• To assess the safety of the conditioning regimen using Cytoxan, total body irradiation (TBI) and Campath 1H in patients with severe aplastic anemia (SAA) [ Time Frame: 100 days, 1 year and 2 years post transplant ] [ Designated as safety issue: Yes ]
  

• To assess engraftment and the risk of graft failure in this patient population [ Time Frame: 28 and 100 days post transplant ] [ Designated as safety issue: Yes ]
  
• To assess the risk of GVHD, both acute and chronic [ Time Frame: 100 days, 1 year and 2 years post transplant ] [ Designated as safety issue: Yes ]
  
• To estimate survival at 100 days, 1 year and 2 years [ Time Frame: 100 days, 1 year, 2 years post transplant ] [ Designated as safety issue: No ]
  

Severe aplastic anemia (SAA) is a rare but serious disorder in children. Bone marrow transplant (BMT) with an HLA identical sibling is currently the treatment of choice for a child with SAA, as it offers a cure by restoration of normal hematopoiesis. The excellent results of marrow transplantation in children with HLA identical siblings and the low mortality and morbidity make transplantation the treatment of choice in young patients.

Rejection is likely to be caused by allosensitization of the recipient to minor histocompatibility antigens through the transfusion of red cells and platelets. As a result, it is recommended that transfusions be avoided as much as possible in patients with aplastic anemia who are being considered for BMT, and always those from the transplant donor. The addition of antithymocyte globulin (ATG) to the cyclophosphamide preparative regimen has also contributed to the lower risk of graft failure.

The other complication besides graft rejection, which is a major cause of late mortality and morbidity both as an immediate, and a delayed consequence of allogeneic BMT is Graft versus host disease (GVHD). GVHD is mediated by donor lymphocytes and histoincompatibility is a major risk factor for GVHD. There is also a clear association between age and risk of GVHD independent of the degree of histoincompatibility. The increased risks of GVHD with age contribute to poor survival post transplant in older patients. Thus excellent survival and low morbidity make allogeneic transplant the treatment of choice for children and adolescents.

Children with SAA who lack an HLA identical sibling donor need alternative therapy. Transplant from an unrelated donor is a potentially curative alternative in patients who fail immunosuppressive therapy. An unrelated marrow search is initiated usually at the time of starting the immunosuppressive therapy to save time if transplant becomes necessary.

Antithymocyte globulin (ATG) has been used with conventional conditioning to enhance depletion of the host's immune system with the intent of accelerating engraftment and reducing the risk of rejection.

Similarly, CAMPATH-I is a rat antibody that recognizes the CD52 cell surface marker. CAMPATH-1H is a humanized antilymphocyte monoclonal antibody. The Campath-1 antigen in humans (CD52) is predominantly expressed on peripheral blood lymphocytes, monocytes, and macrophages. CAMPATH-1H causes lysis of lymphocytes by fixing to CD52, a highly expressed, non-modulating antigen on the surface of lymphocytes. It mediates the lysis of lymphocytes via complement and antibody dependent cell mediated cytotoxicity mechanisms. Extensive clinical data on the use of CAMPATH in stem cell transplant is available. To date, antibodies of the Campath series have been used in over 2000 bone marrow transplants primarily for the prevention of GVHD but also for reduction of graft rejection.