Treating Neutropenia in Cats

Neutropenia is common in patients with hematopoietic disorders and immunodeficiency syndromes and can be induced by chemotherapy. Human granulocyte-colony stimulating factor (HuG-CSF) can be used to augment neutrophil levels in cats and dogs; however, long-term use can be associated with neutralizing antibodies and resultant neutropenia. This clinical trial evaluated the efficacy of recombinant feline (Fe) G-CSF as compared with HuG-CSF. Of primary interest was a pegylated form of FeG-CSF (PegFeG-CSF), in which a polyethylene glycol moiety is added to the protein structure to extend half-life and decrease the dosing interval. Daily FeG-CSF doses induced significantly greater neutrophil production than HuG-CSF after the second week of treatment, while weekly PegFeG-CSF dosing induced signficantly higher neutrophil counts and sustained production as compared to FeG-CSF and controls. Peak neutrophil counts induced by PegFeG-CSF were achieved on day 1 posttreatment. When comparing the effects of long-term daily SC administration of FeG-CSF or HuG-CSF, neutrophil counts dramatically increased in all cats during the first week; however, cats treated with FeG-CSF had a more consistent and robust mean increase. All cats treated with HuG-CSF developed neutralizing antibody titers; PegFeG-CSF cats did not. Long-term (1-year) treatment with PegFeG-CSF in FIV-positive and FIV-negative cats resulted in increased neutrophil counts with each treatment cycle. PegFeG-CSF provided the most therapeutic and sustainable rise in neutrophils when compared with FeG-CSF and HuG-CSF, and was not associated with long-term neutropenia caused by neutralizing antibodies.

Commentary

Neutropenia in cats is commonly seen with retroviral (FIV and FeLV) infections, and with cytotoxic therapy. Other causes include parvoviral infection, myelodysplasia, storage diseases, sepsis, and immune-mediated and drug-associated neutropenias. In humans, recommendations for using G-CSF/GM-CSF are complex as clinical benefits are not apparent in all situations, although indications for its use are wide-ranging. PegFeG-CSF may be a major breakthrough in feline medicine. This study provides only pilot data, as few cats were used, not many had neutropenia, and the causes of neutropenia in some were unclear; nevertheless, the data are encouraging. Future larger clinical trials will be needed to determine true clinical efficacy of PegFeG-CSF and whether this could become a viable commercial product for veterinary use.