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 pharm acological 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 esca lating doses from 40 U/kg to 300 U/kg three times a week subcutaneousl y during a period of 3 months. Maintenance therapy at the lowest effec tive dose was continued in responders. A dose response of CFu-E and BF U-E to Epo was analysed at the entry. Bone marrow examination with an in vitro study of hematopoietic progenitors was performed before and a fter the first three months. Seven of 20 patients responded: a total r ecovery 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 yea rs. No significant correlation was found between the in vitro and clin ical response. A non parametric analysis of responders and non respond ers emphasised the importance of a long delay between the diagnosis an d 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 stu dy offers evidence that patients with refractory anemias without exces s of blasts in the bone marrow respond to rhEpo at pharmacological dos es. Larger studies are required in order to define the patients who ma y respond and to elucidate the mechanism of the positive effect of rhE po.