CAR-T细胞治疗复发/难治急性B淋巴细胞白血病后免疫功能的变化及其相关因素分析  

Kinetics of immune function and relevant factors analysis after chimeric antigen receptor T cell therapy in relapsed or refractory acute B lymphoblastic leukemia

作　　者：李阳玉 薛磊 汪敏 徐慧[2] 杨林 王兴兵 LI Yangyu;XUE Lei;WANG Min;XU Hui;YANG Lin;WANG Xingbing(Department of Hematology,Anhui Provincial Hospital Affiliated of Anhui Medical University,Hefei,230001,China;Department of Hematology,the First Affiliated Hospital of University of Science and Technology of China,Division of Life Sciences and Medicine,University of Science and Technology of China;PersonGen-Anke Cellular Therapeutics Co.,Ltd)

机构地区：[1]安徽医科大学附属省立医院血液科,合肥230001 [2]中国科学技术大学附属第一医院(安徽省立医院)血液科 [3]博生吉安科细胞技术有限公司

出　　处：《临床血液学杂志》2022年第5期348-353,共6页Journal of Clinical Hematology

基　　金：安徽省科技重大专项(No:18030801126);安徽省科技攻关项目(No:1604a0802071)。

摘　　要：目的:分析靶向CD19的嵌合抗原受体T细胞(CAR-T)治疗复发/难治急性B淋巴细胞白血病(B-ALL)引起免疫功能的变化以及相关因素分析。方法:分析2016年10月—2020年10月接受靶向CD19 CAR-T细胞治疗复发/难治B-ALL患者的血常规、淋巴细胞亚群、免疫球蛋白变化、感染情况及相关因素。结果:共纳入52例复发/难治B-ALL患者,其中39例治疗后达完全缓解的患者中,出现中性粒细胞和(或)血小板减少(3级及3级以上)分别为38例(97.4%)、35例(89.7%),3例患者在输注1年后上述血细胞未恢复至正常水平,但均处于1~2级血细胞减少水平。23例患者进行了淋巴细胞亚群检测,21例(91.3%)患者在输注C AR-T细胞14天内出现CD4^(+)/CD8^(+)淋巴细胞比值下降;所有患者均出现B细胞发育不全,B细胞发育不全的中位发生时间为第7天(0~14)天。22例患者在CAR-T细胞输注后,分别有19例(86.4%)、21例(95.5%)、18例(81.8%)IgA、IgM、IgG较输注前减低,且既往行异基因造血干细胞移植的患者较未行移植的患者IgM下降更明显(P<0.05)。CAR-T细胞输注30天后仅1例因感染控制不佳死亡,其余患者无致命性感染发生。结论:复发难治B-ALL患者接受CD19CAR-T细胞治疗后,血细胞减少、免疫球蛋白水平下降较为常见,且IgM下降水平与既往是否行异基因造血干细胞移植有关,但相关致命性感染发生率较低。Objective:To explore the kinetics of immune function and relevant factors of CD19chimeric antigen receptor T cell(CD19CAR-T)therapy in relapsed/refractory acute B lymphoblastic leukemia(B-ALL).Methods:The kinetics of blood count,lymphocyte subsets,immunoglobulins and infection in patients who received CAR-T therapy from October 2016to October 2020were analyzed.Results:A total of 52patients with relapsed/refractory B-ALL were enrolled.Among the 39patients who obtained complete remission,neutropenia(≥grade 3)occurred in 38cases(97.4%),and thrombocytopenia(≥grade 3)occurred in 35cases(89.7%).Three patients did not reach normal levels of blood count after 1year,but all were at grade 1to 2cytopenia.Lymphocyte subsets were detected in 23patients,CD4/CD8ratio decreased in 21cases(91.3%)within 14days after CAR-T cell infusion.All 23patients developed B cell aplasia,and the median onset time of B cell aplasia was on day 7(0-14).After CAR-T cell infusion in 22patients,IgA,IgM,and IgG decreased in 19cases(86.4%),21cases(95.5%)and 18cases(81.8%),respectively,and patients received allogeneic hematopoietic stem cell transplantation had significantly lower IgM than that in patients without allogeneic hematopoietic stem cell transplantation(P<0.05).Only one patient died of infection on day 30after CAR-T cell infusion,and no fatal infection occurred in other patients,and no related factors were found.Conclusion:Cytopenia and immunoglobulin decrease are the common adverse events after CD19CAR-T cell therapy in patients with relapsed and refractory B-ALL,and the decrease of IgM is related to whether allogeneic hematopoietic stem cell transplantation was performed.The incidence of related fatal infections is low.

关 键 词：急性B淋巴细胞白血病 嵌合抗原受体T细胞治疗 CD19 血细胞 免疫功能 

分 类 号：R733.71[医药卫生—肿瘤]