Bone Marrow Transplantation in Treating Children With Sickle Cell Disease
Bone Marrow Transplantation in Treating Children With Sickle Cell Disease
RATIONALE: Sickle cell disease is an inherited disorder in which abnormal, crescent-shaped
 red blood cells interfere with the ability of the blood to carry oxygen through the body and
 can cause severe pain, stroke, and organ damage. Bone marrow transplantation, is a procedure
 in which the soft, sponge-like tissue in the center of bones producing white blood cells, red
 blood cells, and platelets is replaced by bone marrow from a another person. Bone marrow
 transplantation may be an effective treatment in relieving the symptoms of sickle cell
 disease.

 PURPOSE: Phase I/II trial to study the effectiveness of bone marrow transplantation in
 treating children who have sickle cell disease.
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