SEQUENTIAL ADMINISTRATION OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGECOLONY-STIMULATING FACTOR AND HUMAN ERYTHROPOIETIN FOR TREATMENT OF MYELODYSPLASTIC SYNDROMES

Treatment of myelodysplastic syndromes (MDS) with recombinant human er ythropoietin (Epo) is successful in only 10% to 25% of patients. We pe rformed a pilot study in 10 anaemic patients with MDS to examine wheth er sequentially applied recombinant human granulocyte-macrophage colon y-stimulating factor (GM-CSF) and Epo improves haemoglobin levels and/ or reduces red blood cell transfusion requirements. Morphological diag noses of patients were refractory anaemia (RA) in 3 cases, RA with rin g sideroblasts in 3 cases and RA with excess blasts in 4 cases. GM-CSF was given subcutaneously at a dose of 150 mu g/m(2)/d during the init ial 10 days. From day 11, Epo was administered by subcutaneous injecti ons for 8 weeks at a dose of 100 U/kg/d and subsequently at an escalat ed dose of 200 U/kg/d in 3 patients. Changes in reticulocyte counts, h aemoglobin levels, RBC support and ferrokinetic parameters were compar ed with pretreatment values. Two out of 8 evaluable patients showed a rise in haemoglobin levels at week 8 and 10, respectively, and lost th eir transfusion dependency for a period of 13 and 27 weeks. In 1 patie nt, haemoglobin level increased only after dose escalation of Epo (200 U/kg/d). Leukocyte counts remained uneffected by treatment with Epo, while 1 patient showed a 4-fold increase in platelet numbers. Toxicity was mild. Two patients died of pneumonia and global heart failure, re spectively, unrelated to growth factor therapy. Based on this pilot st udy, we conclude that sequential treatment with GM-CSF and Epo does no t increase erythroid responses in anaemic patients with MDS. Because o f the delayed increase in haemoglobin in both responders, we surmise t hat the beneficial effects were induced by Epo alone.