Donor Stem Cell Transplant After Busulfan, Fludarabine, Methylprednisolone, and Antithymocyte Globulin in Treating Patients With Bone Marrow Failure Syndrome

OBJECTIVES:

• To evaluate the efficacy of HLA-haploidentical familial donor hematopoietic stem cell transplantation after reduced-intensity conditioning regimen comprising busulfan, fludarabine phosphate, and anti-thymocyte globulin in patients with bone marrow failure syndromes.

OUTLINE:

• Reduced-intensity conditioning regimen: Patients receive busulfan IV daily on days -7 and -6, fludarabine phosphate IV over 30 minutes on days -7 to -2, anti-thymocyte globulin (ATG) IV over 4 hours on days -4 to -1, and methylprednisolone IV over 30 minutes starting 30 minutes before ATG on days -4 to -1.
• HLA-haploidentical donor hematopoietic stem cell transplantation: Patients receive donor hematopoietic stem cells via Hickman catheter over 1 hour on days 0 or 1.
• Graft-versus-host-disease prophylaxis (GVHD): Patients receive cyclosporine IV over 2-4 hours every 12 hours starting on day -1 (cyclosporine can be given orally once oral medication can be tolerated) and methotrexate IV on days 2, 4 , 7, and 12. In the absence of GVHD, cyclosporine is tapered starting between days 30 to 60.

After completion of study treatment, patients are followed periodically for 1 year.

DISEASE CHARACTERISTICS:

• Diagnosis of any of the following bone marrow failure syndromes:

• Severe aplastic anemia, meeting 1 of the following criteria:

• Not responsive to immunosuppressive therapy
• With recurrent cytopenia after immunosuppressive therapy or allogeneic hematopoietic cell transplantation
• Low-risk myelodysplastic syndrome, including any of the following:

• Refractory anemia
• Refractory anemia with ringed sideroblasts
• Refractory cytopenia with multi-lineage dysplasia
• Paroxysmal nocturnal hemoglobinuria, meeting 1 of the following criteria:

• With thrombotic episodes
• With severe cytopenia
• No willing, suitable HLA-compatible donor in family or in donor registries

• Related donor with HLA-haploidentical mismatch at three or less of 6 loci
• Patients with very severe neutropenia (< 200/μL) or febrile episodes, who feel urgent need for allogeneic hematopoietic cell transplantation, are eligible without a search for HLA-matched unrelated donors

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Bilirubin < 2.0 mg/dL
• AST < 3 times upper limit of normal
• Creatinine < 2.0 mg/dL
• Ejection fraction > 40% by MUGA scan

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics