Gene therapy may help patients with transfusion-dependent β-thalassemia reduce or eliminate the need for blood transfusions, according to a study published in the New England Journal of Medicine.

Alexis A. Thompson, MD, MPH, from the Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine, and associates conducted 2 multicenter, nonrandomized, open-label, single-dose phase 1-2 studies to determine the security and efficiency of gene therapy in patients with severe, transfusion-dependent β-thalassemia.

Twenty-two patients between ages 12 and 35 years with β-thalassemia were enrolled in 1 of 2 studies: 18 participants in the HGB-204 study and 4 participants in the HGB-205 study. Of the cohort, 13 were enrolled in long-term follow-up. The HGB-204 study was international with a patient follow-up between 15 and 38 months, while the HGB-205 study involved treatment of 3 patients with sickle cell disease and 4 with β-thalassemia with a patient follow-up from 20 months to more than 3 years.

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Both studies included the infusion of autologous hematopoietic stem cells via LentiGlobin viral vector BB305 transduction ex vivo with a functional HBB gene. Followed by patient myeloablative busulfan conditioning, patients were infused with the treated stem cells.

Of the 13 patients with reduced β-globin synthesis (non–β0/ β0), 12 patients reached normal HbA-levels and did not require RBC transfusions during the median follow-up of 26 months. Nine patients with no β-globin synthesis (β0/ β0) experienced a reduction in frequency (median 74%) and volume (median 73%) of transfusions, and 3 of the 9 patients did not require any transfusions during follow-up.

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“In conclusion, we found that gene therapy with LentiGlobin drug product succeeded in overcoming a principal limitation of allogeneic hematopoietic-cell transplantation, which is a lack of a histocompatible donor,” wrote the authors. “Although several patients with a β00 genotype or equivalent disease have stopped receiving red-cell transfusions, and ongoing improvements in manufacturing of the drug product hold promise for achieving similar results in most patients with a β00 genotype, even the partial reduction in transfusion requirements that we observed in these patients may result in a reduction in iron loading (and thereby long-term damage to target organs) and in increased life expectancy.”


Thompson AA, Walters MC, Kwiatkowski J, et al. Gene therapy in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2018; 378:1479-1493