Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation.
This study was designed to test whether recombinant human G-CSF (rh G-CSF) affects hematopoiesis in normal dogs and, if so, to test the effects of G-CSF in dogs given otherwise lethal total body irradiation (TBI). Rh G-CSF given subcutaneously at 10 or 100 micrograms/kg/d for 14 days to two normal dogs increased peripheral blood neutrophils eight to tenfold and monocytes four to sixfold above controls. Lymphocyte counts remained unchanged at the lower dose and increased threefold at the higher dose of rh G-CSF. No significant changes were observed in eosinophil, platelet, reticulocyte, or hematocrit levels. After 2 weeks of treatment with rh G-CSF, bone marrow displayed myeloid hyperplasia and left-shifted granulocytopoiesis. After discontinuation of rh G-CSF, peripheral leukocyte counts returned to control levels within three days. Five dogs administered 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow infusion or growth factor, all developed profound pancytopenia and died between 17 and 23 days after TBI with infections secondary to marrow aplasia. Four of five dogs treated within two hours after 400 cGy TBI with 100 micrograms rh G-CSF/kg/d subcutaneously twice a day for 21 days showed complete and sustained endogenous hematopoietic recovery. In contrast, five dogs irradiated with 400 cGy TBI and treated with 100 micrograms rh G-CSF/kg/d starting on day 7 after TBI, all died between days 17 and 20 after TBI with infections secondary to marrow aplasia. Rh G-CSF, if administered shortly after irradiation, can reverse the otherwise lethal myelosuppressive effect of radiation exposure.
Schuening
F G
FG
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Storb
R
R
Goehle
S
S
Graham
T C
TC
Appelbaum
F R
FR
Hackman
R
R
Souza
L M
LM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004285:Dogs; D004307:Dose-Response Relationship, Radiation / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008297:Male; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000494:pharmacology; D014916:Whole-Body Irradiation
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor