title: Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes--a phase I/II trial.
abstract: In a phase I/II study, 11 patients with myelodysplastic syndromes (MDS) and severe transfusion-dependent cytopenia were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to investigate the effects of rhGM-CSF on normal hematopoiesis and leukemic cells. The treatment schedule included dose escalation from 15 micrograms/m2 to 150 micrograms/m2 administered by continuous intravenous (IV) infusion for seven to 14 days and was repeated after a two-week treatment-free interval. The blood leukocyte counts increased dose dependently by 130% to 1,800% in ten patients; a rise of monocytes and eosinophils occurred in seven and six patients, respectively. No sustained increase in reticulocytes or platelets was observed. Lymphocyte counts increased in all patients affecting both T-helper and T-suppressor cells; however, the lymphocytes were not activated as analyzed by the expression of the interleukin-2 receptor. In four of the patients, all with greater than 14% blast cells in the bone marrow, the percentage of bone marrow blast cells increased during treatment with rhGM-CSF. Cytogenetic data indicated induction of both proliferation and differentiation of the leukemic clones by rhGM-CSF. Toxic side effects were minor with slight fever, phlebitis at the infusion site, and bone pain in the minority of patients. In conclusion, rhGM-CSF effectively stimulates hematopoiesis in vivo in patients with myelodysplastic syndromes. However, as the leukemic cell population can be stimulated in patients with a higher initial blast cell count, the combination of rhGM-CSF with other differentiation-inducing or cytotoxic agents has to be considered.
authors.affiliation: Department of Hematology, University of Frankfurt, FRG.
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.forename: B
authors.initials: B
authors.lastname: Völkers
authors.forename: J
authors.initials: J
authors.lastname: Greher
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: F
authors.initials: F
authors.lastname: Walther
authors.forename: R
authors.initials: R
authors.lastname: Becher
authors.forename: L
authors.initials: L
authors.lastname: Bergmann
authors.forename: G
authors.initials: G
authors.lastname: Schulz
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor