摘要
目的 分析双靶点CD19/CD22嵌合抗原受体T(CAR-T)细胞治疗混合谱系白血病基因重排(MLL-r)阳性难治/复发急性B系淋巴细胞白血病(R/R B-ALL)患儿的有效性及安全性。方法 回顾性分析2019年10月至2021年11月接受双靶点CD19/CD22 CAR-T治疗的MLL-r阳性R/R B-ALL患儿的临床资料。结果 共纳入37例MLL-r阳性R/R B-ALL患儿,男24例、女13例,诊断时中位年龄1.2(0.5~2.6)岁,其中17例(45.9%)为婴儿白血病。CAR-T细胞输注后中位时间9(7~13)天,37例患儿的完全缓解率达100%。中位随访时间28.2(11.3~30.9)个月,3年总体生存(OS)率为67.6%(95%CI:52.5%~82.7%),3年无事件生存率为59.5%(95%CI:43.6%~75.4%)。75.7%(28/37)的患者在CAR-T细胞治疗后接受过异基因造血干细胞移植,移植距离CAR-T细胞输注的中位时间为83(61~92)天。接受巩固性移植与未接受患儿的2年OS分别为75.0%(95%CI:58.9~91.1%)与44.4%(95%CI:11.9%~76.9%),差异无统计学意义(P=0.068)。35.1%(13/37)的患儿复发,中位复发时间为156(86~202)天,其中4例为CD19、CD22双阳性复发,2例CD19、CD22双阴性复发,4例单纯CD19阴性复发,1例淋系向髓系转化,另2例不明确。97.3%(36/37)患儿发生了细胞因子释放综合征,11例(29.7%)达到了3~4级,5例(13.5%)患儿出现了免疫效应细胞相关神经毒性综合征;无CAR-T细胞治疗合并症导致的死亡。结论 CD19/CD22 CAR-T细胞治疗可有效诱导MLL-r阳性儿童R/R B-ALL获得快速缓解,且不良反应可耐受。
Objective To analyze the efficacy and safety of dual-targeted CD19/CD22 chimeric antigen receptor T-cells(CAR-T)in the treatment of refractory/relapsed B-lineage acute lymphoblastic leukemia(B-ALL)in children with MLL gene rearrangement(MLL-r).Methods The clinical data of children with MLL-r positive R/R B-ALL treated with dual-targeted CD19/CD22 CAR-T therapy between October 2019 and November 2021 were retrospectively analyzed.Results A total of 37 children(24 boys and 13 girls)with MLL-r positive R/R B-ALL were included and the median age was 1.2(0.5-2.6)years at diagnosis,of whom 17(45.9%)had infantile leukemia.At a median time of 9(7-13)days after CAR-T cell infusion,37 patients achieved a complete response rate of 100%.With a median follow-up of 28.2(11.3 to 30.9)months,the 3-year overall survival rate was 67.6%(95%CI:52.5 to 82.7%),and the 3-year event-free survival rate was 59.5%(95%CI:43.6 to 75.4%).Twenty-eight patients(75.7%)underwent allogeneic hematopoietic stem cell transplantation after CAR-T cell therapy,and the median time between CAR-T infusion and transplantation was 83(61 to 92)days.The 2-year OS for children who received consolidation grafts was 75.0%(95%CI:58.9 to 91.1%),compared to 44.4%(95%CI 11.9 to 76.9%)for those who did not receive grafts.The difference between the two groups was not statistically significant(P=0.068).A total of 13 patients(35.1%)relapsed,and the median time from cell infusion to recurrence was 156(86 to 202)days.Among them,4 cases had double-positive recurrence of CD19 and CD22,2 cases had double-negative recurrence of CD19 and CD22,4 cases had CD19-negative recurrence,1 case had myeloid transformation,and the other 2 cases were unclear.Cytokine release syndrome occurred in 97.3%(36/37)of patients in this study,with 29.7%(11/37)achieved grades 3 to 4.Immune effector cell-associated neurotoxicity syndrome was observed in 5(13.5%)patients.There were no deaths due to CAR-T comorbidities.Conclusions CD 19/CD 22 CAR-T cell therapy is effective in inducing rapid remission in MLL-r R/R childhood B-lineage acute lymphoblastic leukemia with tolerable side effects.
作者
杨柳
苏萌
张婧
安康
蔡娇阳
钱娟
汤燕静
李本尚
YANG Liu;SU Meng;ZHANG Jing;AN Kang;CAI Jiaoyang;QIAN Juan;TANG Yanjing;LI Benshang(Department of Hematology/Oncology,Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2024年第10期888-894,共7页
Journal of Clinical Pediatrics
基金
国家自然科学基金项目(No.81670174)。
