Pre-Transplant MRD Negativity and Age Under 40 Predict Superior Long-Term Survival in Relapsed/Refractory B-ALL After CAR-T Therapy Bridging to Haploidentical HSCT: A Multicenter Retrospective Study With 6-Year Follow-Up.

Sequential allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical approach to enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). The long-term survival rates following allo-HSCT after CAR-T cell therapy remain controversial. We previously reported the results of 122 patients with R/R B-ALL who achieved minimal residual disease negative (MRD-) complete remission (CR) after anti-CD19 CAR-T, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haplo-HSCT (transplant group). Here, we present the extended follow-up of this cohort, with a median of 72.9 months. Compared with the non-transplant group, transplantation recipients had a higher 5-year LFS (50.5% vs. 25.7%; p < 0.001) and OS (53.5% vs. 25.6%; p < 0.001). Multivariable analysis identified MRD positivity at transplantation as an independent factor associated with worse LFS, OS, and a higher cumulative incidence rate of relapse (CIR). MRD-negative patients before transplant (MRD- group) had a lower 5-year CIR compared to MRD-positive patients (MRD+ group) (20.8% vs. 50.0%; p = 0.014). The 5-year LFS rates in the MRD+ and MRD- groups were 26.7% and 59.4%, respectively (p = 0.003). The 5-year OS of the MRD- group was higher than that of the MRD+ group (62.0% vs. 30.5%; p = 0.006). For patients who achieve CR after CAR-T therapy, haplo-HSCT with pre-transplant MRD negativity was associated with better long-term survival. However, infections emerged as a significant complication that may reduce the long-term survival benefits. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1900023957.