CD19 CAR-T细胞治疗难治/复发急性B淋巴细胞白血病儿童及青少年患者的疗效及安全性

doi:10.12372/jcp.2024.24e0207

摘要/Abstract

摘要：

目的探讨CD19嵌合抗原受体T细胞（CAR-T）治疗对于儿童及青少年难治/复发急性B淋巴细胞白血病（B-ALL）的疗效及安全性。方法回顾性分析2017年6月至2021年3月接受CD19 CAR-T治疗的<25岁难治/复发B-ALL患者的临床资料，评估该疗法的疗效及安全性。结果共纳入64例难治/复发B-ALL患者，男35例、女29例，中位年龄8.5（1.0~17.0）岁。CD19 CAR-T回输后1个月进行短期疗效评估，64例患者均获得完全缓解（CR）/完全缓解兼部分血细胞计数缓解（CRi），其中有62例患者达骨髓微小残留病灶（MRD）阴性。细胞因子释放综合征（CRS）及免疫效应细胞相关神经毒性综合征（ICANS）发生率分别为78.1%及23.4%。共22例患者复发，中位复发时间10.1个月，4年总生存（OS）率为（66.0±6.0）%，4年无白血病生存（LFS）率为（63.0±6.0）%。长期随访结果显示桥接异基因造血干细胞移植（allo-HSCT）患者的LFS和OS率均优于未桥接移植患者（4年LFS率：81.8%±6.2%对24.0%±9.8%，4年OS率：81.4%±5.9%对44.4%±11.2%；均P<0.01）。结论 CD19 CAR-T可有效治疗难治/复发B-ALL，输注后桥接allo-HSCT能进一步改善患者的长期生存情况。

关键词: 嵌合抗原受体, CD19, 难治, 复发, 急性B淋巴细胞白血病

Abstract:

Objective To explore the efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) in children and adolescents. Methods The clinical data of refractory/relapsed B-ALL patients<25 years old who received CD19 CAR-T therapy from June 2017 to March 2021 were retrospectively analyzed and the efficacy and safety of this therapy was evaluated. Results A total of 64 patients (35 boys and 29 girls) with refractory/relapsed B-ALL were included, and the median age was 8.5 (1.0-17.0) years old. One month following CD19 CAR-T infusion, a short-term effectiveness assessment of all 64 patients showed minimal residual disease (MRD) negative in 62 of them, and complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) in all 64 patients. The incidence rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 78.1 % and 23.4 %, respectively. Twenty-two patients experienced recurrence after infusion, with a median recurrence time of 10.1 months. The 4-year overall survival (OS) rate was 66.0 %±6.0 %, and the 4-year leukemia free survival (LFS) rate was 63.0 %±6.0 %. Long-term follow-up results demonstrated superior LFS and OS in patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) compared to those who were not bridged to transplantation (4-year LFS: 81.8 %±6.2 % vs. 24.0 %±9.8 %, 4-year OS: 81.4 %±5.9 % vs. 44.4 %±11.2 %; both P<0.01). Conclusions CD19 CAR-T therapy can effectively treat refractory/relapsed B-ALL, and bridging to HSCT after infusion can further improve the long-term survival outcomes in patients.

Key words: chimeric antigen receptor, CD19, refractory, relapsed, B-cell acute lymphoblastic leukemia

王毓, 薛玉娟, 左英熹, 贾月萍, 陆爱东, 曾慧敏, 张乐萍. CD19 CAR-T细胞治疗难治/复发急性B淋巴细胞白血病儿童及青少年患者的疗效及安全性[J]. 临床儿科杂志, 2024, 42(7): 583-588.

WANG Yu, XUE Yujuan, ZUO Yingxi, JIA Yueping, LU Aidong, ZENG Huimin, ZHANG Leping. Efficacy and safety of CD19 targeted CAR-T cells in the treatment of refractory/relapsed B-cell acute lymphoblastic leukemia in children and adolescents[J]. Journal of Clinical Pediatrics, 2024, 42(7): 583-588.

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临床特征	例数	构成比/%
性别
男	35	54.7
女	29	45.3
年龄
<10岁	38	59.4
≥10岁	26	40.6
融合基因
BCR/ABL	5	7.8
ETV6/RUNX1	7	10.9
KMT2A	3	4.7
TCF3/PBX1	7	10.9
其他	42	65.6
复杂染色体核型
是	6	9.4
否	48	75.0
不详	10	15.6
输注前髓外病变
是	10	15.6
否	54	84.4
输注前骨髓涂片
缓解	39	60.9
未缓解	25	39.1
输注前骨髓MRD
<0.1%	15	23.4
≥0.1%	49	76.6
输注前是否HSCT
是	7	10.9
否	57	89.1
CRS分级
0级	14	21.9
1~2级	27	42.2
3~4级	23	35.9
ICANS分级
0级	49	76.6
1~2级	10	15.6
3~4级	5	7.8

CRS分级	IL-6峰值/pg·mL^-1	CAR-T细胞扩增峰值/拷贝·μg DNA^-1
0~2级	20.8(11.4~80.5)	27 100.0(10 778.5~134 000.0)
3~4级	1 458.0(315.0~4 555.0)	251 499.0(69 901.0~475 000.0)
Z值	4.91	4.18
P	<0.001	<0.001