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Forty patients with high-risk hematologic malignancies, median age 9 years, underwent haploidentical-HSCT from April 2005 to April 2015. Seventeen patients were transplanted with CD3-depleted PBSCs by negative selection (TCD group) following a reduced-intensity conditioning regimen (RIC), and 23 patients received T-cell-replete PBSCs followed by post-transplantation cyclophosphamide (PT-Cy group) after myeloablative conditioning (n = 16) or RIC (n = 7). Outcomes are reported for the TCD and PT-Cy recipients, respectively. Engraftment was achieved in 88% versus 100%. Median time to neutrophils >500/μL was 10 days versus 15 days. Platelets >20 000/μL occurred at a median of 16 days versus 20 days, respectively. Transplant-related mortality (TRM) was 24% versus 26% at 1 year. The cumulative incidence (CI) of grade III - IV acute GvHD was 7% versus 5%, and chronic GvHD 9% versus 53% (P = 0.029). Relapse at 2 years was 31% versus 24%. Actuarial overall survival rates at 2 years were 47% versus 48%. Causes of death were infections (n = 3), sinusoidal obstructive syndrome (n = 4), acute GvHD (n = 2) and relapse (n = 9). These results indicate that haploidentical-HSCT is feasible in Uruguay. The TRM rate is of concern and should be the focus of continuing attention. Chronic GvHD risk was higher in the PT-Cy approach, so modifications are justified.