Denileukin diftitox as prophylaxis against graft-versus-host disease in the canine hematopoietic cell transplantation model.
Denileukin diftitox (Ontak) was evaluated in combination with methotrexate (MTX) for preventing acute graft-versus-host disease (GVHD) in dogs given 9.2 Gy of total body irradiation and DLA-nonidentical hematopoietic cell grafts. Six dogs were given denileukin diftitox 9 ,microg/kg/day intravenously (IV) on days 2, 4, 5, 7, 8, and 10, in combination with MTX 0.4 mg/kg/day IV on days 1, 3, 6, and 11 after transplantation. Median survival of the dogs given MTX in combination with denileukin diftitox was 16 days (range, 13-18 days), similar to that of 35 historical controls given MTX alone (median survival, 20 days). Five of the 6 denileukin diftitox-treated dogs had clinical and pathological evidence of 3-system GVHD; 1 dog died of canine herpes virus infection without evidence of GVHD. In conclusion, denileukin diftitox did not prevent, mitigate, or delay acute GVHD in this stringent and predictive (with respect to outcomes in human patients) hematopoietic cell transplantation model.
Mielcarek
Marco
M
Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington, Department of Medicine, Seattle, Washington 98109-1024, USA. mmielcar@fhcrc.org <mmielcar@fhcrc.org>
Georges
George E
GE
Storb
Rainer
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004167:Diphtheria Toxin / Q000008:administration & dosage*; D004285:Dogs; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control* / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006566:Herpesviridae Infections / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage*; D023421:Models, Animal; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D008727:Methotrexate