Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. 2002

C Kasper, and J Zahner, and H G Sayer
Department of Medicine II (Oncology-Hematology-Endocrinology), Friedrich-Schiller-University Jena, 07740 Jena, Germany. christoph.kasper@med.uni-jena.de

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.

UI MeSH Term Description Entries
D007377 Interleukin-3 A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Burst-Promoting Factor, Erythrocyte,Colony-Stimulating Factor 2 Alpha,Colony-Stimulating Factor, Mast-Cell,Colony-Stimulating Factor, Multipotential,Erythrocyte Burst-Promoting Factor,IL-3,Mast-Cell Colony-Stimulating Factor,Multipotential Colony-Stimulating Factor,P-Cell Stimulating Factor,Eosinophil-Mast Cell Growth-Factor,Hematopoietin-2,Burst Promoting Factor, Erythrocyte,Colony Stimulating Factor, Mast Cell,Colony Stimulating Factor, Multipotential,Eosinophil Mast Cell Growth Factor,Erythrocyte Burst Promoting Factor,Hematopoietin 2,Interleukin 3,Multipotential Colony Stimulating Factor,P Cell Stimulating Factor
D009190 Myelodysplastic Syndromes Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA. Dysmyelopoietic Syndromes,Hematopoetic Myelodysplasia,Dysmyelopoietic Syndrome,Hematopoetic Myelodysplasias,Myelodysplasia, Hematopoetic,Myelodysplasias, Hematopoetic,Myelodysplastic Syndrome,Syndrome, Dysmyelopoietic,Syndrome, Myelodysplastic,Syndromes, Dysmyelopoietic,Syndromes, Myelodysplastic
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004921 Erythropoietin Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000740 Anemia A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN. Anemias
D000971 Antineoplastic Combined Chemotherapy Protocols The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form. Anticancer Drug Combinations,Antineoplastic Agents, Combined,Antineoplastic Chemotherapy Protocols,Antineoplastic Drug Combinations,Cancer Chemotherapy Protocols,Chemotherapy Protocols, Antineoplastic,Drug Combinations, Antineoplastic,Antineoplastic Combined Chemotherapy Regimens,Combined Antineoplastic Agents,Agent, Combined Antineoplastic,Agents, Combined Antineoplastic,Anticancer Drug Combination,Antineoplastic Agent, Combined,Antineoplastic Chemotherapy Protocol,Antineoplastic Drug Combination,Cancer Chemotherapy Protocol,Chemotherapy Protocol, Antineoplastic,Chemotherapy Protocol, Cancer,Chemotherapy Protocols, Cancer,Combinations, Antineoplastic Drug,Combined Antineoplastic Agent,Drug Combination, Anticancer,Drug Combination, Antineoplastic,Drug Combinations, Anticancer,Protocol, Antineoplastic Chemotherapy,Protocol, Cancer Chemotherapy,Protocols, Antineoplastic Chemotherapy,Protocols, Cancer Chemotherapy
D016178 Granulocyte-Macrophage Colony-Stimulating Factor An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. CSF-GM,Colony-Stimulating Factor, Granulocyte-Macrophage,GM-CSF,Histamine-Producing Cell-Stimulating Factor,CSF-2,TC-GM-CSF,Tumor-Cell Human GM Colony-Stimulating Factor,Cell-Stimulating Factor, Histamine-Producing,Colony Stimulating Factor, Granulocyte Macrophage,Granulocyte Macrophage Colony Stimulating Factor,Histamine Producing Cell Stimulating Factor,Tumor Cell Human GM Colony Stimulating Factor
D016179 Granulocyte Colony-Stimulating Factor A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. Colony-Stimulating Factor, Granulocyte,G-CSF,Myeloid Growth Factor,Colony Stimulating Factor, Granulocyte,Factor, Granulocyte Colony-Stimulating,Factor, Myeloid Growth,Granulocyte Colony Stimulating Factor,Growth Factor, Myeloid

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