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Effects of recombinant canine stem cell factor, a c-kit ligand, and
recombinant granulocyte colony-stimulating factor on hematopoietic recovery
after otherwise lethal total body irradiation
FG Schuening, FR Appelbaum, HJ Deeg, M Sullivan-Pepe, TC Graham, R Hackman, KM Zsebo and R Storb
Clinical Research Division, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis
were studied in normal dogs and in dogs given otherwise lethal total body
irradiation (TBI) without marrow transplant. Results were compared with
previous and concurrent data with recombinant granulocyte
colony-stimulating factor (rG-CSF). Four normal dogs received 200
micrograms rcSCF per kilogram body weight daily either by continuous
intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection
in two divided doses for 20 days (n = 2). All dogs showed at least a
twofold increase in peripheral blood neutrophil counts starting
approximately 7 days after the initiation of treatment. Hematocrit level
and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts
were not elevated. Marrow sections after rcSCF treatment showed
panhyperplasia. The only toxicity was facial edema during the first few
days of rcSCF administration, presumably caused by mast cell stimulation.
Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co
sources. They were given no marrow infusion and received 200
micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2
hours of TBI. Five of the 10 dogs showed complete and sustained
hematopoietic recovery and survived as compared with 1 of 28 control dogs
not receiving growth factor (P < .005). RcSCF treatment allowed for
hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but
in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar
to those obtained with rG-CSF. The rate of neutrophil recovery in
rcSCF-treated dogs after 400 cGy TBI was not different from that of
rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster
(P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and
rcG-CSF after 500 cGy TBI did not result in strongly improved survival as
compared with results obtained with either factor alone.
Volume 81,
Issue 1,
pp. 20-26,
01/01/1993
Copyright © 1993 by The American Society of Hematology
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