Outcome of second allogeneic hematopoietic cell transplantation in adult patients with relapsed B-cell acute lymphoblastic leukemia in the era of new immunotherapeutic agents.

Allogeneic hematopoietic cell transplantation (allo-HCT) is still recommended as a standard treatment of choice for relapsed B-cell acute lymphoblastic leukemia (ALL). Regarding the second allo-HCT (allo-HCT2), variable comorbid conditions and leukemic evolution after previous allo-HCT may affect poor survival outcomes. With the introduction of newer immunotherapeutic agents including blinatumomab, inotuzumab ozogamicin, and ponatinib, we got more chances for allo-HCT2 expecting more promising transplantation outcomes. We analyzed 78 adult patients with post-HCT relapsed B-ALL undergoing allo-HCT2. Philadelphia chromosome (Ph)-negative B-ALL (n = 45) treated with nower agents showed improved survival outcomes compared to conventional chemotherapy (median survival 29.6 vs. 6.8 months, p = 0.018), which was primarily driven by lower 5-year cumulative incidence of relapse (37.9% vs. 68.8%, p = 0.037). In contrast, no survival advantage of allo-HCT2 was observed in Ph-positive B-ALL (n = 33) with a median survival of 16.0 months across the salvage regimens. Our findings highlighted the efficacy of newer salvage therapies in Ph-negative B-ALL, while underscores the need for alternative strategies for Ph-positive ALL. Overall, relapses after allo-HCT2 are still challenging which emphasize the need for strategies other than allo-HCT3 including newer agents such as chimeric antigen receptor (CAR)-T/NK therapies or post-transplant minimal residual disease targeted therapies.