Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant in Treating Patients With Sickle Cell Anemia and Other Blood Disorders

• Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT) [ Time Frame: 1 year after bone marrow transplant ] [ Designated as safety issue: No ]
  
• Risk-stratified estimates of 2-year progression-free survival [ Time Frame: 2 years from bone marrow transplant ] [ Designated as safety issue: No ]
  

• Time to recovery of circulating neutrophils and platelets after chemotherapy [ Time Frame: 60 days from bone marrow transplant ] [ Designated as safety issue: No ]
  
• Donor chimerism at 30, 60, 180, and 365 days after bone marrow transplant [ Time Frame: 1 year from bone marrow transplant ] [ Designated as safety issue: No ]
  
• Development of graft-vs-host disease [ Time Frame: 1 year from bone marrow transplant ] [ Designated as safety issue: No ]
  

Biological: G-CSF
Donors will receive subcutaneous injections in the stomach (or other fatty area of the body) of G-CSF at 10 μg/kg/day for 5 consecutive days until the day of the harvest, the day we collect bone marrow for the transplant.
Other Name: Filgrastim®
Drug: cyclophosphamide
Cyclophosphamide (CTX) 14.5 mg/kg intravenously for 2 days before and after transplant.
Drug: fludarabine phosphate
Fludarabine 30 mg/M2 intravenously for 5 days before bone marrow transplant
Drug: mycophenolate mofetil
Mycophenolate mofetil 15 mg/kg by mouth three times a day daily for 30 days beginning 5 days after bone marrow transplant.
Drug: Sirolimus
The first dose of Sirolimus is 6 mg and is taken by mouth 5 days after bone marrow transplant. On the 6th day after bone marrow transplant, the dose of Sirolimus is 2 mg by mouth daily for 1 year.
Procedure: Allogeneic bone marrow transplantation
An allogeneic bone marrow transplant is a procedure that involves taking bone marrow from a donor and giving it to a recipient.
Radiation: total-body irradiation
Radiation of the total body will be administered the day before bone marrow transplant.
Drug: Levetiracetam
Levetiracetam 500 mg orally twice a day 6 days before transplant and for 1 year after transplant. Levetiracetam prevents seizures.
Other Name: Keppra

OBJECTIVES:

• Determine the transplant-related mortality and progression-free survival of patients with severe hemoglobinopathies receiving nonmyeloablative conditioning comprising fludarabine phosphate, cyclophosphamide, and total-body irradiation followed by partially HLA-mismatched bone marrow transplantation from first-degree relatives or HLA-matched donors.
• Characterize donor hematopoietic chimerism at 30, 60, and 180 days after transplantation in these patients.
• Determine the hematologic and non-hematologic toxicity of this regimen in these patients.

OUTLINE:

• Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients also undergo total-body irradiation on day -1.
• Bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Donors receive filgrastim (G-CSF) subcutaneously beginning on day -5 to day -1.
• Graft-versus-host disease prophylaxis: Patients receive sirolimus orally daily on days 5-365 and oral mycophenolate mofetil 3 times a day on days 5-35.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.