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Abstract: Abstract Background Relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem-cell transplantation (allo-HSCT), particularly with extramedullary disease (EMD), has a dismal prognosis. The efficacy and durability of allogeneic chimeric antigen receptor T cell (allo-CAR-T) therapy in this setting remain unclear. Methods Fourteen patients with post-transplant relapsed B-ALL received allogeneic anti-CD19 CAR-T cells, including eight with EMD. Clinical responses, survival, CAR-T kinetics, and toxicities were evaluated. Results With a median follow-up of 13.8 months (range, 4.4–52.9 months), the overall complete remission (CR) rate was 92.9% (13/14), with a median duration of remission (DOR) of 12.7 months (range, 3.5–50.3 months). Among patients with EMD, 87.5% (7/8) achieved CR, with a median DOR of 14.7 months (range, 3.5–50.3 months). Of the eight patients with EMD, four were Philadelphia chromosome-positive and received maintenance therapy with tyrosine kinase inhibitors after allo-CAR-T, including dasatinib ( n =1), ponatinib ( n =2), and olverembatinib ( n =1). Median overall survival and event-free survival were not reached in either the overall cohort or EMD subgroup. CAR-T cells persisted in vivo for a median of 5.9 months (range, 1.2–51.6 months). One patient experienced grade 3 cytokine release syndrome and grade 4 immune effector cell-associated neurotoxicity syndrome. One patient developed acute gastrointestinal graft-versus-host disease, followed by chronic graft-versus-host disease involving the skin and lungs. Conclusion Allo-CAR-T therapy induces sustained remissions in patients with post-transplant relapsed B-ALL, including patients with EMD, and may serve as an effective backbone for tailored combination strategies. Trial registration ChiCTR2000036350, registered on August 22, 2020; retrospectively registered.