Toxicity of cytarabine constant rate infusion in dogs with high-grade non-Hodgkin lymphoma with bone marrow or central nervous system involvement

Objective: Cytarabine, a cell-cycle phase-specific antimetabolite, has been reported to improve outcomes in dogs with bone marrow (BM) or central nervous system (CNS) lymphoma involvement receiving combination chemotherapy. The objective of this study was to evaluate the incidence and severity of toxicity of cytarabine constant rate infusion (CRI) in dogs with high-grade non-Hodgkin lymphoma. Methods: Medical records of canine lymphoma patients with confirmed or suspected BM (group 1) or CNS (group 2) involvement, treated with a modified cyclophosphamide, epirubicin, vincristine and prednisolone protocol, including a single dose of cytarabine given as CRI, were reviewed and adverse events graded. Results: Twenty-six dogs were included. Gastrointestinal toxicity occurred in 17 dogs (65.3%), with 5 (19.2%) experiencing grade III or IV toxicity. Neutropenia occurred in nine dogs (34.6%), but was grade I or II in most cases. Three dogs (11.5%) had thrombocytopenia: one grade III and two grade IV. Four dogs (15.3%) experienced increases in alanine amino transferase: one each grade I and II and two grade III. Five dogs (19.2%) required hospitalisation to manage toxicity after completing cytarabine CRI, and haematological toxicity resulted in treatment delays in five dogs (median delay of 4 days, range: 3-7 days). Conclusion: Our findings suggest that gastrointestinal toxicity should be expected in lymphoma patients undergoing cytarabine CRI.