Introduction: DCBT in children with acute leukemia is controversial given the findings of the recent BMT CTN randomized study. However, many children will not have adequate single-units based on the recent CIBMTR analysis (cryopreserved TNC > 3.0 x 107/kg and 6-8/8 allele donor-recipient HLA-match). Methods: We analyzed 35 consecutive pediatric DCBT patients (pts) treated for acute leukemia (10/2005-2/2013). All CBT recipients in this period received 2 units. Results: Median pt age was 7.5 yrs (range 0.8-18), median weight was 28 kg (range 8-75), and 69% had non-European ancestry. Seventeen pts had AML: 6 CR1 (one each with M7, secondary 5q- MDS, FLT-3 ITD, Ph+, Down syndrome MRD+, germline mutation CEBPa), 8 CR2 (one MLL MRD+), 1 CR3, and 2 in aplasia. Seventeen pts had ALL: 10 CR1 [3 Ph+ (one MRD+), 2 T-cell ALL, 1 MLL, 1 L3 disease, and 3 multiple inductions], 4 CR2, 3 CR3. One pt had advanced CML. Conditioning was Cy120/Flu/TBI1375 (N = 21, 60%) or chemotherapy-only (N = 14, 40%, 10 Clo/Mel/Thio, 4 Bu/Mel/Thio). GVHD prophylaxis was CNI/ MMF. Units had a high degree of donor-recipient HLA-allele disparity (Table). The cumulative incidence of sustained donor neutrophil engraftment was 94% (95%CI:78-98, median 21 days, range 12-33), and hematopoiesis was mediated by a single unit. Day +180 platelet engraftment ≥ 50 x 109/l was 82% (95%CI: 64-92, median 51 days, range 39-299). CD4+ count recovery was prompt: mean day 60 201 (SD:+/-180), and day 120 250 (SD:+/-150). Of 33 engrafted pts, 10 (30%) engrafted with a unit with pre-cryopreservation TNC < 2.5 x 107/kg, and 17 (51%) engrafted with a unit ≤ 5/8 HLA-allele matched. The cumulative incidence of day 100 grade II-IV acute GVHD was 46% (95%CI:29-61), and 23% (95%CI:11-38) had grade III-IV acute GVHD. 3-year chronic GVHD was 14% (95%CI:5-28). With a median 58 month (range 20-105) follow-up, the 3-year cumulative incidence of TRM was 11% (95%CI:4-24); deaths were due to graft failure (2), HHV-6 encephalitis (1), and viral pneumonia (1). Relapse at 3-years was 20% (95%CI:9-35): 2 AML CR1 (one FLT-3 ITD, one M7), one previously refractory AML, and 4 ALL (2 CR1, 1 CR2, 1 CR3). None of the 4 pts transplanted with MRD+ relapsed. Three-year DFS was 68% (95%CI:50-81), with no difference based on diagnosis (p = 0.25, Figure), TBI-based cytoreduction (p = 0.68), or non-European ancestry (p = 0.24). Conclusions: Despite high-risk disease and grafts with a very high degree of donor-recipient HLA-allele mismatch, the low TRM and relapse rates after pediatric DCBT are striking, with either TBI-based or chemotherapy-only conditioning. Although young children could have adequate single-unit grafts, a significant percentage will not. Therefore, DCBT remains an important consideration, especially for children of ethnic minorities.