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Effect of recombinant human granulocyte colony-stimulating factor on
hematopoiesis of normal dogs and on hematopoietic recovery after otherwise
lethal total body irradiation
FG Schuening, R Storb, S Goehle, TC Graham, FR Appelbaum, R Hackman and LM Souza
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
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.
Volume 74,
Issue 4,
pp. 1308-1313,
09/01/1989
Copyright © 1989 by The American Society of Hematology
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