摘要
目的:分析CD19嵌合抗原受体T(CAR-T)细胞治疗复发难治B细胞淋巴瘤患者疗效不佳的因素。方法:招募自2017年2月至2019年1月就诊于天津市第一中心医院血液科的34例复发难治B细胞淋巴瘤患者进行研究。患者均接受CD19 CAR-T细胞治疗,评估其疗效、分析疗效不佳的因素以及不良反应。结果:34例复发难治B细胞淋巴瘤患者输注CD19 CAR-T细胞后,总有效率为58.8%(20/34),完全缓解率为41.2%(14/34)。有效组共20例,疗效不佳组14例。两组患者CD19 CAR-T细胞输注数量分别为8.6(5.0~12.7)×10^6/kg和9.7(5.8~15.0)×10^6/kg(P=0.654);外周血检测CAR-T细胞扩增数量,有效组和疗效不佳组CD19 CAR-T细胞占T淋巴细胞百分比中位数分别为10.28%(3.92%~44.16%)和4.05%(0.92%~28.63%),有效组比疗效不佳组CAR-T细胞扩增的比例更高,两者差异无统计学意义(P=0.371)。单因素方法分析两组疗效不佳因素,提示具有巨块型肿物是影响CD19 CAR-T细胞疗效的不利因素(P=0.001)。应用logistic回归多因素分析,结果显示具有巨块型肿物特征仍然是患者CD19 CAR-T细胞疗效不佳的独立预后因素(P=0.005,OR=0.039)。34例复发难治B细胞淋巴瘤患者输注CD19 CAR-T后,70.6%(24/34)患者发生不同程度的不良反应,主要为细胞因子释放综合征(CRS),出现发热的中位时间为输注后第3天(第0~11天),其中16例为1级CRS,7例为2级CRS,1例为3级CRS,经过糖皮质激素以及对症支持治疗后均好转。结论:CD19 CAR-T细胞疗法在CD19+B细胞淋巴瘤治疗中有一定效果,具有巨块型肿物特征可能是应用CAR-T疗效不佳的因素。
Objective To investigate the factors influencing the efficacy of CD19 chimeric antigen receptor T(CAR-T)cells in the treatment of patients with relapsed refractory B cell lymphoma and to provide evidence for further improvement of CAR-T efficacy.Methods A total of 34 patients with relapsed and refractory B-cell lymphoma were recruited from the Department of Hematology of Tianjin First Central Hospital from February 2017 to January 2019.All patients received CD19 CAR-T cell therapy.These patients were evaluated for efficacy,factors with poor efficacyand adverse effects.Results The overall response rate was 58.8%(20/34)and the complete remission rate was 41.2%(14/34)after infusion of CD19 CAR-T cells in 34 patients with relapsed refractory B cell lymphoma.According to the efficacy of CAR-T cells,patients were divided into two groups,20 in the effective group and 14 in the poorly effective group.The median am ount of CD19 CAR-T cell infusions in these two groups were 8.6(5.0-12.7)×10^6/kg and 9.7(5.8-15.0)×10^6/kg,respectively,and the difference was not statistically significant(P=0.654).The percentage of CD19 CAR-T cells in the effective group and the poorly treated group was 10.28%(3.92%-44.16%)and 4.05%(0.92%-28.63%),respectively.The effective group had a higher proportion of CAR-T cells than the poorly treated group,but the difference was not statistically significant(P=0.371).The presence of massive mass was an unfavorable factor affecting the efficacy of CD19 CAR-T cells and the difference was statistically significant(P=0.001).Logistic regression multivariate analysis showed that the characteristics of massive tumors were still independent prognostic factors for poor efficacy of CD19 CAR-T cells(P=0.005,OR=0.039).Of all 34 patients,there were 70.6%(24/34)who showed varying degrees of adverse reactions after the infusion of CD19 CAR-T cells,mainly cytokines release syndrome(CRS).The median time of occurrence of fever was on the third day after infusion(0-11th)day.16 patients were with grade 1 CRS,7 with grad
作者
肖霞
袁婷
孟娟霞
江嫣雨
曹雅青
李青
孙瑞
赵明峰
Xiao Xia;Yuan Ting;Meng Juanxia;Jiang Yanyu;Cao Yaqing;Li Qing;Sun Rui;Zhao Mingfeng(Graduate School,Tianjin Medical University,Tianjin 300070,China;Department of Hematology,Tianjin.First Central Hospital,Tianjin 300192,China)
出处
《中华医学杂志》
CAS
CSCD
北大核心
2020年第8期593-598,共6页
National Medical Journal of China
基金
国家自然科学基金(81970180)。