Treating Severe β-Thalassemia
β-thalassemia is an inherited hemoglobinopathy resulting from mutations in the β A-globin gene. The mutations reduce or eliminate β-globin synthesis, causing ineffective erythropoiesis, chronic hemolysis, and severe anemia. Patients with the most severe disease, “transfusion-dependent β-thalassemia,” need long-term red-cell transfusions and iron chelation for survival. A novel treatment option is gene therapy using a Lentivirus vector.
A multi-center, phase 1-2 study evaluatedthe efficacy and safety of gene therapy in 22 patients, 12 to 35 years old, with transfusion-dependent β-thalassemia. The procedure involved harvesting autologous CD34+ hematopoetic stem cells, and ex vivo transduction with the LentiGlobin vector containing a functional β-globin gene, followed by myeloablation and re-infusionof the treated stem cells. The patients were followed for a median of 26 months after infusion. In the 13 patients who originally had reduced β-globin synthesis, 12 achieved normal hemoglobin levels and had no need for red-cell transfusions during the followup period.
The 9 patients who originally had no β-globin synthesis had reductions in the median number and volume of transfusions needed; and 3 of the 9 needed no red-cell transfusions during the followup period. Treatment-related adverse events included hematologic alterations resulting from myeloablation, as well as 2 episodes of venoocclusive liver disease, which resolved. No replication-competent Lentivirus was detected. The authors concluded that LentiGlobin gene therapy may reduce or eliminate the need for long-term red-cell transfusions for patients with transfusion-dependent β-thalassemia. Long-term follow up for efficacy and safety is critical. Full study results are available at NEJM.org