Phase III Evaluation of EPO With or Without G-CSF Versus Supportive Therapy Alone in the Treatment of Myelodysplastic Syndromes

OBJECTIVES: Compare the benefit of erythropoietin 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. Evaluate whether adding filgrastim (G-CSF) or increasing the erythropoietin dose will reduce the transfusion requirement in patients who do not respond to erythropoietin alone. To compare the benefit of erythropoietin versus supportive care alone on quality of life (QOL) in persons with myelodysplastic syndromes. 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 erythropoietin treatment (yes vs no), and erythropoietin 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 erythropoietin alone. Arm II (Erythropoietin): Patients receive erythropoietin subcutaneously (SC) or intravenously (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 erythropoietin SC daily for up to 6 months. Patients with no response to G-CSF and lower-dose erythropoietin may proceed to a higher dose of erythropoietin. 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. ACTUAL ACCRUAL: A total of 118 patients were accrued for this study.