UCBT offers a cure for thalassemia and has advantages as a stem cell source because the requirement for an HLA match between donor and recipient is less stringent. Previous reports of UCBT for thalassemia have yielded transplant related mortality (TRM) that was quite high and it is known that pre-freeze total nucleated cell (TNC) dose is critical for UCBT. With strategies that maximize TNC dose – using non-red cell reduced but plasma depleted (PD) CB, no post-thaw wash (NW), and double cord transplantation (DCT) when necessary – we have achieved promising results with UCBT in young patients with transfusion-dependent β-thalassemia. Between 10/2003 and 5/2008, 39 CB products were infused after Bu/Cy/ATG myeloablation into 30 pediatric thalassemia major patients (9 DCT) using NW PD CB exclusively. Patient status: 21 Pesaro class−1, 8 Pesaro class−2, and 2 unknown. Median age was 5 years (range 1–14 years) with a median weight of 18 kg (range 11–37 kg). The data was audited by the transplant center (TC) and on-site by CIBMTR (98.5% accuracy for Chang Gung). Median pre-freeze TNC cell dose was 10.9×107/kg, and median pre-freeze CD34+ cell dose was 4.0×105/kg. The number of CB products HLA ABDR matched were 4, 11, and 24 for 6/6, 5/6, and 4/6 or fewer matches. No significant adverse events were observed despite major ABO incompatibility in some cases and forgoing post-thaw wash. Cumulative incidences of donor-derived (determined by chimerism studies) neutrophil (ANC500), platelet 20K and 50K (plt 20K & 50K) engraftment were 96±11%, 92±11% and 92±12%, and median times to ANC500, plt 20K and 50K engraftment were 17.5 days (range 11–26), 49.5 days (range 28–135) and 63.5 days (range 35–203), respectively. Grade III/IV acute GvHD occurred in 40±9%, and extensive chronic GvHD occurred in 4±4% of the patients. Transplant related mortality were 10±5% at 100 days and 13±6% at 1 year. Overall survival at 1 and 3 years were 87±6% and 82±8%, while disease-free survival at 1 and 3 years were 85±7% and 78±9%. Five patients expired including 1 death prior to day +10 due to traumatic head injury. Mean and median follow up times were 24 and 16 months respectively (range 0.3–58 months) as of August 2008. To our knowledge, this is the largest single-institutional UCBT series for thalassemia, and shows the favorable clinical results that are attainable when TNC dose is optimized with PD CBU, no post-thaw wash and DCT when necessary.
Disclosures: Wang:StemCyte: Employment, Equity Ownership. Gjertson:StemCyte: Consultancy. Law:StemCyte: Employment, Equity Ownership. Petz:StemCyte: Employment, Equity Ownership. Chow:StemCyte: Employment, Equity Ownership.