Curative Approach to the Treatment of Beta-Thalassemia and Sickle Cell Disease with Hematopoietic Stem Cell...

β-thalassemia and sickle cell disease are two inherited hematological diseases due to defective hemoglobin synthesis or to the production of hemoglobin with altered properties. These two conditions have prolonged survival with modern support therapies, albeit life-long, complex, expensive and resource-consuming. Studies carried out in the last three decades have shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) and gene therapy may offer a curative approach for these diseases. Allo-HSCT should be performed early in life to reduce disease-related complications like irreversible tissue damage due to iron overload in patients with transfusion-dependent β-thalassemia (TDT) and systemic vasculopathy in patients with sickle cell disease (SCD). HSCTs from a matched-sibling donor or a matched-unrelated donor represent the best therapeutic option; however, haploidentical HSCT in both TDT and SCD is now increasingly performed as a valuable and viable option for a larger number of these patients. An alternative curative strategy is based on gene therapy. These curative approaches, particularly those of gene therapy, are available only in a part of the world. Gene therapy diffusion is strongly limited by its high technological and infrastructure requirements and its very high cost. Criteria must be defined for the optimal selection of TDT and SCD patients for allo-HSCT or gene therapy.