6556 Background: The feasibility and outcomes of bridging relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) patients to allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T therapy require further investigation. This study evaluated long-term outcomes and prognostic factors in this setting. Methods: We conducted a retrospective analysis of 300 consecutive R/R B-lineage leukemia patients (295 B-ALL, 98.3%) who underwent allo-HSCT after CAR-T therapy. Somatic mutation screening via next-generation sequencing was performed on 179 patients. Univariate Cox regression analyzed factors associated with transplant outcomes. A contemporaneous cohort of 36 transplanted patients without prior CAR-T served as a comparator. Results: Median age at transplant was 14 years (range, 1-68). Prior to HSCT, 220 (73.3%), 75 (25.0%), and 5 (1.7%) patients received CD19-, CD22-, and Mix-CAR-T, respectively; 265 (88.3%) achieved complete remission (CR), and 39 (13.0%) were minimal residual disease (MRD)-positive. The 3-year disease-free survival (DFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) for the CAR-T bridging cohort were 64.0% (95%CI, 58.6-69.8%), 74.5% (95%CI, 69.5-79.9%), 28.4% (95%CI, 23.6-34.1%), and 7.6% (95%CI, 5.04-11.3%), respectively. Outcomes did not differ significantly from the non-CAR-T cohort (OS, p=0.54; DFS, p=0.24). Failure to achieve CR pre-HSCT (HR=3.31, p<0.0001) and MRD-positivity (HR=3.69, p<0.0001) were risk factors for relapse, while chronic graft-versus-host disease was protective (HR=0.35, p=0.0002). Pre-HSCT MRD-positivity, fungal infection, and viral cystitis increased NRM risk. TP53 (15.1%), KMT2D (14.5%), NRAS (14.0%), KRAS (13.4%), and ABL1 (9.5%) were the most frequently mutated genes. TP53 mutation was a significant risk factor for inferior DFS (HR=3.37, p<0.0001) and OS (HR=3.56, p<0.0001). GNAS and KDM6A mutations predicted higher CIR, while ETV6 mutation was associated with increased NRM. Conclusions: Bridging to allo-HSCT after CAR-T therapy is a feasible and effective strategy for R/R B-ALL, providing substantial long-term survival. Achieving pre-transplant CR and MRD-negative status is critical for outcome. Somatic mutations, particularly TP53, hold significant prognostic value, aiding in risk stratification and treatment optimization for these patients.
Li et al. (Wed,) studied this question.