Primary Outcome Measures:
- Outcome of bone marrow transplantation (BMT), e.g. survival and time to various complications will be analyzed with standard statistical methods [ Time Frame: 10 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To provide the potential for curative therapy of Kostmann's neutropenia, Shwachman's neutropenia, Diamond-Blackfan anemia by unrelated donor (URD) bone marrow or cord blood transplantation [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- To evaluate the rate of engraftment after transplantation of non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen consisting of busulfan, fludarabine, ATG and irradiation [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- To determine the incidence of acute and chronic graft-versus-host disease (GVHD), disease recurrence and three year survival in patients receiving transplantation with non-genotypic matched marrow or cord blood [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- To characterize the pharmacokinetic parameters in patients receiving 2 mg/kg/dose of intravenous (IV) busulfan twice daily [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Intervention Details:
Procedure: Stem cell transplant
This approach uses high doses of chemotherapy and irradiation in an attempt to kill the defective bone marrow, and allow it to be replaced by a healthy marrow from an unrelated individual
Drug: Busulfan, fludarabine and anti-thymocyte globulin (ATG)
drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation
Procedure: Total lymphoid irradiation
radiation therapy to specific areas of the body
Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.
Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).
Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.