Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia

著者: Alexis A. Thompson, Mark C. Walters, Janet L. Kwiatkowski, John E.J. Rasko, Jean‐Antoine Ribeil, Suradej Hongeng, Elisa Magrin, Gary J. Schiller, Emmanuel Payen, Michaëla Semeraro, Despina Moshous, François Lefrère, Hervé Puy, Philippe Bourget, Alessandra Magnani, Laure Caccavelli, Jean‐Sébastien Diana, Felipe Suarez, Fabrice Monpoux, Valentine Brousse, Catherine Poirot, Chantal Brouzes, Jean–François Méritet, Corinne Pondarré, Yves Beuzard, Stany Chrétien, Thibaud Lefèbvre, David T. Teachey, Usanarat Anurathapan, P. Joy Ho, Christof von Kalle, Morris Kletzel, Elliott Vichinsky, Sandeep Soni, Gábor Veres, Olivier Nègre, Robert W. Ross, David Davidson, Alexandria Petrusich, Laura Sandler, Mohammed Asmal, Olivier Hermine, Mariane De Montalembert, Salima Hacein‐Bey‐Abina, Stéphane Blanche, Philippe Leboulch, Marina Cavazzana - New England Journal of Medicine, NEJM 2018 被引用: 661

BACKGROUND: ) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia. METHODS: , transfusion requirements, and average vector copy number. RESULTS: genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed. CONCLUSIONS: Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe β-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials.gov numbers, NCT01745120 and NCT02151526 .).