Safety and efficacy of allogeneic donor-derived CD19 CAR-T therapy for the treatment of relapsed B-cell acute lymphoblastic leukemia after transplantation
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摘要: 目的 探讨供者CD19嵌合抗原受体T细胞(chimeric antigen receptor T cell，CAR-T)治疗在儿童急性B淋巴细胞白血病(B-cell acute lymphoblastic leukemia，B-ALL)接受异基因造血干细胞移植后复发患者中的疗效及安全性。方法 选择2018年1月至2020年12月我中心收治的14例采用供者CD19 CAR-T细胞治疗的移植后复发B-ALL的临床资料，评估其疗效及安全性。结果 14例患者在回输后1个月内均获得骨髓微小残留病阴性的完全缓解。所有患者均发生细胞因子释放综合征，严重细胞因子释放综合征(≥3级)者9例(64.3%)；4例发生免疫效应细胞相关神经毒性综合征，均经相应治疗后症状消失。中位随访时间为43.4(11.8~ 68.4)个月，5例复发，其中4例为移植后骨髓血液学复发患者，1例为移植后微小残留病水平复发患者，复发时CD19阳性2例，CD19阴性1例，另外2例表型不详，中位复发时间为13.4个月，3年总生存率为63%±13%，3年无白血病生存率为61%±14%。结论 供者CD19 CAR-T细胞治疗可有效治疗移植后复发B-ALL，但对回输前肿瘤负荷高的患者，建议再次缓解后桥接造血干细胞移植以改善长期生存情况。
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关键词:
- 供者嵌合抗原受体 /
- CD19 /
- 异基因造血干细胞移植 /
- 急性B淋巴细胞白血病 /
- 复发
Abstract: Objective To investigate the efficacy and safety of donor CD19 chimeric antigen receptor T cell(CAR-T) therapy in pediatric patients with B-cell acute lymphoblastic leukemia(B-ALL) who relapsed after allogeneic hematopoietic stem cell transplantation.Methods The clinical data of 14 patients with post-transplant relapsed B-ALL treated with donor CD19 CAR-T cell therapy were collected from January 2018 to December 2020, and the efficacy and safety of CAR-T cell therapy were evaluated.Results All of the 14 patients obtained negative minimal residual disease within one month after infusion. Cytokine release syndrome occurred in all patients, with 9 patients(64.3%) developed severe cytokine release syndrome(grade ≥3), and 4 patients developed immune effector cell-associated neurotoxicity syndrome, all of which disappeared after corresponding treatment. The median follow-up time was 43.4(11.8-68.4) months, and there were 5 cases of recurrence with a median recurrence time of 13.4 months. Four cases were identified as bone marrow relapse prior to CAR-T cell therapy, and only one case was minimal residual disease recurrence. At relapse, the CD19 immunophenotype on leukemia blasts was CD19+(2 cases), CD19－(1 case), and CD19 unknown(2 cases). The 3-year overall survival rate was 63%±13%, and the 3-year leukemia-free survival rate was 61%±14%.Conclusion Donor CD19 CAR-T cell therapy can effectively treat recurrent B-ALL after transplantation, but for patients with high tumor burden before infusion, it is recommended to bridge to hematopoietic stem cell transplantation after remission to improve long-term survival. -
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表 1 14例allo-HSCT后复发B-ALL患者的临床资料及接受CD19 CAR-T细胞治疗的疗效
例号 移植前疾病状态 遗传学异常 移植供者类型 移植后复发类型 预处理前骨髓形态缓解情况(原幼细胞比例) CAR-T后是否复发 预后 转归 LFS时间/月 OS时间/月 1 CR1 TCF3/PBX1 MSD MRD CR 否 11.8 11.8 死于二次移植后肺部排异 2 CR1 无 单倍型 血液学复发 47% 是 13.4 19.4 死于CD22 CAR-T后严重CRS 3 CR2 超二倍体 MSD 血液学复发 16% 是 6.3 20.8 死于二次移植后肺部排异 4 CR1 超二倍体 单倍型 MRD CR 是 18.1 26.3 死于骨髓复发 5 CR1 MLL-ENL阳性 单倍型 MRD CR 否 40.8 40.8 CR 6 CR1 无 单倍型 血液学复发 55.5% 否 43.1 43.1 CR 7 CR1 无 MSD 血液学复发 5% 是 40.4 43.4 死于骨髓复发 8 CR1 无 单倍型 血液学复发 49% 否 51.7 51.7 CR 9 CR1 MLL FISH重排阳性 MSD MRD CR 否 51.8 51.8 CR 10 CR1 MLL-AF1q阳性 单倍型 MRD CR 否 53.2 53.2 CR 11 CR2 MLL-AF10阳性 单倍型 MRD+EMR CR 否 54.6 54.6 CR 12 CR2 无 单倍型 血液学复发 8% 否 67.7 67.7 CR 13 CR2 TCF3/PBX1 单倍型 MRD CR 否 68.4 68.4 CR 14 CR2 IKZF1阳性，超二倍体 单倍型 血液学复发 88% 是 10.3 48.5 死于骨髓复发 
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