Objective: To study the long-term efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed patients with B-cell acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods: A total of 7 patients with B-cell ALL relapsed after allo-HSCT were treated with CD19 CAR-T cells from September 2015 to March 2018. Among them, 6 had hematological recurrence and 1 had positive of MRD. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 6.0 (range 4.0-8.6) )×106/kg. Long-term efficacy and toxicity were evaluated.
Results: Bone marrow examination performed at d 30 after CAR-T infusion showed that all 7 patients achieved complete remission and MRD negative, grade I CRS for 1 case and grade II CRS for 6 cases, two of them had mild neurotoxicity, which was controlled by treatment. Two patients presented grade VI intestinal GVHD after CAR-T infusion. The median follow-up time was 18 months (range 12-42). Follow-up showed that two patients relapsed at 9 months and 14 months after treatment, out of 2 patients one died of progressive disease and the other reachived the hematological remission, but MRD was positive after CD22 CAR-T cell therapy. At present, five patients are disease-free survival, moreover showed complete donor chimerism. One year after CAR-T cell therapy, the results of immune reconstitution showed that CD4 level was more than 300×106/L in 5 patients who disease-free survived. Among them, 3 patients had poor recovery of immunoglobulin and received gamma globulin replacement therapy.
Conclusion: All patients are followed up for at least one year. The preliminary efficacy and safety are satisfactory. CAR-T cell infusion is an effective method for the treatment of B-ALL recurrence after allo-HSCT.
题目: CD19嵌合抗原受体T细胞治疗急性淋巴细胞白血病患者接受移植后复发的疗效.
目的: 研究CD19 嵌合抗原受体T细胞(CAR-T)治疗B细胞急性淋巴细胞白血病（ALL）异基因造血干细胞移植（allo-HSCT）后，复发患者的长期疗效和安全性.
方法: 对2015年9月至2018年3月期间7例B细胞ALL接受allo-HSCT后复发患者（血液学复发6例，免疫残留阳性1例）应用CD19 CAR-T细胞治疗，均是输注1次针对CD19抗原CAR-T细胞治疗，输前常规予以FC方案，CAR-T细胞中位数为6.0（4.0-8.6)×106/kg，评价其长期疗效和毒副作用.
结果: 输注后d 30对患者进行骨髓检查，7例患者均取得完全缓解和MRD-，1例Ⅰ级CRS，6例Ⅱ级CRS，6例中2例发生轻度神经毒性，经治疗控制；2例患者输注后发生急性Ⅵ度肠道GVHD，中位随访时间18 (12-42)个月；2例分别在治疗后9和14个月复发，其中1例患者因病情进展死亡，另1例患者接受CD22 CAR-T细胞治疗后获得血液学缓解，但是MRD+。现无病存活患者5例，经植入分析为完全供者嵌合体。CAR-T细胞治疗后1年无病存活的5例患者淋巴细胞CD4在300×106/L以上，其中的3例免疫球蛋白恢复不良，丙种球蛋白替代治疗.
结论: 随访1年以上时间，其初步疗效及安全性令人较为满意，CAR-T细胞是治疗allo-HSCT后复发的B细胞ALL有效手段.