Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only viable cure for children who suffer from a wide variety of rare, serious non-malignant diseases, such as Fanconi Anemia, Hurler syndrome, and hemophagocytic lymphohistiocytosis. A major obstacle to the success of HSCT is morbidity and mortality from graft versus host disease (GVHD), driven by donor T cells recognizing and reacting against disparate host antigens. This trial is being conducted as a step toward testing the long-term hypothesis that the costimulation blockade agent abatacept can be added to a standard post-transplant GVHD prophylaxis regimen, cyclosporine and mycophenolate mofetil, to improve disease-free survival after unrelated hematopoietic stem cell transplantation (HSCT) using low dose total body irradiation based conditioning for children with non-malignant diseases. This study will have the following Specific Aims.
Specific Aim #1: To conduct a randomized, open-label multicenter pilot, assessing the tolerability of two dose numbers of abatacept (n=20). Patients will be randomly assigned to receive four doses (arm A;10 mg/kg IV on days -1, +5, +14 and +28), a schedule well tolerated by adolescents and adults with hematologic malignancies in a previous pilot, or six doses (arm B;10 mg/kg IV on days -1, +5, +14, +28, +56 and +84). Abatacept will be combined with cyclosporine and mycophenolate mofetil.
Specific Aim #2: to compare the immunological effects of four and six doses.