【摘要】 目的探讨CD19嵌合抗原受体T（CD19-CAR-T）细胞治疗复发/难治急性B淋巴细胞白血病（R/R B-ALL）的疗效及并发症。方法回顾性分析2016年1月至2018年1月14例接受CD19-CAR-T细胞治疗的R/R B-ALL患者的临床资料。监测CD19-CAR-T细胞回输后细胞因子水平（IFN-γ、TNF-α、IL-6、IL-8、IL-10、IL-17A、IL-18）以及C反应蛋白和铁蛋白水平,观察近期和远期疗效及细胞因子释放综合征（CRS）的发生情况。结果 14例患者回输CD19-CAR-T细胞总量的中位数为0.6×10⁶/kg。13例患者可进行d₂₈疗效评价,获完全缓解7例,部分缓解2例,无效4例,有效率为92.3%。体内CD19-CAR-T细胞数在d₁₀～d₂₁达到高峰,在d₉₀时能检测到较低水平的CD19-CAR-T细胞。全组中位总生存时间（OS）为10.2个月。14例患者均出现CRS,其中1级2例,2级6例,3级3例,4级2例,5级1例。CRS发生时,IL-6、IFN-γ、IL-10、C反应蛋白和铁蛋白水平明显升高。14例患者均出现发热,出现肝功能异常9例、心血管功能障碍3例、肾功能异常3例、胰腺炎1例、神经毒性7例以及呼吸衰竭2例。结论 CD19-CAR-T细胞治疗R/R B-ALL的近期疗效较好,但是CD19-CAR-T细胞体内维持时间短,早期容易复发。IL-6、IFN-γ、IL-10、C反应蛋白和铁蛋白水平升高有助于CRS的诊断。更多还原

【Abstract】 Objective To investigate the efficacy and complications of CD19 chimeric antigen receptor T（ CD19-CAR-T） cells in the treatment of relapses/refractory B-acute lymphocytic leukemia（ R/R B-ALL）. Methods Retrospective analysis was performed on 14 cases of R/R B-ALL treated with CD19-CAR-T cells from January 2016 to January 2018. The dramatic changes of cytokines（ including interleukin IFN-γ,TNF-α,IL-6,IL-8,IL-10,IL-17 A,IL-18）,C reactive protein and ferritin were monitored. The short-term and longterm efficacy as well as cytokine release syndrome（ CRS） were observed. Results The median amount of CD19-CAR-T cells transfusion in14 patients was 0. 6×10⁶/kg. Thirteen patients could be evaluated on d₂₈,7 cases achieved complete remission,2 cases achieved partial remission,4 cases were ineffective,and the effective rate was 92. 3%. The number of CD19-CAR-T cells in vivo reached the peak from d₁₀ to d₂₁,and a lower level of CD19-CAR-T cells still could be detected at d₉₀. The median overall survival（ OS） was 10. 2 months. All the 14 patients had CRS symptoms,including 2 cases of grade 1,6 cases of grade 2,3 cases of grade 3,2 cases of grade 4 and 1 case of grade 5.The level of IL-6,IFN-γ,IL-10,C-reactive protein and ferritin increased,when CRS occured. Fever was found in 14 cases,liver dysfunction in 9 cases,cardiovascular dysfunction in 3 cases,renal dysfunction in 3 cases,pancreatitis in 1 case,neurotoxicity in 7 cases and respiratory failure in 2 cases. Conclusion The short-term efficacy of CD19-CAR-T cells in the treatment of R/R B-ALL is satisfactory,but CD19-CART cells maintain a short time in vivo,and the disease is easy to relapse at the early stage. Elevated levels of IL-6,IFN-γ,IL-10,C-reactive protein and ferritin are helpful for the diagnosis of CRS.更多还原