Serum levels of endogenous and exogenous granulocyte colony-stimulating factor after autologous blood stem cell transplantation.
Although the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhances myeloid engraftment and reduces infectious morbidity after autologous and allogeneic bone marrow transplantations, the effect of rhG-CSF on neutrophil recovery in autologous blood stem cell transplantation (ABSCT) is controversial. We previously demonstrated that a low dose, delivered subcutaneously, of rhG-CSF (50 micrograms/m2) accelerates neutrophil recovery in ABSCT, but the optimal dosage of rhG-CSF is not known. To elucidate the effect of rhG-CSF on neutrophil recovery, we determined serum levels of endogenous and exogenously administered G-CSF in 24 patients receiving ABSCT. Of these, five received bolus subcutaneous injection of 50 micrograms/m2 rhG-CSF, 10 received 150 micrograms/m2, and nine received no rhG-CSF. Endogenous G-CSF levels rose immediately after ABSCT, and an inverse correlation was found between the serum level of G-CSF and the absolute neutrophil count (r = -0.73, p < 0.01). The pre-dose level in patients receiving rhG-CSF rose gradually, reaching a maximum between days 3 and 6. The level gradually decreased as the neutrophil count began to rise, even through administration of the same dose of rhG-CSF continued. Pharmacokinetic data showed that the half-life of elimination of G-CSF (t1/2) exceeded 15 hours during severe neutropenia but decreased during the recovery of neutrophils. These observations suggest that neutrophils provide a negative feedback mechanism for clearing G-CSF from the circulation. Pre-dose levels of G-CSF in patients receiving 50 micrograms/m2 rhG-CSF reached 10 ng/mL, equivalent to the concentrations used in clonogenic assay in vitro to stimulate myeloid progenitor cells.
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
C
C
Shimazaki
H
H
Uchiyama
N
N
Fujita
S
S
Araki
Y
Y
Sudo
N
N
Yamagata
E
E
Ashihara
H
H
Goto
T
T
Inaba
H
H
Haruyama
D000293:Adolescent; D000328:Adult; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007564:Japan; D007700:Kinetics; D007938:Leukemia / Q000628:therapy; D007958:Leukocyte Count; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D009369:Neoplasms / Q000628:therapy; D009504:Neutrophils; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor