Recombinant human granulocyte colony-stimulating factor accelerates hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.
We studied whether treatment of dogs with recombinant human granulocyte colony-stimulating factor (rhG-CSF), after 920 cGy total body irradiation (TBI) and transplantation of 3.3 +/- 1.0 x 10(8) bone marrow cells per kilogram from a DLA-identical littermate, accelerated hematopoietic recovery and influenced the incidence of subsequent marrow graft failure or graft-versus-host disease (GVHD). Ten animals were treated with 100 micrograms rhG-CSF/kg/d from days 1 through 10 after TBI. Results were compared with those of historical control of 14 dogs not administered rhG-CSF. Neither group of dogs received GVHD prophylaxis. The median time to recovery of 1,000 neutrophils/mm3 was 8 days for dogs administered rhG-CSF compared with 14 days in controls (logrank test: P less than .03). The median time to reach 100 monocytes/mm3 was 17 days in G-CSF-treated dogs compared with 49 days in controls (P less than .002). The median time to attain 500 lymphocytes/mm3 was 15 days versus 31 days, respectively (P less than .01). The median time to reach 20,000 platelets/mm3 was 26 versus 20 days (P = .68). Graft failure occurred in 1 of 10 G-CSF-treated dogs versus 2 of 14 controls (two-tailed Fisher's exact test: P = 1.00). GVHD was seen in 4 of 9 rhG-CSF-treated dogs compared with 1 of 12 controls (P = .12). Two G-CSF-treated dogs died of GVHD versus none of the controls (P = .17). No unusual toxicities were seen in dogs receiving rhG-CSF. In summary, rhG-CSF significantly accelerated recovery of neutrophils, monocytes, and lymphocytes after DLA-identical littermate marrow transplantation without altering platelet recovery. Graft failure was not seen more often than in controls, but there was a trend toward an increased incidence of GVHD.
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
Hackman
R
R
Mori
M
M
Souza
L M
LM
Appelbaum
F R
FR
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D003115:Colony-Stimulating Factors / Q000276:immunology / Q000494:pharmacology*; D003429:Cross Reactions; D004285:Dogs; D005260:Female; D006084:Graft Rejection / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D015994:Incidence; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; C039692:histocompatibility antigen DLA; D016179:Granulocyte Colony-Stimulating Factor