复发难治型ALL患者行CAR-T治疗后复发与外周血Foxp3^(+)Treg水平的相关性  

Correlations between recurrence and Foxp3^(+)Treg levels in peripheral blood of patients with recurrent refractory acute lymphoblastic leukemia after CAR-T immunotherapy

作　　者：王婉玲[1] 杨翠[1] 陈小双 高攀科 韩效林[1] WANG Wanling;YANG Cui;CHEN Xiaoshuang;HAN Xiaolin(Department of Hematology,the First Affiliated Hospital of Xinxiang Medical College,Henan Xinxiang 453100,China)

机构地区：[1]新乡医学院第一附属医院血液科,河南新乡453100

出　　处：《现代肿瘤医学》2021年第9期1566-1570,共5页Journal of Modern Oncology

基　　金：河南省医学科技攻关计划项目(编号:LHGJ20190434)。

摘　　要：目的:探究复发难治型急性淋巴细胞白血病(ALL)患者行嵌合抗原受体修饰T细胞(CAR-T)免疫疗法治疗后复发与外周血Foxp3^(+)Treg水平的相关性。方法:选择2014年02月至2018年03月于我院血液科行CAR-T治疗的45例复发难治型ALL患者作为研究对象,测定患者治疗前外周血Foxp3^(+)Treg水平,随访收集患者无进展生存时间(PFS),采用Kaplan-Meier法及COX比例风险回归模型分析患者预后的影响因素。结果:45例患者输注CAR-T后均定期监测,其中35例患者形态学完全缓解,治疗反应率为77.78%。以1年作为随访时间截点,复发组患者外周血Foxp3^(+)Treg水平显著高于未复发组,差异具统计学意义(P<0.05)。年龄≥8岁、CAR-T输注前肿瘤负荷<5%、外周血Foxp3^(+)Treg水平<10%患者PFS显著高于年龄<8岁、CAR-T输注前肿瘤负荷≥5%、外周血Foxp3^(+)Treg水平≥10%患者(P<0.05)。COX多因素分析示,在矫正年龄、CAR-T输注前肿瘤负荷等因素后,外周血Foxp3^(+)Treg水平是复发难治型ALL患者CAR-T治疗后复发的独立危险因素(P<0.05)。结论:外周血Foxp3^(+)Treg水平与复发难治型ALL患者CAR-T治疗后复发相关,在临床治疗中或许可通过采取一定辅助措施降低Foxp3^(+)Treg水平,提高治疗效果,降低复发风险。Objective:To explore the relationship between recurrence and Foxp3^(+)Treg levels in peripheral blood of patients with recurrent refractory acute lymphoblastic leukemia(ALL)after chimeric antigen receptor modified T cells(CAR-T)immunotherapy.Methods:Forty-five patients with recurrent refractory ALL who underwent CAR-T treatment in hematology department of the hospital from February 2014 to March 2018 were enrolled as the study subjects.Foxp3^(+)Treg levels in peripheral blood were measured before treatment.The progression-free survival(PFS)was collected by follow-up.The influencing factors of prognosis were analyzed by Kaplan-Meier method and COX proportional hazards regression model.Results:All the 45 patients were monitored regularly after CAR-T infusion.Among them,there were 35 cases with complete morphological remission,with treatment response rate of 77.78%.Taking 1 year as the cut-off point of follow-up time,Foxp3^(+)Treg levels in peripheral blood in recurrence group were significantly higher than those in non-recurrence group(P<0.05).PFS in patients with age not younger than 8 years old,tumor load lower than 5%before CAR-T infusion,level of peripheral blood Foxp3^(+)Treg lower than 10%was significantly higher than that with age younger than 8 years old,tumor load not lower than 5%before CAR-T infusion and level of peripheral blood Foxp3^(+)Treg not lower than 10%(P<0.05).COX multivariate analysis showed that after correcting age and tumor load before CAR-T infusion,level of peripheral blood Foxp3^(+)Treg was an independent risk factors of recurrence in patients with recurrent refractory ALL after CAR-T treatment(P<0.05).Conclusion:The level of Foxp3^(+)Treg in peripheral blood is related to recurrence in patients with recurrent refractory ALL after CAR-T treatment.In clinical treatment,some auxiliary measures may be taken to reduce level of Foxp3^(+)Treg,improve curative effect and reduce recurrence.

关 键 词：急性淋巴细胞白血病 嵌合抗原受体修饰T细胞 复发 预后 

分 类 号：R733.31[医药卫生—肿瘤]