Update of the decision-making algorithm on selecting transfusion-dependent β-thalassemic patients for gene therapy...

β-thalassemia is a globally distributed hereditary red blood cell disorder. Up to now, clinical management of transfusion-dependent β-thalassemia (TDT) patients is still based on chronic transfusion combined with iron chelation therapy. Allogeneic hematopoietic cell transplantation potentially provides a cure, but few patients have an HLA-identical sibling, and optimal results are reported in patients ≤ 14 years. The European Hematology Association (EHA), through the EHA Scientific Working Group on Red Cells/Iron and the European Bone Marrow Transplantation (EBMT) group, has updated a 2021 EHA decision-making algorithm on evidence and expert consensus with the aim of identifying which patients with TDT could benefit from gene therapy (GT). Indeed, it is important to establish the patient setting for whom it is a priority, particularly in the early phase of real-world use outside experimental trials. Moreover, actual price, limited availability, and resource disposal constitute a further indication of a rational and progressive approach to this innovative treatment. In this expert consensus document, different clinical scenarios have been considered and analyzed for the possible impact on treatment outcome. This expert opinion provides dynamic, updatable, priority-based guidance for physicians taking care of TDT patients.