CAR-T cell therapy followed by unrelated cord blood transplantation for the treatment of relapsed/refractory B-cell ALL in children and young adults: superior survival but relatively high posttransplant relapse

Abstract Background Several studies have indicated that chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation is beneficial for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Whether consolidative unrelated cord blood transplantation (UCBT) is suitable in R/R B-ALL after CAR-T therapy remain uncertain. Objective We aimed to assess the efficacy and safety of CAR-T therapy before UCBT for children and young adults R/R B-ALL patients. Study design : We retrospectively analyzed 43 R/R B-ALL and under 18 years patients who underwent single-unit UCBT at the First Affiliated Hospital of University of Science and Technology of China (USTC) between February 2012 and November 2020. Among them, 21 patients achieved complete remission (CR) following CAR-T therapy before UCBT (the CAR-T group), and the remaining 22 patients remained non-remission (NR) without prior CAR-T therapy before UCBT (the NR group). The clinical outcomes between two groups were analyzed. Results : The median time from CAR-T therapy to UCBT was 62 (range,42 to 185) days. There were no significant differences in the incidences of grade II-IV, III-IV acute graft-versus-host disease (GVHD) and 2-year extensive chronic GVHD between the two groups. Compared with the NR group, a lower 2-year cumulative incidence of transplant-related mortality and higher probabilities of 2-year overall survival, leukemia-free survival, and GVHD-free relapse-free survival were found in the CAR-T group (P = 0.037, 0.005, 0.028 and 0.017, respectively). However, the 2-year cumulative incidence of relapse (CIR) was comparably high between two groups (26.7% in the CAR-T group and 38.3% in the NR group, P = 0.41). In the CAR-T group, patients with minimal residual disease (MRD) positive before UCBT had a high CIR comparing with those with MRD negative before UCBT (66.7% vs.19.2%, P = 0.006). Conclusion : CAR-T therapy followed by UCBT produces superior survival in R/R B-ALL, but treated patients still exhibit a high posttransplant relapse rate.