Serum thymidine kinase activity: analytical performance, age-related reference ranges and validation in chronic lymphocytic leukemia.

BACKGROUND: To date no age-related reference ranges are available for serum thymidine kinase (TK1) activity. Being a proliferation marker, it may be used as a prognostic marker in malignant diseases, including chronic lymphocytic leukemia (CLL). Our aim was to establish age-specific reference ranges for TK1 and examine its utility as a screening marker in CLL, a disease of the elderly. METHODS: Serum TK1 activity was measured by a competitive chemiluminescent immunoassay in 369 healthy adults and 115 de novo CLL patients. RESULTS: We observed a statistically significant decline in TK1 activity from young (18-35 years) to middle-aged (36-60 years) and further on to elderly (60-86 years) healthy individuals. Age-related reference range was: <30 U/L for young, <25 U/L for middle-aged and <19 U/L for elderly. There was no difference in TK1 activity between the studied healthy men and women. In CLL patients, TK1 activity was the highest in the advanced Rai stages. The area under the receiver operating characteristic curve (ROC-AUC) for TK1 was 0.840 (95% CI: 0.787-0.892), for differentiating CLL patients from age and sex matched healthy controls, with a cut-off value of 10.5 U/L (sensitivity: 80.9%, specificity: 73.4%). TK1 was significantly elevated in CD38+/Zap70+ CLL patients, and showed significant correlation with WBC and absolute B-cell count. CONCLUSION: In the healthy, serum TK1 activity does not differ in the two sexes but declines significantly with age. As such, use of age-related reference ranges is warranted, especially when evaluating CLL patients who generally belong to the elderly age group

CLL patient characteristics.

<p>CLL patient characteristics.</p

Age-related frequency distributions of serum thymidine kinase activity in age groups 18–35 years (A), 35–60 years (B) and 60–86 years (C).

<p>Box and whisker plots showing significant difference of serum TK activity in the studied age groups (D).</p

Serum thymidine kinase activity of CLL patients upon presentation in different prognostic groups.

<p>Serum thymidine kinase activity of CLL patients upon presentation in different prognostic groups.</p

Receiver operating characteristic (ROC) analysis of serum thymidine kinase activity for differentiating all CLL patients (A) and Rai 0 CLL patients (B) from age and sex matched healthy controls.

<p>AUC, area under the receiver operating characteristic curve.</p

Comparison of serum thymidine kinase activity in de novo CLL patients in Rai 0, Rai 1 and Rai 2-3-4 clinical stages with the age and sex matched healthy cohort.

<p>Comparison of serum thymidine kinase activity in de novo CLL patients in Rai 0, Rai 1 and Rai 2-3-4 clinical stages with the age and sex matched healthy cohort.</p

Inter-assay and Intra-assay precision and accuracy for serum thymidine kinase activity of QC1 and QC2 samples.

<p>SD, standard deviation; %CV, percent coefficient of variation; %DFN, percent deviation from nominal value.</p

Flow diagram of study population.

<p>Flow diagram of study population.</p