Relapse remains a key cause of transplant failure in high-risk B-cell acute lymphoblastic leukemia (B-ALL). Nevertheless, the available maintenance therapy for relapse prevention after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in high-risk B-ALL, especially in Ph-negative B-ALL patients, has limitations and suboptimal efficacy. Notably, donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has emerged as a successful salvage or preemptive strategy in B-ALL patients following allo-HSCT [1,2,3]. In light of these developments, prophylactic CAR-T cell infusion after allo-HSCT may be a potential strategy to eliminate residual leukemia cells in high-risk B-ALL patients, thereby reducing the risk of relapse prior to the complete immune reconstitution. In this study, we found that prophylactic infusion of CAR-T cells after allo-HSCT in high-risk B-ALL patients resulted in acceptable adverse events and a significantly reduced relapse rate.