Phase I/II Study of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Cell Transplantation in Patients With Fanconi's Anemia

PROTOCOL OUTLINE: Donor bone marrow, peripheral blood, or umbilical cord blood is processed to harvest CD34+ cells.

Patients receive preparative cytoreductive therapy comprising total body irradiation on day -6; cyclophosphamide IV over 2 hours on days -5 to -2; fludarabine IV over 30 minutes on days -5 to -2; methylprednisone IV on days -5 to 24; anti-thymocyte globulin IV over 4-6 hours on days -5 to -1; cyclosporine IV over 2 hours every 12 hours (every 8 hours for patients less than 40 kg in weight) on days -3 to 180, and then tapering in the absence of graft-versus-host disease; hematopoietic cell transplantation on day 0; and filgrastim (G-CSF) IV starting on day 1 and continuing until blood counts recover.

Patients are followed at days 60, 90, and 180, and then annually for 3 years.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Patients with a diagnosis of Fanconi's anemia AND Aplastic anemia OR Myelodysplastic syndrome OR Acute leukemia with or without chromosomal anomalies Aplastic anemia as defined by having at least one of the following: Platelet count less than 20,000/mm3 Absolute neutrophil count less than 500/mm3 Hemoglobin less than 8 g/dL
• Myelodysplastic syndrome with multilineage dysplasia With or without chromosomal anomalies
• Hematologic malignancy (e.g., acute myeloid leukemia, acute lymphoblastic leukemia, or B-cell non-Hodgkin's lymphoma)
• No greater than 30% blasts in bone marrow or greater than 5% blasts in peripheral blood
• No active CNS leukemia at time of transplantation
• Must have an HLA A, B, DRB1 identical or 1 antigen mismatched related (nonsibling) or unrelated bone marrow, peripheral blood, or umbilical cord blood donor

--Prior/Concurrent Therapy--

• Radiotherapy: No prior radiotherapy that would preclude total body irradiation
• Surgery: Not specified

--Patient Characteristics--

• Performance status: Karnofsky 70-100% OR Lansky 50-100%
• Hematopoietic: See Disease Characteristics
• Hepatic: No hepatic failure (e.g., coagulopathy or ascites)
• Renal: Creatinine clearance at least 40 mL/min
• Cardiovascular: Ejection fraction at least 45%
• Other: No active uncontrolled infection within one week of transplantation No malignant solid tumor (e.g., squamous cell carcinoma of the head, neck, or cervix) within 2 years of transplantation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception