title: Repeated lentivirus-mediated granulocyte colony-stimulating factor administration to treat canine cyclic neutropenia.
abstract: Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by recurrent neutropenia, and is treated by repeated injections of recombinant granulocyte colony-stimulating factor (rG-CSF). As dose escalation of lentivirus may be clinically necessary, we monitored the outcome of four sequential intramuscular injections of G-CSF-lentivirus (3 × 10(7) IU/kg body weight) to a normal dog and a gray collie. In the normal dog absolute neutrophil counts were significantly increased after each dose of virus, with mean levels of 27.75 ± 3.00, 31.50 ± 1.40, 35.05 ± 1.68, and 43.88 ± 2.94 × 10(3) cells/μl, respectively (p<0.001), and elevated neutrophil counts of 31.18 ± 7.81 × 10(3) cells/μl were maintained for more than 6 years with no adverse effects. A gray collie dog with a mean count of 1.94 ± 1.48 × 10(3) cells/μl received G-CSF-lentivirus and we observed sustained elevations in neutrophil levels for more than 5 months with a mean of 26.00 ± 11.00 × 10(3) cells/μl, significantly increased over the pretreatment level (p<0.001). After the second and third virus administrations mean neutrophil counts of 15.80 ± 6.14 and 11.52 ± 4.90 × 10(3) cells/μl were significantly reduced compared with cell counts after the first virus administration (p<0.001). However, after the fourth virus administration mean neutrophil counts of 15.21 ± 4.50 × 10(3) cells/μl were significantly increased compared with the previous administration (p<0.05). Throughout the nearly 3 years of virus administrations the dog gained weight, was healthy, and showed neutrophil counts significantly higher than pretreatment levels (p<0.001). These studies suggest that patients with cyclic and other neutropenias may be treated with escalating doses of G-CSF-lentivirus to obtain a desired therapeutic neutrophil count.
authors: Department of Pediatrics, University of Washington, Seattle, 98109, USA.
authors: Ofer
authors: O
authors: Yanay
authors: David C
authors: DC
authors: Dale
authors: William R A
authors: WR
authors: Osborne
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics / Q000628:therapy*; D004285:Dogs; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D009503:Neutropenia / Q000235:genetics / Q000628:therapy / Q000662:veterinary*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor