Thymidine kinase levels correlate with prognosis in aggressive lymphoma and can discriminate patients with a clinical suspicion of indolent to aggressive transformation

Serum levels of thymidine kinase 1 (TK1), an enzyme involved in the G1-S phase of the cell cycle, have been previously shown to correlate with the prognosis of lymphoid malignancies. We hypothesized that TK1 levels will be higher in aggressive, compared to indolent lymphoproliferative, malignancies and this may serve as a marker of transformation from an indolent to aggressive disease. We analyzed serum from 182 patients and correlated the findings with the type of malignancy and prognosis; we further compared the TK1 levels of 31 patients with a proven transformation and 34 patients with clinically suspected transformation that was eventually deferred. The mean TK1 levels of patients with indolent and aggressive disease was 18.9±3.3 and 39.8±3.3 U/l respectively (p0.001). Among patients with aggressive disease, low TK1 levels correlated with improved survival (p=0.008). TK1 levels16.6 U/l predicted transformation from indolent to aggressive disease (sensitivity of 95%, specificity of 76%, negative predictive value (NPV) of 96% and positive predictive value (PPV) of 69%). A regression analysis showed that only TK1 levels were significant (relative risk (RR)=1.03 for each unit, confidence interval (CI)=1-1.05; p=0.015) for diagnosing a true transformation. In conclusion, TK levels are useful in assessing prognosis, especially in aggressive lymphoproliferative diseases. Moreover, TK levels are adequate in discriminating cases of indolent lymphoma that transformed to an aggressive disease from patients with no proven transformations. This tool provides the clinician a novel method to distinguish between symptomatic patients utilizing a simple test and may lessen the need for aggressive or invasive measures of investigation.