PROGNOSTIC RELEVANCE OF SERUM THYMIDINE KINASE IN PRIMARY MYELODYSPLASTIC SYNDROMES - RELATIONSHIP TO DEVELOPMENT OF ACUTE MYELOID-LEUKEMIA

The aim of this study was to evaluate the possible prognostic relevanc e of thymidine kinase serum levels (s-TK), an indirect marker of proli ferative activity, in myelodysplastic syndromes (MDS), S-TK levels wer e monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 2 1 RA with blast excess, RAEB: 15 RAEB in transformation, RAEB-T; 15 ch ronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/mu l) meas ured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 1 9.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values <5 U/mu l). With the only exception of a weak rel ationship 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 o f bone marrow blasts, MDS patients with s-TK >38 U/mu l, a cut-off lev el selected by means of ROC statistical analysis, showed a significant ly shorter survival than those with s-TK <38U/mu l (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute mye loid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK >38 U/mu l 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 patie nts with normal initial values. Multivariate analysis confirmed the in dependent prognostic value of s-TK on both overall survival and risk o f acute transformation. We conclude that s-TK may be an important prog nostic factor in MDS, strongly correlated with development of AML.