CAR-T Versus Non-CAR-T Bridging Strategies Before Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Systematic Review.

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) remains a major therapeutic challenge despite recent advances in immunotherapy. Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising bridging strategy to allogeneic hematopoietic stem cell transplantation (allo-HSCT), although its impact on post-transplant outcomes compared with non-CAR-T bridging strategies remains uncertain. This systematic review compared CAR-T-based with non-CAR-T bridging strategies before allo-HSCT in patients with R/R B-ALL or persistent/recurrent measurable residual disease (MRD) during first complete remission (CR1). PubMed/MEDLINE and Scopus were searched from database inception to August 18, 2026. Eligible comparative studies reported post-transplant outcomes according to the pre-transplant bridging strategy. Two reviewers independently screened the studies, extracted data, and assessed methodological quality using the appropriate Joanna Briggs Institute (JBI) critical appraisal tools. Given the substantial clinical and methodological heterogeneity, a narrative synthesis was performed rather than a meta-analysis. Of 1,957 records identified, 10 comparative reports met the eligibility criteria. Potential patient-level overlap could not be excluded between two reports from the same institution, and all included studies were conducted at single-center institutions in China. CAR-T-based bridging produced deep pre-transplant remissions, but no consistent advantage over non-CAR-T strategies in achieving MRD negativity was observed. One study reported a significantly lower cumulative incidence of relapse (CIR) and higher disease-free survival (DFS) after CAR-T bridging (18.9% vs. 42.2%, p = 0.02; 82.5% vs. 53.7%, p = 0.01), with CAR-T remaining independently associated with a reduced risk of relapse in multivariable analysis. A significant unadjusted overall survival (OS) advantage favoring CAR-T was observed in one small pediatric cohort (84.6% vs. 40.0%, p = 0.008), although potential overlap with another included cohort limits the independent interpretation of this finding. In the largest cohort, CAR-T bridging was independently associated with improved OS in multivariable analysis (hazard ratio = 0.365, 95% CI 0.154-0.857, p = 0.025), despite a nonsignificant unadjusted OS comparison and significantly lower leukemia-free survival (LFS). Across the remaining studies, OS did not differ significantly between bridging strategies, including in two studies comparing CAR-T with blinatumomab. Non-relapse mortality (NRM), hematopoietic engraftment, graft-versus-host disease (GVHD), infectious complications, and endothelial toxicity showed no consistent direction of effect across studies, although delayed platelet recovery and increased viral reactivation emerged as potential safety signals in specific cohorts, particularly following dual-target CD19/CD22 CAR-T therapy. Overall, CAR-T-based bridging before allo-HSCT may improve disease control in selected patients with R/R B-ALL, but the expanded evidence base does not demonstrate a consistent survival or safety advantage over non-CAR-T bridging strategies. The choice of bridging strategy should therefore be individualized according to MRD status, disease biology, CAR-T construct, and transplant eligibility. Prospective multicenter comparative studies are needed to define the optimal sequencing of CAR-T therapy, alternative immunotherapies, and allo-HSCT.