【摘要】 难治急性淋巴细胞白血病病死率极高,CAR-T细胞免疫治疗为此提供新的选择。本文介绍1例CD19CAR-T细胞治疗缓解后短期复发的TP53突变阳性难治急性B淋巴细胞白血病,经CD22 CAR-T联合单倍体异基因造血干细胞移植治疗成功的病例。本研究采用流式细胞术观察患者CD19 CAR-T细胞和CD22 CAR-T细胞两次治疗的外周血CAR-T细胞比例,PCR法检测CAR基因表达;临床观察患者2次CAR-T细胞治疗过程中的疗效和不良反应。结果显示,CD19 CAR-T和CD22 CAR-T细胞2次治疗均于第14天达到骨髓完全缓解,且不良反应轻微。但CD19 CAR-T细胞治疗缓解后2周骨髓复发,患者外周血检测到异常19 CAR基因表达,同时TP53突变水平亦增高。最终CD22 CAR-T细胞挽救治疗桥接单倍体造血干细胞移植后成功。由此表明在细胞制备过程中应进一步提高CD3+细胞纯度;CD22 CAR-T治疗可以作为CD19 CAR-T治疗复发的一个挽救治疗措施。更多还原

【Abstract】 The mortality rate of the acute lymphocyte disease is extremely high, and CAR-T cell immunotherapyprovides a new choice. This paper introduced a refractory acute B-lymphoblastic leukemia(B-ALL) patient with TP53 positive mutation and short-term recurrence after remission from CD19 CAR-T therapy. The case was successfully treatedby CD22 CAR-T combined with allogeneic hematopoietic stem cell transplantation. The proportions of peripheral bloodCD19 CAR-T and CD22 CAR-T cells were analyzed by flow cytometry. The expression of CAR gene in peripheral blood wasdetected by PCR method. The efficacy and the side effects of CD19 CAR-T and CD22 CAR-T therapy were observed in thispatient. The CD19 CAR-T and CD22 CAR-T cell treatments both achieved complete remission on the day 14, and the sideeffects were minor. But bone marrow recurrence 2 weeks after remission from CD19 CAR-T cell therapy with abnormal 19CAR gene expression in peripheral blood and increased TP53 mutation level. The patient was successfully treated with CD22 CAR-T cells bridged with haploid hematopoietic stem cell transplantation therapy. In a word, the purity of CD3+cells shouldbe further improved in the process of CAR-T cell manufacture. CD22 CAR-T therapy could be used as a salvage measuresfor the patient with relapse of CD19 CAR-T therapy.更多还原