Effect of recombinant human erythropoietin combined with granulocyte/macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome

This randomized, placebo-controlled trial was designed to assess the effica cy and safety of therapy with granulocyte-macrophage colony-stimulating fac tor (GMCSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patien ts with myelodysplastic syndrome. Sixty-six patients were enrolled accordin g to the following French-American-British classification: refractory anemi a (20), refractory anemia with excess blasts (35), refractory anemia with r inged sideroblasts (9), and refractory anemia with excess blasts in transfo rmation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) a nd randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 mu g/kg.d) + epoet in alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 mu g/kg.d) + placebo (3 t imes/wk), The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa, Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patien ts in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients w ith GM-CSF + placebo group (P = NS), Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS), S imilarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 an d 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- e poetin alfa had no effect on mean platelet count. Treatment was well tolera ted in most patients, though 10 withdrew from the study for reasons related predominantly to GMCSF toxicity.