Date of Award

January 2013

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Mitchell S. Cairo

Second Advisor

Farzana Pashankar

Subject Area(s)



Myeloablative conditioning (MAC) and HLA-matched sibling allogeneic stem cell transplantation in children with sickle cell disease (SCD) is associated with 85% EFS but limited by acute and late effects of MAC and lack of unaffected HLA-matched sibling donors. Alternatives to MAC include reduced toxicity conditioning (RTC); alternatives to lack of sibling donors include utilizing HLA-matched unrelated cord blood donors (UCB). We investigated the safety and efficacy of RTC (busulfan 12.8-16 mg/kg, fludarabine180 mg/m2, alemtuzumab 54 mg/m2) prior to HLA-matched sibling donor transplantation and UCBT in pediatric recipients with SCD. Twenty patients, median age 6 (1-19yr), M/F 18/2, 10 sibling BM, 2 sibling CBT, and 8 UCBT. Mean donor chimerism was 87% and 87% in whole blood and 93% and 89% in RBCs at days +100 and +365, respectively. There were 3 primary and one secondary graft failures, all following UCBT. Two-year EFS and OS for sibling BM/CB vs. UCBT were 100% vs. 50% (p=.0076) and 100% vs. 62.5% (p=.0333), respectively. Neurological, pulmonary, vascular, and splenic function were stable to improved at 2 years. While RTC and HLA-matched sibling BM/CB AlloSCT in pediatric recipients results in excellent EFS and stable/improved organ function, this approach results in significantly inferior outcomes following UCBT.


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