OBJECTIVES:

• Compare the benefit of epoetin alfa vs standard transfusion support in reducing transfusion requirements in patients with myelodysplastic syndromes.
• Compare the clinical response, disease progression, and survival in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Determine the effect of pretreatment epoetin alfa levels on the response to epoetin alfa in these patients.
• Evaluate whether adding filgrastim (G-CSF) or increasing the epoetin alfa dose will reduce the transfusion requirement in patients who do not respond to epoetin alfa alone.
• Assess quality of life (QOL) of these patients and determine whether either cross-sectional or longitudinal differences in patients' QOL and fatigue are correlated with the use of the growth factors.

OUTLINE: This is a randomized, controlled, multicenter, cross-over study. Patients are stratified according to morphologic subtype (refractory anemia [RA] vs RA with ringed sideroblasts vs RA with excess blasts), transfusion requirement (yes vs no), prior epoetin alfa treatment (yes vs no), and epoetin alfa level (at least 200 mU/mL vs less than 200 mU/mL). Patients are randomized to one of two treatment arms.

• Arm I (standard transfusion support): Patients receive red cell and platelet transfusions for symptoms or to maintain hematocrit level of 25% or above. Patients undergo bone marrow aspirate and biopsy at 4 months and then every year until development of acute leukemia or completion of study. Patients with progressive disease may cross over to arm II after at least 4 months on study and up to 1 year from the time of randomization. Patients who cross over receive epoetin alfa alone.
• Arm II (epoetin alfa support): Patients receive epoetin alfa subcutaneously (SC) or IV daily. Patients undergo bone marrow aspirate and biopsy as in arm I. Treatment continues daily for a maximum of 1 year.

Patients with stable or progressive disease at day 120 receive filgrastim (G-CSF) SC daily or 3 days a week and epoetin alfa SC daily for up to 6 months. Patients with no response to G-CSF and lower-dose epoetin alfa may proceed to a higher dose of epoetin alfa.

Quality of life is assessed at baseline, every 4 months during study, and at study completion.

Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 139 patients will be accrued for this study within 3.6 years.

DISEASE CHARACTERISTICS:

• Histologically proven myelodysplastic syndromes

  • Refractory anemia (RA)
  • RA with ringed sideroblasts
  • RA with excess blasts (RAEB)
• RAEB patients must have a bone marrow blast count of less than 20% and less than 5% blast forms on peripheral blood
• No RAEB in transformation

• No chronic myelomonocytic leukemia

  • Secondary myelodysplastic syndromes allowed
• No splenomegaly greater than 6 cm below the left costal margin or greater than 3 times normal size

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-3

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Platelet count greater than 30,000/mm^3 (without platelet transfusions)
• Hematocrit less than 30% (pretransfusion)

Hepatic:

• Bilirubin less than 3 mg/dL

Renal:

• BUN less than 40 mg/dL OR
• Creatinine less than 2.0 mg/dL

Cardiovascular:

• No uncontrolled hypertension

Other:

• No sensitivity to E. coli-derived proteins
• No sensitivity to epoetin alfa or any of its components (e.g., human albumin)

• No documented iron deficiency

  • If marrow iron stain is not available, the transferrin saturation must be greater than 20% or ferritin greater than 100 ng/dL
• No active infection or bleeding
• No other uncontrolled malignancy
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior epoetin alfa allowed provided dosage was less than 30,000 units per week for less than 1 month duration
• At least 1 month since prior epoetin alfa
• At least 2 months since prior recombinant growth factor

Chemotherapy:

• At least 2 months since prior chemotherapy for other malignancy or autoimmune disease

Endocrine therapy:

• At least 2 weeks since prior androgens or steroids for treatment of myelodysplastic syndromes

Radiotherapy:

• Not specified

Surgery:

• Not specified