Study of High Dose Cyclophosphamide in Patients With Severe Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria

High Dose Cyclophosphamide for the Treatment of Severe Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria

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 hemoglobinuria.

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
    • 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