Efficacy of recombinant human erythropoietin in the treatment of refractory anemias without excess of blasts in myelodysplastic syndromes.

To determine the efficacy of recombinant human erythropoietin at pharmacological doses in myelodysplastic syndromes (MDS) without excess of blasts, 20 patients with refractory anemias (RA) or refractory anemias with ring sideroblasts (RARS) were treated in an open study with escalating doses from 40 U/kg to 300 U/kg three times a week subcutaneously during a period of 3 months. Maintenance therapy at the lowest effective dose was continued in responders. A dose response of CFu-E and BFU-E to Epo was analysed at the entry. Bone marrow examination with an in vitro study of hematopoietic progenitors was performed before and after the first three months. Seven of 20 patients responded: a total recovery was observed in 3 patients; one became transfusion independent and a reduction of 50% of the transfusion requirement was achieved in 3 others. 3 patients are still receiving treatment for 2, 3 and 4 years. No significant correlation was found between the in vitro and clinical response. A non parametric analysis of responders and non responders emphasised the importance of a long delay between the diagnosis and the treatment, (p = 0.024) and an endogenous Epo level less than 100 mU/ml (p = 0.025) in order to predict the efficacy of rhEpo. This study offers evidence that patients with refractory anemias without excess of blasts in the bone marrow respond to rhEpo at pharmacological doses. Larger studies are required in order to define the patients who may respond and to elucidate the mechanism of the positive effect of rhEpo.