Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma

Abstract

Background: Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis.

Objectives: Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in dogs with lymphoma.

Animals: Ninety-seven client-owned dogs with naive or relapsed lymphoma and 23 healthy dogs.

Methods: Prospective study. Serum TK1 activity measured by refined ELISA-based method (DiviTum assay, Biovica International) before treatment, at clinical response, and every 4 weeks until relapse or last follow-up.

Results: Serum TK1 activity was ≤20 Du/L in 96% (22/23) of healthy dogs. Pretreatment sTK1 activity was >20 Du/L in 88% (85/97) dogs with lymphoma. At clinical response, sTK1 activity was significantly lower in dogs with complete (CR, n = 36) versus partial (PR, n = 29) response (P < .0001). Sensitivity (Se) and specificity (Sp) of sTK1 activity for detecting nonfully responders were 76% and 100%, respectively, with cutoff of 119.5 Du/L (AUC, 0.90; 95%-CI, 0.81-0.98; P < .0001). In dogs with CR, a 5-fold increase in sTK1 activity at a 4-week interval predicted relapse at the subsequent 4-week assessment with a Se 50% and Sp 94% (AUC, 0.72; 95%-CI, 0.55-0.90; P = .02). An increase of sTK1 activity (>2.7-fold value measured at clinical response) predicted relapse at subsequent 4-week assessment with a Se 61% and Sp 88% (AUC, 0.79; 95%-CI, 0.64-0.95; P = .004).

Conclusions and clinical importance: Monitoring sTK1 activity could help to detect complete responders and early disease progression in dogs with lymphoma.

Keywords: DiviTum assay; chemotherapy; monitoring; remission.