Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future

Abstract

beta-Thalassemia major and sickle cell disease (SCD) are among the most common hereditary disorders worldwide. The supportive treatment of beta-thalassemia major requires chronic, life-long RBC transfusions, which cause progressive iron overload and the potential for impaired endocrine, cardiac and hepatic function. The phenotype of thalassemia major is reliably predicted by its genotype. In contrast, SCD is a variable genetic disease caused by a single amino acid substitution in the beta chain of human hemoglobin. Manifestations of SCD are quite varied, but generally result from the tendency of Hb S to irreversibly polymerize under physiologic stressors such as hypoxemia and acidosis. The polymerization causes perturbations in the erythrocyte integrity that promote vaso-occlusion and which manifest as clinical events such as severe painful episodes, acute chest syndrome, splenic infarction, stroke and avascular necrosis of target joints. The only cure proved for these disorders is correction of the genetic defect by allogeneic hematopoietic cell transplantation (HCT). We illustrate the pediatric experience of HCT for hemoglobinopathies and discuss how these results affect future therapeutic decisions in children who inherit these disorders.