Treatment of Chronic Granulomatous Disease With Allogeneic Stem Cell Transplantation Versus Standard of Care

Chronic Granulomatous Disease (CGD) is one of several inherited disorders of leukocyte function. Patients are profoundly immunocompromised and plagued early in life with recurrent and often life threatening infections. Allogeneic stem cell transplantation significantly improves immune function in patients with CGD. The primary objective of this study is to investigate efficacy of a novel approach to allogeneic stem cell transplantation, which is designed to promote partial or complete donor stem cell engraftment (hematopoietic chimerism) with reduced transplant related morbidity and mortality. In an attempt to reduce toxicity from pre-transplant bone marrow conditioning, a highly immunosuppressive, low intensity bone marrow conditioning regimen will be used. Patients will be transplanted with peripheral blood stem cells from an HLA identical family member. The graft will be enriched for hematopoietic stem cells in an attempt to decrease the risk of graft versus host disease. Donor T-cells will be infused at various time points following the transplant to augment donor hematopoietic chimerism and aid in immune reconstitution. Patients treated with this approach will be compared to patients who are considered transplant-eligible but lack an HLA identical family member. These patients will be treated using the current standard of care. The primary end points of this study are to demonstrate reduced incidence of CGD-like infections in the transplanted patients compared to the controls (efficacy) with acceptable incidence of acute and chronic graft versus host disease and transplant related mortality (safety). Long term follow up data from transplanted patients and concurrent controls will be analyzed to confirm the association between establishment of hematopoietic chimerism and clinical benefit.