Review for "Manufacturing Biological Medicines on Demand: Safety and Efficacy of Granulocyte‐Colony Stimulating Factor in a Mouse Model of 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.

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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

Blood ◽

10.1182/blood.v81.1.20.bloodjournal81120 ◽

1993 ◽

Vol 81 (1) ◽

pp. 20-26 ◽

Cited By ~ 1

Author(s):

FG Schuening ◽

FR Appelbaum ◽

HJ Deeg ◽

M Sullivan-Pepe ◽

TC Graham ◽

...

Keyword(s):

Stem Cell ◽

Total Body Irradiation ◽

Stem Cell Factor ◽

Combined Treatment ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Platelet Recovery ◽

Hematopoietic Recovery ◽

Total Body ◽

Stimulating Factor

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.

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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

Blood ◽

10.1182/blood.v74.4.1308.1308 ◽

1989 ◽

Vol 74 (4) ◽

pp. 1308-1313 ◽

Cited By ~ 3

Author(s):

FG Schuening ◽

R Storb ◽

S Goehle ◽

TC Graham ◽

FR Appelbaum ◽

...

Keyword(s):

Total Body Irradiation ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Peripheral Leukocyte ◽

Hematopoietic Recovery ◽

Blood Neutrophils ◽

Leukocyte Counts ◽

Total Body ◽

Marrow Infusion ◽

Stimulating Factor

Abstract 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.

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