Kinetic response of human marrow myeloid progenitor cells to in vivo treatment of patients with granulocyte colony-stimulating factor is different from the response to treatment with granulocyte-macrophage colony-stimulating factor.
We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) induced sustained increases in cycling of myeloid progenitors in patients with sarcoma. However, decreased proliferation of these cells to a slow- or noncycling state, below pretreatment levels, occurred within 1 to 2 days and maintained for at least 1 week after discontinuation of GM-CSF. To assess possible biological differences in GM-CSF and granulocyte (G)-CSF in such kinetic effects, we evaluated cycling status of marrow progenitors before, during, and after administration of recombinant human G-CSF (5 micrograms/kg/d subcutaneously [s.c.]) to six patients with sarcoma for 8 days. On the last (8th) day of G-CSF treatment, cycling rates of colony-forming units-granulocyte/macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and multipotent colony-forming units (CFU-GEMM) were enhanced 1.5- to 1.9-fold, to values of 40 +/- 10% to 58 +/- 5%. In sharp contrast to patients receiving GM-CSF, however, progenitor cells from patients off G-CSF treatment for 2 to 4 days were still rapidly proliferating. These differences in proliferative kinetics may be of use for design of clinical trials to efficaciously utilize these growth factors.
Broxmeyer
H E
HE
Department of Medicine (Hematology/Oncology, Indiana University School of Medicine, Indianapolis 46202-5121.
Benninger
L
L
Patel
S R
SR
Benjamin
R S
RS
Vadhan-Raj
S
S
D001853:Bone Marrow / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007279:Injections, Subcutaneous; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012509:Sarcoma / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor