HSCT remains the only cure for patients with transfusion-dependent thalassemia until gene therapy strategies are proven to be safe

Abstract

Patients with β-thalassemia suffer from severe anemia, iron overload and multiple complications, that affect their quality of life and well-being. Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling donor, performed in childhood, has been the gold standard for thalassemic patients for decades. Unfortunately, siblings are available only for the minority of patients. Fully matched unrelated donors have been the second choice for cure, with equal results as far as overall survival is concerned, having though the cost of frequent and serious complications. On the other hand, haploidentical transplantation is performed more frequently during the last decade, with promising results. Gene therapy represents a novel therapeutic approach, with impressive results from clinical trials, both from gene addition strategies, as well as from the emerging gene editing tools. After reviewing current critical points of HSCT using alternative donors and assessing recently reported safety issues of gene therapy methods, we conclude that, although a breakthrough, the safety of gene therapy remains to be established.