Nonmyeloablative matched sibling stem cell transplantation with the optional reinforced stem cell infusion for patients with hemoglobinopathies.

BACKGROUND The NIH protocol for nonmyeloablative (NMA) conditioning allogeneic stem cell transplantation (alloSCT) with alemtuzumab and low-dose total body irradiation corrected the abnormal sickle cell disease (SCD) phenotype without the risk of graft-versus-host disease. AlloSCT using NMA conditioning had been rarely applied to β-thalassemia major (β-TM) patients. METHODS To avoid prolonged immunosuppression, we developed a two-stage strategy. Mixed donor chimerism was initially achieved using the protocol developed by the NIH. Thereafter, we facilitated donor chimerism using the optional reinforced stem cell (SC) infusion in cases requiring protracted immuno-suppression or experiencing impeding graft failure. RESULTS In this study, β-TM (n=9) and SCD (n=4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four β-TM, achieved stable mixed chimerism without receiving optional reinforced SC infusion. All patients that received optional reinforced infusion recipients achieved complete (n=4) or mixed chimerism (n=1). The overall survival rate and event-free survival at 4 years of 91.7% (95% CI; 53.9-98.8) in both groups, with a thalassemia-free survival rate in β-TM patients of 87.5% (95% CI; 38.7-98.1). CONCLUSION This study is the first to report successful NMA conditioning alloSCT to achieve stable mixed chimerism correcting the abnormal hemoglobin phenotype in adult β-TM patients.