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 CD19/CD22 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.