In vivo biologic activities of recombinant human granulocyte-macrophage colony-stimulating factor.
We evaluated the biologic effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in 25 patients with malignancy and/or bone marrow failure of diverse etiologies. The continuous infusion of GM-CSF (15 to 500 micrograms/m2/day) elicited marked leukocytosis (2- to 70-fold increase), consisting primarily of neutrophils, eosinophils, and monocytes. Six patients with cytopenias experienced a multilineage response characterized by significant increases in platelet counts and improvement in erythropoiesis. Response in blood counts was accompanied by significant increases in bone marrow cellularity, myeloid:erythroid cell ratios, and frequency of cycling progenitors, indicating an effect at the stem cell level. By premature chromosome condensation analysis, neutrophils from patients with myeloid diseases were found to be derived from normal as well as abnormal clones. Side effects were generally mild and commonly included constitutional symptoms and bone pain. These results indicate that GM-CSF is a significant stimulus for hematopoiesis in vivo and might play an important role in several clinical arenas.
Vadhan-Raj
S
S
Department of Clinical Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Hittelman
W N
WN
Broxmeyer
H E
HE
Keating
M
M
Urdal
D
D
Gutterman
J U
JU
D000328:Adult; D000368:Aged; D000740:Anemia / Q000628:therapy; D001855:Bone Marrow Diseases / Q000628:therapy*; D003115:Colony-Stimulating Factors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D009503:Neutropenia / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000628:therapy
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor