摘要
目的:观察以CD19为靶点的嵌合抗原受体T细胞(Chimeric Antigen Receptor T-Cell Immunotherapy,CAR-T)治疗复发难治性急性B淋巴细胞白血病的疗效并文献复习。方法:37岁女性,急性B淋巴细胞白血病多次化疗后复发,合并中枢神经系统白血病,化疗效果差。2016年5月28日在河南中医药大学第二附属医院回输CD19 CAR-T细胞每千克1.0×106个细胞。通过观察回输后的临床症状,评价是否存在细胞因子风暴及神经系统反应;通过检测骨髓象、免疫表型、微小残留病变等评估临床疗效;通过检测体内CD19+细胞比例和T细胞中CAR+细胞比例以及脱氧核糖核酸(DeoxyriboNucleic Acid,DNA)和血中嵌合抗原受体(Chimeric Antigen Receptor,CAR)的拷贝数,探讨CAR-T细胞在体内的作用过程以及患者长期缓解可能存在的原因。结果:CAR-T细胞回输后,白血病微小残留病变始终为阴性,脑脊液中始终未检测到白血病细胞;回输后初期CD19+细胞比例保持比较低的比例,但至第380天CD19+细胞有扩增趋势;DNA和血浆中CAR的拷贝数均在第9天达到高峰。回输后达完全缓解(CR)34个月。结论:CD19 CAR-T细胞是治疗复发难治性急性B淋巴细胞白血病的有效方法,同时对于中枢神经系统白血病的缓解有较好的疗效,但本病长期缓解的机制仍需进一步探讨。
Objective:To observe the efficacy of chimeric antigen receptor-engineered T cells(CAR-T cells)targeting CD19 in the treatment of recurrent refractory acute B lymphoblastic leukemia and to review the literature.Methods:A 37-year-old-female patient,who had recurrence of acute B lymphoblastic leukemia after multiple chemotherapy,and was combined with central nervous system leukemia,showed poor chemotherapy effect.On May 28,2016,1.0×106 CAR-T cells were reinfused in The Second Affiliated Hospital of Henan University of Chinese Medicine.Cytokine Release Syndrome and neurological responses were evaluated by observing the clinical symptoms after returning;Evaluation of clinical efficacy was made by detecting bone marrow cytology examination,immune phenotype and small residual disease;By detecting the proportion of CD19+cells in vivo and the proportion of CAR+cells in T cells,as well as the number of copies of CAR in DNA and blood,the process of the action of CAR-T cells in vivo and the possible causes of longterm remission of patients were explored.Results:After CAR-T cell were transfused,the small residual disease was always negative,and leukemia cells were never detected in cerebrospinal fluid.The proportion of CD19+cells remained a relatively low ratio after returning,but to the day of No.380,CD19+cells had an amplification trend.The number of copies of CAR in DNA and plasma peaked on the 9th day.It was up to 34 months of complete remission(CR)after returning.Conclusion:CD19 CAR-T cells are an effective method for the treatment of recurrent refractory acute B lymphoblastic leukemia,and have a good curative effect on the remission of central nervous system leukemia,but the mechanism of long-term remission of disease still needs to be further discussed in the clinic.
作者
宋亚琳
王志远
效明星
程志
Song Yalin;Wang Zhiyuan;Xiao Mingxing;Cheng Zhi
出处
《中医临床研究》
2020年第12期85-89,共5页
Clinical Journal Of Chinese Medicine
