OBJECTIVES: I. Confirm the efficacy demonstrated in a pilot study using high dose
cyclophosphamide in patients with severe aplastic anemia.
II. Determine whether the addition of filgrastim (G-CSF) to high dose cyclophosphamide
shortens the time to recovery in these patients.
III. Determine whether this regimen is efficacious in treating paroxysmal nocturnal
PROTOCOL OUTLINE: Patients receive high dose cyclophosphamide IV on days 1-4. Beginning on
day 10, patients receive filgrastim (G-CSF) until the absolute neutrophil count is greater
than 1,000/mm3 for 2 consecutive days.
Patients are followed every 3 months for at least 2 years and annually thereafter.
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics-- Acquired severe aplastic anemia or paroxysmal nocturnal
hemoglobinuria Not a candidate for allogeneic bone marrow transplantation Must meet one of
the following criteria: - Severe aplastic anemia Less than 25% bone marrow cellularity and
depression in two of three blood counts (reticulocytes less than 40,000/mm3, platelet
count less than 20,000/mm3 and granulocytes less than 500/mm3) - Life-threatening
paroxysmal nocturnal hemoglobinuria Absolute neutrophil count less than 500/mm3, platelet
transfusion dependent, or thrombotic disease No Fanconi anemia No abnormal cytogenetics
--Patient Characteristics-- Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular:
Cardiac ejection fraction at least 45% Other: Not preterminal or moribund Not pregnant