Allogeneic Hematopoietic Cell Transplantation for Chronic Granulomatous Disease: Controversies and State of the Art

Abstract

Chronic granulomatous disease (CGD) is a congenital disorder characterized by recurrent life-threatening bacterial and fungal infections and development of severe inflammation secondary to a congenital defect in 1 of the 5 phagocyte oxidase (phox) subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Hematopoietic cell transplant (HCT) is a curative treatment for patients with CGD that provides donor neutrophils with functional NADPH and superoxide anion production. Many characteristics of CGD, including preexisting infection and inflammation and the potential for cure with mixed-donor chimerism, influence the transplant approach and patient outcome. Because of the dangers of short-term death, graft-versus-host disease, and late effects from chemotherapy, HCT historically has been reserved for patients with high-risk disease and a matched donor. However, as advances in CGD and HCT treatments have evolved, recommendations on transplant eligibility also must be amended, but the development of modern guidelines has proven difficult. In this review, we provide an overview of HCT in patients with CGD, including the debate over HCT indications in them, the unique aspects of CGD that can complicate HCT, and a summary of transplant outcomes.