ORIGINAL PAPER C. Kasper Æ J. Zahner Æ H.G. Sayer Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes Received: 12 April 2002 /Accepted: 5 July 2002 / Published online: 27 August 2002 Ó Springer-Verlag 2002 Abstract Purpose: 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. Method: 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 re- fractory 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. Conclusion: In conclusion, the combi- nation 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. Keywords Erythropoietin Æ Anemia Æ Myelodysplastic syndrome (MDS) Æ Granulocyte- colony-stimulating factor (G-CSF) Æ Granulocyte-macrophage colony-stimulating factor (GM-CSF) Introduction Myelodysplastic syndromes (MDS) comprise a hetero- geneous group of hemopoietic progenitor cell disorders characterized by cytopenia and dysplasia. Patients regularly develop moderate to severe anemia, thromb- ocytopenia, and neutropenia, frequently become trans- fusion-dependent, and acquire infections. In 1982 the French-American-British (FAB) group proposed a classification, defining five subgroups on morphological criteria (Bennett et al. 1982): refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), re- fractory anemia with excess of blasts (RAEB), chronic myelomonocytic leukemia (CMML), and refractory anemiawithexcessofblastsintransformation(RAEBT). Recently, a new WHO classification was introduced (Harris et al. 1999) which is still a matter of debate (No¨sslinger et al. 2001). The International Prognostic Scoring System (IPSS) defines prognostic groups on the basis of the karyotype, number of cytopenias, and blast count (Greenberg et al. 1997) and may be useful for risk stratification and therapeutic decision. Allogeneic stem cell transplantation is the only curative treatment approach but is restricted to younger patients with a histocompatible donor. Thus, best supportive care remains the basic treatment for most of the patients with low- to intermediate MDS variants including red blood cell (RBC) transfusions and application of anti- biotics. J Cancer Res Clin Oncol (2002) 128: 497–502 DOI 10.1007/s00432-002-0372-z C. Kasper (&) Æ H.G. Sayer Department of Medicine II (Oncology-Hematology-Endocrinology), Friedrich-Schiller-University Jena, 07740 Jena, Germany E-mail: christoph.kasper@med.uni-jena.de J. Zahner Medical Department, Chugai Pharma, Frankfurt am Main, Germany