Clinical Use of Recombinant Human Erythropoietin in the Treatment of Myelodysplastic Syndromes

Abstract

Supportive care with blood products is still the mainstay of therapy for anemia occurring in patients with myelodysplastic syndromes (MDS). Recently, recombinant DNA technology has enabled us to develop erythropoietin as a therapeutic agent, and a few published studies have already assessed the clinical effects of the administration of recombinant human erythropoietin (r-HuEPO) to patients with MDS. In a first pilot study, two patients with refractory anemia (RA) were treated with r-HuEPO, administered i.v. with an initial dose of 50 U/kg body weight (bw) three times per week up to a maximum dose of 500 U/kg bw three times per week. In one case a good clinical response was achieved by the administration of r-HuEPO at the maximum dose. In another study, r-HuEPO at the doses of 3,000 to 12,000 U three times a week was administered i.v. for at least four weeks to 8 patients with MDS, observing some good clinical responses in three of them. The same authors confirmed response to r-HuEPO in 8 out of 33 patients in a larger multicenter study. More recently, 5 clinical responses to r-HuEPO were reported among 12 patients with MDS treated with escalating doses of 600 up to 3,000 U/kg bw per week. These results have not been confirmed by another phase I1 study, in which in 12 patients with MDS and anemia, r-HuEPO was given subcutaneously three times a week at doses ranging between 50 to 250 U/kg bw without any clinical effect. Finally in a recent randomized, placebo-controlled, double-blind trial, 20 patients with RA and RARS were treated with pharmacologic doses of r-HuEPO ranging between 1,200 to 1,600U/kg i.v. twice weekly, with overall responses occurring in 4 of 17 (24%) of evaluable patients. In all the above studies, r-HuEPO was well tolerated and no serious side effects were seen, even when very high doses of r-HuEPO were used. When the responders were compared to nonresponders, no clear difference was found between the two groups with respect to age, gender, diagnosis and time since diagnosis or previous treatment. Interestingly enough, response to r-HuEPO has not been significantly related to baseline serum erythropoietin concentration, indicating that the preliminary assessment of this parameter does not predict the clinical response to r-HuEPO. In conclusion, available data indicate that r-HuEPO administration is an effective treatment for a certain number of MDS patients; its clinical use, even at very high doses, has been shown to be safe and without any relevant side-effect. However, the criteria for response to r-HuEPO therapy, as well as the indication for therapy, remain to be clarified.