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A 9.5-year-old, male castrated Persian cat was diagnosed with advanced, diffuse, low-grade, epitheliotropic lymphoma of the small intestine based on histopathology of biopsy samples retrieved during endoscopy. The cat was treated with a dose-intense chemotherapeutic protocol comprised of prednisolone acetate (2.5 mg/kg body weight, intramuscularly q 24 hours) and chlorambucil (15 mg/m^sup 2^ [4 mg total dose], per os q 24 hours for 4 days, repeated every 21 days). Due to a dosing error, the first two chlorambucil doses were given 12 hours apart, and clinical signs of neurological disease (consisting of twitching and agitation) began a few hours after the second dose. The neurological signs progressed to severe facial twitching and myoclonus with muscle jerks of the head and limbs, and these were often brought on by noise, movement, or physical restraint. At least two short episodes consistent with tonic-clonic seizures were also observed. Due to the extreme agitation and hyperesthesia displayed by the cat, a complete neurological examination could not be performed. A minimum database consisting of a complete blood count, serum biochemical analysis, and retroviral testing was essentially unremarkable except for a stress-induced leukogram and hyperglycemia. Based on a tentative diagnosis of chlorambucil-induced neurotoxicity, the cat was given an injection of diazepam and treated supportively with intravenous fluids and enteral nutrition via a nasoesophageal feeding tube. Over the following 48 to 72 hours, neurological signs diminished, and oral prednisone and cyproheptadine were initiated. By day 4 (96 hours), the neurological signs had resolved, and a percutaneous gastrostomy tube was placed for ongoing nutritional support. Subsequently, a modified COP (cyclophosphamide-vincristine-prednisone) protocol was to be administered by the referring veterinarian.
Chlorambucil is prescribed for a variety of conditions in feline oncology and as an immunosuppressive agent for immune-mediated dermatological, hematological, and renal conditions. High doses can be associated with an increased potential for myelosuppression and gastrointestinal toxicity, which are the most commonly recognized adverse effects of the drug. Based on this case report, neurotoxicity in the form of myoclonus or tonic-clonic seizures must be considered a potential adverse effect of chlorambucil therapy in veterinary patients. Symptoms resolve with discontinuation of the drug and supportive care.
Chlorambucil is an alkylating agent commonly used in veterinary oncology for conditions including lymphoma. Chlorambucil neurotoxicity has...