An Emerging Era of Clinical Benefit From Gene Therapy

The report in this issue of JAMA by Hacein-Bey Abina and colleagues¹ provides strong evidence that gene therapy using myeloid/lymphoid conditioning combined with subsequent infusion of lentivector-transduced autologous CD34⁺ hematopoietic stem cells (HSCs) achieves substantial restoration of immune function associated with prolonged clinical benefit to patients with severe phenotype Wiskott-Aldrich syndrome (WAS). Prior to treatment, 6 of the 7 patients included in the study had the highest WAS severity disease score of 5; all patients had experienced serious clinical events and complications that are the hallmark of classic WAS, including recurrent viral or bacterial infections, bleeding due to microthrombocytopenia, severe eczema, vasculitis, enteropathy, and other autoimmune problems.