Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia.

The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/microliter) measured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 19.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values < 5 U/microliter). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK > 38 U/microliters, a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK < 38 U/microliter (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK > 38 U/microliters and 9/69 (13%) of those with lower levels at diagnosis (P < 0.0001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.