Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

Abstract

BACKGROUND AND OBJECTIVE:

Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (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 rHuEpo +/- 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 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 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) subcutaneosly administered G-CSF (1 microg/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 of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive 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 CR 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 showed that of the different variables evaluated only the Scandinavian-American 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 cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded.

INTERPRETATION AND CONCLUSIONS:

Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

• Authors: A F Remacha, B Arrizabalaga, A Villegas, R Manteiga, T Calvo, A Julià, I Fernández Fuertes, F A González, L Font, J Juncà, A del Arco, J J Malcorra, E P Equiza, B P de Mendiguren, M Romero
• Journal: Haematologica (Haematologica) Vol. 84 Issue 12 Pg. 1058-64 (Dec 1999) ISSN: 0390-6078 [Print] Italy
• PMID: 10586205 (Publication Type: Clinical Trial, Clinical Trial, Phase IV, Controlled Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Recombinant Proteins
• Erythropoietin
• Granulocyte Colony-Stimulating Factor

Topics

• Adult
• Aged
• Aged, 80 and over
• Drug Therapy, Combination
• Erythropoietin (administration & dosage)
• Female
• Follow-Up Studies
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Patient Compliance
• Predictive Value of Tests
• Recombinant Proteins (therapeutic use)