title: Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.
abstract: 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.
  
  
  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.
  
  
  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.affiliation: Hospital de Sant Pau, Hematology Department, Avda Padre Claret 167, Barcelona 08025, Spain. 2107@hsp.santpau.es
authors.forename: A F
authors.initials: AF
authors.lastname: Remacha
authors.forename: B
authors.initials: B
authors.lastname: Arrizabalaga
authors.forename: A
authors.initials: A
authors.lastname: Villegas
authors.forename: R
authors.initials: R
authors.lastname: Manteiga
authors.forename: T
authors.initials: T
authors.lastname: Calvo
authors.forename: A
authors.initials: A
authors.lastname: Julià
authors.forename: I
authors.initials: I
authors.lastname: Fernández Fuertes
authors.forename: F A
authors.initials: FA
authors.lastname: González
authors.forename: L
authors.initials: L
authors.lastname: Font
authors.forename: J
authors.initials: J
authors.lastname: Juncà
authors.forename: A
authors.initials: A
authors.lastname: del Arco
authors.forename: J J
authors.initials: JJ
authors.lastname: Malcorra
authors.forename: E P
authors.initials: EP
authors.lastname: Equiza
authors.forename: B P
authors.initials: BP
authors.lastname: de Mendiguren
authors.forename: M
authors.initials: M
authors.lastname: Romero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D010349:Patient Compliance; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor