Ph+急性B淋巴细胞白血病行CAR-T细胞治疗后接受异基因造血干细胞移植或酪氨酸激酶抑制剂的疗效及安全性分析  

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

作　　者：施艺 薛磊 许倩文 徐慧[2] 刘欣[2] 朱小玉 刘会兰 孙自敏 王兴兵 SHI Yi;XUE Lei;XU Qianwen;XU Hui;LIU Xin;ZHU Xiaoyu;LIU Huilan;SUN Zimin;WANY Xingbing(Department of Hematology,Anhui Provincial Hospital Affiliated of Anhui Medical University,Hefei,230001,China;Department of Hematology,the First Affiliated Hospital of University of Science and Technology of China)

机构地区：[1]安徽医科大学附属省立医院血液科,合肥230001 [2]中国科学技术大学附属第一医院(安徽省立医院)血液科

出　　处：《临床血液学杂志》2023年第11期779-783,共5页Journal of Clinical Hematology

基　　金：国家自然科学基金(No:82170221)。

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。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.

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 

分 类 号：R733.71[医药卫生—肿瘤]