The value of chimeric antigen receptor-modified donor lymphocyte infusion (CAR-DLI) is unclear in B-cell acute lymphoblastic leukemia (B-ALL), particularly in patients with relapsed diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, 5 B-ALL patients who relapsed after allo-HSCT received CAR-DLI (CAR-DLI group), and the outcome was compared with 27 relapsed B-ALL patients who received DLI therapy (DLI group). The median complete remission duration of CAR-DLI group was significantly (P=0.020) longer when compared with DLI group: 9 months (range, 2-29) versus 3.2 months (range, 0-17.4). Furthermore, patients receiving CAR-DLI showed significant (P=0.049) survival advantage over DLI group, with median overall survival of 12 months (range, 3-29) and 3.7 months (range, 0-65), respectively. Of note, no patient developed acute graft versus host disease in the CAR-DLI group, while incidence of acute graft versus host disease grades I-II and grades III-IV were 2 (7%) and 4 (14.8%) in the DLI group, respectively. In addition, cytokine release syndrome in CAR-DLI group was manageable. Overall, our study demonstrated that CAR-DLI significantly improved the survival of B-ALL patients relapsed after allo-HSCT, thus indicating that CAR-DLI may represent an alternative and more effective therapy for B-ALL patients with relapsed diseases.