title: Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.
abstract: We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).
authors.affiliation: The University of Wisconsin, Madison, USA.
authors.forename: F G
authors.initials: FG
authors.lastname: Schuening
authors.forename: C
authors.initials: C
authors.lastname: von Kalle
authors.forename: H P
authors.initials: HP
authors.lastname: Kiem
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: M
authors.initials: M
authors.lastname: Pepe
authors.forename: T
authors.initials: T
authors.lastname: Gooley
authors.forename: T C
authors.initials: TC
authors.lastname: Graham
authors.forename: R C
authors.initials: RC
authors.lastname: Hackman
authors.forename: R
authors.initials: R
authors.lastname: Storb
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000662:veterinary*; D004285:Dogs; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006648:Histocompatibility; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor