Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
Shanghai Genbase Biotechnology Co., Ltd., Shanghai, China.
Cell Transplant. 2023 Jan-Dec;32:9636897231158155. doi: 10.1177/09636897231158155.
Maintaining the efficacy of anti-CD19 chimeric antigen receptor modified (CAR) T-cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) is an urgent problem. In this study, we aimed to compare the efficacy of donor hematopoietic stem cell infusion (DSI) therapy and donor lymphocyte infusion (DLI) therapy as a maintenance therapy after R/R B-ALL patients achieved CR in anti-CD19-CAR T-cell therapy but relapsed after allo-HSCT. In total, 22 B-ALL patients who relapsed after allo-HSCT received anti-CD19-CAR T-cell therapy. Patients who responded to CAR T-cell therapy received DSI or DLI as maintenance therapy. We compared the clinical responses, acute graft versus host disease (aGVHD), expansion of CAR-T-cells, and adverse events between the two groups. In our study, 19 patients received DSI/DLI as maintenance therapy. After DSI/DLI therapy, progression-free survival and overall survival were higher in the DSI group than in the DLI group at 365 days. The grades I and II of aGVHD was observed in four patients (36.4%) in the DSI group. Only one patient developed grade II aGVHD in the DLI group. The peaks of CAR T-cells in the DSI group were higher than those in the DLI group. IL-6 and TNF-α levels increased again in nine of 11 patients after DSI but not in the DLI group. Our findings indicate that for B-ALL patients who relapse after allo-HSCT, DSI is a feasible maintenance therapy if CR is obtained with CAR-T-cell therapy.
维持抗 CD19 嵌合抗原受体修饰(CAR)T 细胞疗法在异基因造血干细胞移植(allo-HSCT)后复发的 B 细胞急性淋巴细胞白血病(B-ALL)患者中的疗效是一个亟待解决的问题。在这项研究中,我们旨在比较供体造血干细胞输注(DSI)治疗和供体淋巴细胞输注(DLI)治疗作为抗 CD19-CAR T 细胞治疗后达到完全缓解(CR)但 allo-HSCT 后复发的 R/R B-ALL 患者维持治疗的疗效。共有 22 例 allo-HSCT 后复发的 B-ALL 患者接受了抗 CD19-CAR T 细胞治疗。对 CAR T 细胞治疗有反应的患者接受 DSI 或 DLI 作为维持治疗。我们比较了两组患者的临床反应、急性移植物抗宿主病(aGVHD)、CAR-T 细胞扩增和不良事件。在我们的研究中,19 例患者接受了 DSI/DLI 作为维持治疗。在 DSI/DLI 治疗后,DSI 组的无进展生存期和总生存期在 365 天时均高于 DLI 组。DSI 组有 4 例(36.4%)患者发生 I-II 级 aGVHD,DLI 组仅 1 例患者发生 II 级 aGVHD。DSI 组的 CAR-T 细胞峰值高于 DLI 组。11 例患者中有 9 例在 DSI 后再次出现 IL-6 和 TNF-α水平升高,但 DLI 组没有。我们的研究结果表明,对于 allo-HSCT 后复发的 B-ALL 患者,如果 CAR-T 细胞治疗获得 CR,则 DSI 是一种可行的维持治疗方法。