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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.
AuthorsR G Steis, L A VanderMolen, D L Longo, J W Clark, J W Smith 2nd, W C Kopp, F W Ruscetti, S P Creekmore, L J Elwood, J Hursey
JournalJournal of the National Cancer Institute (J Natl Cancer Inst) Vol. 82 Issue 8 Pg. 697-703 (Apr 18 1990) ISSN: 0027-8874 [Print] United States
PMID2138680 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Differentiation
  • Colony-Stimulating Factors
  • Growth Substances
  • HLA-DR Antigens
  • Macrophage-1 Antigen
  • Receptors, Fc
  • Receptors, IgG
  • Receptors, Leukocyte-Adhesion
  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
Topics
  • Antigens, Differentiation (analysis)
  • Blood Cell Count
  • Bone Marrow (drug effects)
  • Colony-Stimulating Factors (adverse effects, therapeutic use)
  • Drug Evaluation
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocytes (drug effects, immunology)
  • Growth Substances (adverse effects, therapeutic use)
  • HLA-DR Antigens (analysis)
  • Hematopoiesis (drug effects)
  • Humans
  • Macrophage-1 Antigen
  • Monocytes (drug effects, immunology)
  • Neoplasms (therapy)
  • Receptors, Fc (analysis)
  • Receptors, IgG
  • Receptors, Leukocyte-Adhesion (analysis)
  • Recombinant Proteins (adverse effects, therapeutic use)

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