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INTRODUCTION Acute leukemia relapsing after allogeneic stem cell transplantation (AlloSCT) is usually associated with dismal prognosis. Treatment options in this population remain limited. We evaluated the outcomes of second AlloSCT in patients with acute leukemia relapsed after previous AlloSCT in centers from Grupo Argentino de Trasplante de Médula Ósea (GATMO) METHODS AND RESULTS We carried out a retrospective analysis in 21 adult patients who received a second transplant as a salvage treatment for relapsed acute leukemia. Main outcomes were overall survival (OS) and leukemia free survival (LFS). Variables evaluated were re-induction chemotherapy regimen, conditioning regimen, donor type, early immunosuppression tapering, and the use of maintenance treatment. Mean age was 28 years old (range 16-53). Thirteen were under 30 years, 11 were women, 16 were acute myeloid leukemia. Median time from the first transplant to the relapse was 16,3 months (range 2 to 91 moths). Fourteen patients were MRD negative at the time of second AlloSCT (4 of them in aplasia) and 7 were either positive MRD or refractory disease. Almost all patients received a different re-induction chemotherapy regimen as well as a different conditioning compared to the first transplant. Sixteen out of 21 patients were transplanted with a different donor. Patients without graft versus host disease (GVHD) at day 100 started immunosuppression tapering. Considering the 16 patients alive/relapse free at day 100, half of them received maintenance therapy (6 azacitidine, one sorafenib and one dasatinib). With a median follow up of 24 months, 1-year OS and LFS was 62% and 38%. Age was a strong predictor of survival. There were no patients ≥30 years alive or relapse free beyond 6 months of the procedure, while LFS at 2 years was 58% (8/13) in patients younger than 30 years (p=0.0007). One year LFS was 60% for patients receiving any type of maintenance, compared to 33% of patients who did not receive maintenance (p=0.2). There were no differences in changing the donor or the pre-transplant status. CONCLUSION Second AlloSCT for relapsed acute leukemia is a potential curative option. Younger patients showed better outcomes. Patients relapsing after 6 months could have better prognosis. Maintenance treatment after second transplant should be evaluated, however prospective studies are needed in this scenario to draw better conclusions. Figure. Figure. No relevant conflicts of interest to declare.