Comparison of the Efficacy and Adverse Effects of Recipient-Derived Versus Donor-Derived CAR-T Cell Therapy for Post-Transplant Relapse in B-ALL

Background Chimeric Antigen Receptor T (CAR-T) cells have been demonstrated to be an effective treatment for relapsed acute B-cell lymphoblastic leukemia (B-ALL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells for CAR-T therapy can be derived from the patient's own peripheral blood (recipient) or from the donor's peripheral blood. Despite having identical genomes, the different maturation environments of these T cells can lead to functional differences. This study aims to compare the clinical outcomes of CAR-T cells derived from these two sources. Methods This multicenter, retrospective cohort study collected clinical data from 36 patients who experienced B-ALL relapse after allo-HSCT and received CD19 CAR-T cell therapy between January 2016 and October 2023 across seven centers. The primary endpoint was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate at 28 days post-CAR-T cell infusion. Secondary endpoints included the 2-year overall survival (OS) rate, 2-year event-free survival (EFS) rate, incidence of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), and CAR-T cell-related encephalopathy syndrome (CRES). Results Retrospective analysis was performed on 36 patients: 12 in the recipient group and 24 in the donor group. The recipient and donor groups showed no significant differences in CR/CRi rates (83.33% vs. 100%, P=0.105), 2-year EFS rates (50.8% vs. 51.6%, P=0.617), and 2-year OS rates (49.5% vs. 63.6%, P=0.215). Additionally, the incidence of GVHD, CRS, and CRES did not significantly differ between the two groups. Further analysis within the donor group revealed 12 matched sibling donors (MSD) and 12 haploidentical donors (HID). The 2-year EFS rate was significantly higher in the HID group compared to the MSD group (75.0% vs. 30.7%, P=0.043), while no significant differences were observed in CR/CRi rates, 2-year OS, and the incidence of GVHD, CRS, and CRES between these subgroups. Conclusion Both recipient-derived and donor-derived CD19 CAR-T cell therapies are effective treatment options for B-ALL relapsed post-allo-HSCT. Haploidentical donor-derived CAR-T cells offer a longer EFS and may be considered the optimal choice.