569 
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