Retrospective study of the prognostic role of serum thymidine kinase level in CLL patients with active disease treated with fludarabine

Background: Previous studies have shown that the serum thymidine kinase (TK) level can be used to determine prognosis in patients with lymphoproliferative diseases, but mainly those with multiple myeloma and non-Hodgkin's lymphoma. In patients with chronic lymphocytic leukemia (CLL), TK levels may provide prognostic information independent of stage and other prognostic factors, but it is still unclear whether they can be used to predict the response to treatment and length of survival. Patients and methods: To determine whether TK levels can be used to predict response and survival, we retrospectively examined the serum TK level in 188 previously treated and untreated patients with active or advanced CLL who were then treated with fludarabine alone or in combination with prednisone. The correlation of the TK level with other prognostic features and with outcome was then assessed. Results: Serum TK levels were elevated in 92% of the patients, and the levels proved to associate with previous treatment, stage of disease, and other tumor-burden related features (i.e., white blood cell counts, absolute lymphocyte count, bone marrow cellularity). The levels were also directly associated with indicators of tumor cell turnover (i.e., β2-microglobulin and lactate dehydrogenase levels). Of particular importance, we found that the TK level was a significant prognostic indicator of both response to treatment and survival. Specifically, 83% of patients with a TK level of <10 U/L responded (complete and partial response) to treatment with fludarabine, whereas only 45% of patients with a TK level ≥10 U/l responded to treatment (P < 0.01). This difference was maintained when we separately analyzed untreated and previously treated patients, and in patients divided according to the Binet stage. The TK level also added prognostic information about response to a predictive model based on the hemoglobin and, albumin levels and the extent of prior treatment. Of further importance, the median survival rate in patients with a TK level of <10 U/l was 65%, as opposed to a rate of 22% in patients with a TK level of ≥10 U/l (P = 0.000). Conclusions: The serum TK level in CLL patients provides useful prognostic information regarding both response to therapy and length of survival and should be used in planning appropriate therapy. In particular, patients with a TK level of ≥10 U/l have a poor prognosis and should be considered for aggressive treatment.