Use of Recombinant Canine Granulocyte Colony‐Stimulating Factor to Decrease Myelosuppression Associated with the Administration of Mitoxantrone in the Dog

Abstract

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.

Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor

“…In dogs with cyclic haematopoiesis, administration of rcG‐CSF decreased the severity of neutrophil cycles (Mishu et al ., 1992). Treatment with rcG‐CSF was also shown to decrease the duration and severity of myelosuppression associated with administration of mitoxantrone (Ogilvie et al ., 1992).…”

“…Sources of G‐CSF production include activated macrophages, endothelial cells and fibroblasts (Groopman et al ., 1989). In addition to increasing total numbers of neutrophils, G‐CSF also enhances neutrophil function, including chemotaxis, antibody dependent cellular cytotoxicity, immunoglobulin A‐mediated phagocytosis, and superoxide production (Nicola, 1989; Glaspy & Golde, 1992; Ogilvie et al ., 1992).…”

“…Indeed, the use of G‐CSF has had a significant positive impact on outcomes following chemotherapy, primarily by ameliorating neutropenia and associated complications. In veterinary medicine, rcG‐CSF has also been evaluated for use in management of chemotherapy‐induced neutropenia (Ogilvie et al ., 1992). Treatment of healthy dogs with rcG‐CSF was shown to effectively sustain an increased neutrophil count without inducing adverse effects (Zinkl et al ., 1992).…”

Febrile Neutropenia

“…Although the gene mutation that causes TNS has been identified, the underlying mechanism by which this mutation leads to decreased release of segmented neutrophils into circulation remains unknown. [74][75][76][77][78] It has been demonstrated effective in dogs to accelerate recovery from neutropenia resulting from Parvovirus, chemotherapeutics, and cyclic hematopoiesis. These antibodies cross-react with and neutralize canine G-CSF, which causes a chronic neutropenia.…”

“…48 of this human protein to dogs may lead to the development of antibodies against rhG-CSF. 64,76,77,79 Some questions remain regarding its safety, however. 73 Recombinant canine G-CSF (rcG-CSF) was developed and has been used effectively to increase granulopoiesis in dogs and cats.…”