Abstract : Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has ă been proposed to increase the cell dose. We report a prospective ă randomized study, designed to compare single-vs double-UCB ă transplantation in children and young adults with acute leukemia in ă remission or myelodysplasia. Eligible patients had at least two 4-6 ă HLA-identical UCBs with >3x10(7) nucleated cells/kg for the first and ă >1.5x10(7) for the second. The primary end point was the 2-year ă cumulative incidence of transplantation strategy failure, a composite ă end point including transplant-related mortality (TRM), engraftment ă failure, and autologous recovery. Randomized patients who did not ă proceed to transplantation due to refractory disease were considered ă transplantation failures. A total of 151 patients were randomized and ă included in the intent-to-treat analysis; 137 were transplanted. ă Double-UCB transplantation did not decrease transplantation strategy ă failure (23.4% 6 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant ă survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% ă +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation ă compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% ă after double-unit transplantation. The final relapse risk did not ă significantly differ, but relapses were delayed after double-unit ă transplantation. Overall incidences of graft-versus-host disease (GVHD) ă were similar, but chronic GVHD was more frequently extensive after ă double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, ă P=.02). In an exploratory subgroup analysis, we found a significantly ă lower relapse risk after double-unit transplantation in patients ă receiving total body irradiation without antithymocyte globulin (ATG), ă whereas the relapse risk was similar in the group treated with busulfan, ă cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell ă dose remains the standard of care and leads to low TRM. Double-unit ă transplantation should be reserved for patients who lack such units. ă This trial was registered at www. clinicaltrials. gov as #NCT01067300.