Date of Award

January 2013

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Mitchell S. Cairo

Second Advisor

Farzana Pashankar

Subject Area(s)

Medicine

Abstract

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.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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