Erythropoietin plus granulocyte colony-stimulating factor in the treatmentof myelodysplastic syndromes. Identification of a subgroup of responders

Background and Objectives. Anemia leading to transfusion is probably the mo st important problem in patients with myelodysplastic syndromes (MDS). Huma n recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating fa ctor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuE po +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. Design and Methods. A non-randomized multicenter trial was carried out in 3 2 patients with MDS. The Inclusion criteria were age greater than or equal to 18 years, refractory anemia (RA) or refractory anemia with ringed sidero blasts, Hb less than or equal to 100 g/L or receiving transfusions and seru m erythropoietin less than or equal to 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneously administe red G-CSF (1 mu g/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose o f growth factors was tapered down. Several variables, including the score p ublished by the Scandinavian-American group, were used as possible predicti ve variables. Results. An erythroid response was observed in 16 patients (50%); in 12 it was a CR and In 4 it was a PR. During the period of rHuEpo administration, 7 OR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis sho wed that of the different variables evaluated only the Scandinavian-America n response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of ca ses responded). In contrast, when this score was less than or equal to 1 on ly 15% of the cases responded. Interpretation and Conclusions. Use of the Scandinavian-American response s core is to be recommended in a patient-oriented approach to treating MDS ca ses with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its ma in drawback being its cost. However, a long-term study evaluating the regim en's cost-benefit ratio is warranted. (C) 1999, Ferrata Storti Foundation.