酪氨酸激酶抑制剂对CD19 CAR-T细胞在难治/复发Ph阳性急性淋巴细胞白血病中扩增的影响  

Influence of TKIs on proliferation of CD19 CAR-T cells in refractory/relapsed Ph+acute lymphoblastic leukemia

作　　者：吕翠翠 李新[1] 李青[1] 穆娟[1] 王嘉[1] 袁婷 江嫣雨 邓琦[1] Lyu Cuicui;Li Xin;Li Qing;Mu Juan;Wang Jia;Yuan Ting;Jiang Yanyu;Deng Qi(Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China)

机构地区：[1]天津市第一中心医院血液科,天津300192

出　　处：《临床荟萃》2020年第10期909-913,共5页Clinical Focus

基　　金：国家自然科学基金资助项目——GATA4在人iPSCs定向肝窦内皮细胞分化中的功能及机制研究(81900186)。

摘　　要：目的观察酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)对CD19嵌合抗原受体修饰(CAR)T细胞在难治/复发Ph+急性淋巴细胞白血病(ALL)中的扩增、疗效及不良反应的影响。方法收集10例难治/复发Ph+ALL患者(TKIs组)和16例难治/复发Ph阴性B-ALL患者(非TKIs组),TKIs组给予TKIs口服。在输注CD19 CAR-T细胞后第0、4、7、14、21和28天分别检测外周血中CD19 CAR-T细胞,分析两组输注后的疗效及不良反应。结果TKIs组外周血中CD19 CAR-T细胞的峰值高于非TKIs组,两组差异有统计学意义(P=0.0037);两组细胞因子峰值、细胞因子释放综合征(CRS)分级、第14天完全缓解(CR)率、总生存率(OS)和无病生存率(DFS)差异均无统计学意义(P>0.05)。结论TKIs促进CD19 CAR-T细胞在难治/复发Ph+ALL中的扩增,不抑制CD19 CAR-T细胞的疗效,不加重其不良反应,近期及远期疗效肯定。Objective To observe the influence of tyrosine kinase inhibitors(TKIs)on the proliferation,efficacy and adverse reactions(AEs)of CD19 CAR-T cells in refractory/relapsed Ph+acute lymphoblastic leukemia(Ph+ALL).Methods Ten patients with refractory/relapsed Ph+ALL(TKIs group)and 16 patients with refractory/relapsed Ph-negative B-ALL(non-TKIs group)were collected,and TKIs group was given TKIs orally.CD19 CAR-T cells were detected in peripheral blood at 0,4,7,14,21 and 28 days after infusion,and the clinical efficacy and AEs of two groups were analyzed.Results The peak value of CD19 CAR-T cells in peripheral blood in TKIs group was higher than that in non-TKIs group,with statistically significant differences between the two groups(P=0.0037).There were no statistically significant differences in cytokine peak,cytokine release syndrome(CRS)grading,the complete response(CR)rate at day 14,overall survival(OS)rate and disease-free survival(DFS)rate between the two groups(P>0.05).Conclusion TKIs promoted the proliferation of CD19 CAR-T cells in refractory/relapsed Ph+ALL,without inhibiting the clinical efficacy of CD19 CAR-T cells and aggravating AEs,which showed positively short-term and long-term effects.

关 键 词：白血病 淋巴样 嵌合抗原受体 酪氨酸激酶抑制剂 费城染色体阳性 

分 类 号：R733.7[医药卫生—肿瘤]