CAR-T治疗复发/难治急性B淋巴细胞白血病的长期生存及影响因素的临床分析  

Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia

作　　者：王一[1] 高秋英 王晖[1] 张玎[1] 高瑛[1] 苗玉迪[1] 翟欣辉[1] 胡星星 茹杏丽 张维华[1] Wang Yi;Gao Qiuying;Wang Hui;Zhang Ding;Gao Ying;Miao Yudi;Zhai Xinhui;Hu Xingxing;Rui Xingli;Zhang Weihua(Department of Hematology,Shaanxi Provincial People's Hospital,Xi'an 710068,China)

机构地区：[1]陕西省人民医院血液内科,西安710068

出　　处：《中华血液学杂志》2023年第10期800-804,共5页Chinese Journal of Hematology

摘　　要：目的分析嵌合抗原受体T细胞(CAR-T)治疗复发/难治急性B淋巴细胞白血病(R/R B-ALL)获完全缓解(CR)患者的长期生存及其影响因素。方法收集2015年5月至2018年7月就诊于陕西省人民医院接受靶向CD19的CAR-T细胞治疗并获得CR的R/R B-ALL患者的临床信息。采用Kaplan-Meier法评估患者的总生存(OS)和无白血病生存(LFS),并通过Cox等比例风险回归分析CAR-T治疗后患者预后的影响因素。结果纳入的38例R/R B-ALL患者中,男性患者21例,中位年龄25(6~59)岁,中位OS时间为18(95%CI 3~33)个月。多因素Cox回归分析显示:MLL-AF4融合基因阳性是OS及LFS的独立危险因素(OS:HR=4.888,95%CI 1.375~17.374,P=0.014;LFS:HR=6.683,95%CI 1.815~24.608,P=0.004);接受维持治疗是OS及LFS的独立保护因素(OS:HR=0.153,95%CI 0.054~0.432,P<0.001;LFS:HR=0.138,95%CI 0.050~0.382,P<0.001);MRD转阴患者LFS获益(HR=0.209,95%CI 0.055~0.797,P=0.022),但OS差异无统计学意义(P=0.111);具有高肿瘤负荷的患者在0.1的水平上是OS及LFS的危险因素(OS:HR=2.662,95%CI 0.987~7.184,P=0.053;LFS:HR=2.452,95%CI 0.949~6.339,P=0.064)。结论高肿瘤负荷和高危遗传学可能会影响R/R B-ALL患者接受CAR-T治疗后的长期生存,予以来那度胺为基础的维持治疗有可能改善患者的长期预后。Objective To analyze the survival and influencing factors of chimeric antigen receptor(CAR)T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia(R/R B-ALL).Methods Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and leukemia-free survival(LFS)times of patients,and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy.Results Among the 38 patients with R/R B-ALL,21 were men,with a median age of 25(6-59)years and a median OS time of 18(95%CI 3-33)months.Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS(OS:HR=4.888,95%CI 1.375-17.374,P=0.014;LFS:HR=6.683,95%CI 1.815-24.608,P=0.004).Maintenance therapy was a protective factor for OS and LFS(OS:HR=0.153,95%CI 0.054-0.432,P<0.001;LFS:HR=0.138,95%CI 0.050-0.382,P<0.001).In patients with MRD negative conversion,LFS benefit(HR=0.209,95%CI 0.055-0.797,P=0.022)and OS difference was statistically insignificant(P=0.111).Moreover,patients with high tumor burden were risk factors for OS and LFS at the level of 0.1(OS:HR=2.662,95%CI 0.987-7.184,P=0.053;LFS:HR=2.452,95%CI 0.949-6.339,P=0.064).Conclusion High tumor burden and high-risk genetics may affect the longterm survival rate of patients with R/R B-ALL receiving CAR-T,and lenalidomide-based maintenance therapy may improve their prognosis.

关 键 词：急性B淋巴细胞白血病 嵌合抗原受体T细胞 复发/难治 预后 

分 类 号：R733.71[医药卫生—肿瘤]