title: Recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy: a phase Ib trial.
abstract: We evaluated the toxic, hematopoietic, and immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). The rHuGM-CSF was administered at doses up to 50 micrograms/kg by daily 2-hour intravenous infusions to 11 patients with advanced malignancy. It induced dose-related increases in cells of the myeloid series, but it had no significant effect on reticulocyte or platelet counts. Bone marrow cellularity increased with higher doses of rHuGM-CSF, but there was a dose-related decrease in the number of colony-forming units--granulocyte-monocyte--and colony-forming units--granulocyte-erythrocyte-monocyte-megakaryocyte--per 10(5) bone marrow cells. The rHuGM-CSF caused transient increased expression of CD11b and CD16 on granulocytes but increased expression of HLA-DR and decreased expression of the high-affinity Fc receptor on monocytes and no change in monocyte production of H2O2. Thus, rHuGM-CSF has potent effects on granulocyte, eosinophil, and monocyte numbers in the peripheral blood and bone marrow. In addition, it enhances the expression of monocyte and granulocyte activation-associated surface markers.
authors: Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research Facility, MD 21701.
authors: R G
authors: RG
authors: Steis
authors: L A
authors: LA
authors: VanderMolen
authors: D L
authors: DL
authors: Longo
authors: J W
authors: JW
authors: Clark
authors: J W
authors: JW
authors: Smith
authors: W C
authors: WC
authors: Kopp
authors: F W
authors: FW
authors: Ruscetti
authors: S P
authors: SP
authors: Creekmore
authors: L J
authors: LJ
authors: Elwood
authors: J
authors: J
authors: Hursey
mesh_terms: D000943:Antigens, Differentiation / Q000032:analysis; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D006133:Growth Substances / Q000009:adverse effects / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D016177:Macrophage-1 Antigen; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000943:Antigens, Differentiation; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D006684:HLA-DR Antigens; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor