title: Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes.
abstract: OBJECTIVE
  Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopoietic progenitor cell disorders, and patients with MDS regularly develop anemia and frequently become transfusion-dependent. Treatment with erythropoietin (EPO) has been tried to correct anemia with only limited success with response rates ranging from 16% to 25%. However, it is becoming evident that the generally rather low response rate of EPO in patients with MDS will be improved by the combination of EPO with either G-CSF or GM-CSF.
  
  
  METHODS
  Here, we analyzed the results from the literature (six papers and one abstract using EPO plus G-CSF, and seven papers using EPO plus GM-CSF).
  
  
  RESULTS
  Among all trials the cytokine dose and schedule varied, and the response criteria were not uniform. The average response rate for improving anemia was 41% in 207 patients treated with EPO and G-CSF, and 26% in 154 patients treated with EPO and GM-CSF. There were higher response rates for refractory anemia (RA) (45%), ringed sideroblasts (RARS) (47%), and excess of blasts (RAEB) (38%) compared with blasts in transformation (RAEBT) (17%) for the treatment with EPO plus G-CSF. The corresponding response rates for treatment with EPO plus GM-CSF were 30% (RA), 29% (RARS), 16% (RAEB), and 0% (RAEBT), respectively. Prolonged administration even showed a higher increment in the response rates.
  
  
  CONCLUSIONS
  In conclusion, the combination of EPO with G-CSF is probably superior to EPO plus GM-CSF. There seems to be a positive correlation between the duration of cytokine treatment and response rates, and higher response rates in early MDS stages compared to advanced entities. However, controlled studies are mandatory to evaluate the role of the combined cytokine treatment in patients with MDS.
authors.affiliation: Department of Medicine II (Oncology-Hematology-Endocrinology), Friedrich-Schiller-University Jena, 07740 Jena, Germany. christoph.kasper@med.uni-jena.de
authors.forename: C
authors.initials: C
authors.lastname: Kasper
authors.forename: J
authors.initials: J
authors.lastname: Zahner
authors.forename: H G
authors.initials: HG
authors.lastname: Sayer
mesh_terms: D000740:Anemia / Q000188:drug therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D004921:Erythropoietin / Q000008:administration & dosage*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011994:Recombinant Proteins
chemical_list: D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor