Plasma ammonia concentration after L-asparaginase therapy in 27 dogs with high-grade lymphoma or leukemia

Abstract

Objectives: To establish the occurrence of increased plasma ammonia concentration after L-asparaginase (L-asp) administration in dogs with high-grade lymphoma or leukemia; to identify risk factors for the development of hyperammonemia after L-asp administration; and to determine occurrence of adverse events related to hyperammonemia.

Design: Prospective case controlled study of sequentially enrolled dogs between May 2011 and March 2012.

Setting: A university veterinary teaching hospital.

Animals: Twenty-seven dogs with high-grade lymphoma or leukemia.

Interventions: All dogs received L-asp intramuscularly at a median dose of 400 IU/kg.

Measurements and main results: Plasma ammonia concentrations were measured at baseline, 16 hours, and 48 hours after L-asp therapy. Clinicopathological abnormalities were assessed to determine risk factors for the development of hyperammonemia. Adverse events following L-asp were recorded. Median plasma ammonia concentrations at baseline, 16 hours, and 48 hours were 26 μmol/L (44 μg/dL), 98 μmol/L (166.9 μg/dL), and 67 μmol/L (114 μg/dL), respectively. Median plasma ammonia concentrations at 16 and 48 hours after administration were significantly increased compared to baseline. Six dogs had adverse events following L-asp administration. No significant clinical signs were noted that could clearly be attributed to hyperammonemia. No risk factors for developing hyperammonemia were identified; however, there was a positive correlation between the development of hyperammonemia at 16- and 48-hour time points.

Conclusions: Subclinical hyperammonemia in dogs with lymphoma or leukemia after L-asp administration appears to be common. No risk factors were identified for the development of hyperammonemia after L-asp treatment, and severe adverse events were rare.

Keywords: Elspar; asparaginase; chemotherapy; hyperammonemia; lymphosarcoma; neoplasia.