I. Evaluate the toxicity of amifostine in patients with bone marrow failure related to
II. Determine the efficacy of this treatment regimen in this patient population.
III. Evaluate the effect of this treatment regimen on bone marrow progenitor cell
proliferation and peripheral blood mononuclear cell apoptosis in these patients.
This is a dose escalation study.
Patients receive amifostine IV over 3-5 minutes three times a week for three weeks.
Cohorts of 3 patients receive one of three dose levels of amifostine. The maximum tolerated
dose is defined as the dose preceding that at which 2 of 6 patients experience dose limiting
Patients are followed weekly for 3 weeks.
PROTOCOL ENTRY CRITERIA:
Diagnosis of Fanconi's anemia by conventional diepoxybutane or mitomycin sensitivity
assays, or molecular testing
Bone marrow failure verified on at least 3 occasions in the preceding 3 months by any one
of the following: hemoglobin less than 8 g/dL; absolute neutrophil count less than
1,000/mm3; platelet count less than 30,000/mm3; symptomatic bone marrow failure (e.g.,
exercise limitation from anemia or spontaneous bleeding from thrombocytopenia)
Evidence consistent with myelodysplastic syndrome allowed if less than 5% blasts on bone
marrow aspiration; clonality on bone marrow cytogenetic analysis OR morphological changes
on bone marrow aspirate
Refusal of or unsuccessful with prior conventional therapies
Biologic therapy: No prior bone marrow transplantation; no concurrent hematopoietic growth
Endocrine therapy: No concurrent androgens
Hepatic: Bilirubin no greater than 2 times normal AST no greater than 3 times normal ALT
no greater than 6 times normal
Renal: Creatinine no greater than 2 times normal
Other: No prior malignancy; no active bacterial, viral, or fungal infection requiring
therapy other than prophylaxis; not pregnant; negative pregnancy test