matched sibling bone marrow transplantation results in approximately 85% event free survival in high-risk patients with Sickle Cell Disease (SCD) (Walters, NEJM, 2006). However, this approach is limited by 5-10% transplantrelated mortality, 5-10% primary graft failure and the late effects of Bu/CY. Alternate approaches include reduced toxicity but more immunosuppressive conditioning and the use of sibling cord blood (Geyer/Cairo, BJH, 2011 and Freed/ Cairo, BMT, 2012). Objective: To determine the safety, donor chimerism and long term organ function associated with Bu 12.8-16 mg/kg, fludarabine180 mg/m 2 and alemtuzumab 54 mg/m 2 (BFA) reduced toxicity conditioning (RTC) prior to HLA-matched sibling donor transplantation in pediatric recipients with high risk SCD. Methods: Patients 21 years of age with HbSS, HbSC, HbSb + or HbSb 0 were eligible if highly symptomatic (such as 2 vaso-occlusive crises per year requiring narcotics, acute chest syndrome, stroke, retinopathy, splenic sequestration) and with an HLA-matched sibling donor. Conditioning consisted of busulfan (4mg/kg x 4d < 4 yrs and 12.8mg/ kg x 4d > 4 yrs), fludarabine (30mg/m 2 x 6d), and alemtuzumab (2mg/ m 2 x 1d, 6mg/m 2 x 2d, and 20mg/m 2 x 2d) as we have described (Styczynski/Cairo,BMT,2011). All received tacrolimus and MMF as GVHD prophylaxis as we have described (Bhatia/Cairo, BBMT, 2010). Results: 12 patients (11M:1F), median age 12 (2-19) with symptomatic SCD underwent sibling BM (n¼10) or CB (n¼2) Allogeneic Stem Cell Transplantation (AlloSCT). Median follow-up was 33 months. Median time to neutrophil and platelet engraftment for recipients of sibling BM and CB were 16 days (13-18), 18.5 days (9-43) and 39.5 days (38-41) and 74 days (73-75), respectively. The probability of grade II-IV and grade III-IV aGVHD were 16.7% and 8.3%. No patients developed cGVHD. Patients achieved mean whole-blood donor chimerism of 85, 94, 93, 93, 89 and 93% and mean erythroid (CD71) donor chimerism of 89, 89, 93, 90, 86, and 94% at days 30, 60, 100, 180, 365 and 730 post-transplant, respectively. The Kaplan-Meier probability of OS and EFS was 100% (CI 95 : 73.5-100%). Neurological, pulmonary, vascular, and splenic function were stable to improved at 2 years. Conclusions: BFA (RTC) and HLA-matched sibling bone marrow and cord blood AlloSCT in pediatric recipients results in excellent EFS, long term donor chimerism, and stable/improved organ function.