嵌合抗原受体T细胞治疗在儿童难治性急性B淋巴细胞白血病中的应用价值

Analysis of the value of chimeric antigen receptor T cell therapy in refractory B-acute lymphoblastic leukemia in children

目的 探讨嵌合抗原受体T细胞(CAR-T)治疗在儿童难治性急性B淋巴细胞白血病(R B-ALL)中的应用价值。方法 收集60例行CAR-T治疗的R B-ALL患儿的临床资料,分析CAR-T治疗后近期疗效的影响因素并探讨其安全性。结果 CAR-T治疗后30天完全缓解率为83.33%(50/60)。完全缓解和未缓解患儿淋巴细胞清除化疗前乳酸脱氢酶(LDH)值和淋巴细胞清除化疗前肿瘤负荷比较,差异均有统计学意义(P﹤0.01)。淋巴细胞清除化疗前LDH值、淋巴细胞清除化疗前肿瘤负荷均是R B-ALL患儿CAR-T治疗后近期疗效的影响因素(P﹤0.05)。CAR-T治疗后的细胞因子释放综合征(CRS)、脱靶效应、粒细胞减少、血小板减少、贫血、转氨酶升高、神经毒性、感染发生率分别为86.67%、83.33%、73.33%、71.67%、43.33%、33.33%、16.67%、13.33%。发生3~4级CRS患儿的白细胞介素-6(IL-6)峰值、白细胞介素-10(IL-10)峰值、γ干扰素(IFN-γ)峰值均明显高于发生1~2级CRS的患儿,差异均有统计学意义(P﹤0.01)。输注CAR-T后,发生CRS患儿的IL-6、IL-10、IFN-γ水平均明显高于输注前,差异均有统计学意义(P﹤0.01)。结论 CAR-T在R B-ALL治疗中疗效较为确切,虽有不良反应但存在可控性,CRS与多种炎性因子存在一定关联,尽早干预CRS可有效提升CAR-T的治疗安全性。

Objective To investigate the value of chimeric antigen receptor T cell(CAR-T)therapy in refractory B-acute lymphoblastic leukemia(R B-ALL)in children.Method The clinical data of 60 CAR-T treated children with R B-ALL were collected.The influencing factors for short-term efficacy after CAR-T treatment were analyzed and its safety was also discussed.Result Thirty days after the CAR-T treatment,the complete response rate was 83.33%(50/60).The lactate dehydrogenase(LDH)value and tumor load before lymphocyte clearance chemotherapy between complete response and non-complete response children were significantly different(P<0.01).LDH value and tumor load before lymphocyte clearance chemotherapy were risk factors for the short-term efficacy of CAR-T therapy in children with R B-ALL(P<0.05).The incidence of cytokine release syndrome(CRS),off-target effect,granulocytopenia,thrombocytopenia,anemia,transaminase elevation,neurotoxicity,and infections after CAR-T therapy were 86.67%,83.33%,73.33%,71.67%,43.33%,33.33%,16.67%,and 13.33%,respectively.The peak values of interleukin-6(IL-6),interleukin-10(IL-10),and interferon-γ(IFN-γ)in children who developed grade 3-4 CRS were significantly higher than those who developed grade 1-2 CRS,and the differences were statistically significant(P<0.01).After the infusion of CAR-T,the levels of IL-6,IL-10,and IFN-γin children who developed CRS were significantly higher than those before the infusion,and the differences were statistically significant(P<0.01).Conclusion The efficacy of CAR-T in the treatment of R B-ALL is relatively accurate,although the adverse events could not avoid,they are under control.CRS and a variety of inflammatory factors have a certain correlation,early intervention of CRS could effectively improve the safety of CAR-T treatment.