A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes

To evaluate the effect of recombinant human erythropoietin (rHuEpo) on the haemoglobin level and transfusion requirement in low-risk myelodysplastic s yndromes (MDS), 87 patients were enrolled in a randomized double-blind plac ebo-controlled study. 44 patients were assigned to epoetin alpha (150 U/kg/ d s.c for 8 weeks) and 43 to placebo arms. MDS types were homogenous in bot h groups: refractory anaemia (RA) 47.7-48.8%, refractory anaemia with ringe d sideroblasts (RAS) 20.5-25.6%, refractory anaemia with excess of blasts ( RAEB) (blasts < 10%) 31.8-25.6%. 14/38 evaluable patients responded to epoetin alpha versus 4/37 to placebo (P=0.007). 50% of RA responded to epoetin alpha versus 5.9% to placebo (P = 0.0072), RAS 37.5% v 18.2% (P = 0.6) and RAEB 16.7% v 11.1% (P = 1.00). 60 % of non-pretransfused patients responded to epoetin alpha (Hb 8.35 +/- 0.7 3 to 10.07 +/- 1.87 g/dl), whereas a slight decrease was observed in the pl acebo group (8.4 +/- 0.66 to 8.19 +/- 0.92 g/dl) (P = 0.0004). Percentage o f transfused patients was similar in both arms. Basal erythropoietin (Epo) serum levels >200 mU/l predicted for a non-response. At week 4 sTfR levels were increased > 50% in responders (P = 0.013), whereas an increase < 18% p redicted for non-response (P = 0.006). Leucocyte and platelet counts were n ot influenced by epoetin alpha treatment. Adverse events occurred in 31.8% of the rHuEpo-treated versus 42.9% of the placebo-treated patients (P = 0.2 ), and seven patients did not complete the course. In conclusion, rHuEpo wa s effective in the treatment of low-risk MDS, RA subtype, no transfusions p rior to rHuEpo therapy, and low basal Epo levels were associated with highe r probability of response. Soluble transferrin receptor level at the fourth week was an early predictor of response.