PROTOCOL OUTLINE: This is a multicenter study. Patients undergo total body irradiation on day 0, followed by allogeneic bone marrow transfusion. Patients also receive fludarabine IV daily and cyclosporine IV twice a day on days -1 to 1. Patients then receive oral cyclosporine on days 1-90, and oral mycophenolate mofetil twice a day on days 0-27.

Patients are followed for 100 days, monthly for 6 months and then annually for 2 years.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of sickle cell anemia with clinically severe disease manifestations defined by: Recurrent painful events (at least 2 painful events in past year) which cannot be explained by other causes Pain lasts at least 4 hours Requires treatment with parenteral narcotics, equianalgesic dose of oral narcotics, or parenteral nonsteroidal antiinflammatory drugs Acute chest syndrome (ACS) with at least 2 episodes within past 2 years that required hospitalization, oxygen, and RBC transfusion Any combination of painful events and ACS episodes that total 2 events within the past year Abnormal cerebral MRI, abnormal angiography (MR or conventional), and abnormal neuropsychologic testing performance

No stage III or IV sickle cell lung disease

Genotypically HLA identical sibling donor available

--Prior/Concurrent Therapy--

No prior transfusions with greater than 5 units RBC

--Patient Characteristics--

Performance status: Karnofsky 70-100%

Hepatic:

• No active hepatitis
• No moderate/severe portal fibrosis

Renal: Glomerular filtration rate at least 30% predicted for age

Neurologic:

• No severe residual functional neurologic impairment
• Hemiplegia alone allowed

Other:

• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception