Serum deoxythymidine kinase in myelodysplastic syndromes.
BACKGROUND
Previous studies have shown that serum levels of deoxythymidine kinase (sTK) provide useful prognostic information in various malignancies, such as Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma, and acute myeloid leukemia (AML).


METHODS
Using a radioenzyme assay, the authors determined sTK in 146 patients with primary myelodysplastic syndromes (MDS). Morphologic subtypes were refractory anemia (RA) in 18 patients, RA with ring sideroblasts (RARS) in 24, RA with excess of blasts (RAEB) in 41, RAEB in transformation (RAEB/T) in 29, and chronic myelomonocytic leukemia (CMML) in 34.


RESULTS
Enzyme levels ranged from 1.1 to 829 U/microliters. One hundred fifteen (79%) patients had elevated sTK levels (more than 5 U/microliters) at the time of diagnosis. In advanced stages of MDS (RAEB, CMML, and RAEB/T) enzyme activities were higher than in early stages (RA and RARS) (P < 0.05). However, sTK levels were not correlated with the percentage of medullary blast cells. Among other parameters tested, the best correlation with sTK was found for serum lactate dehydrogenase (LDH) activity (r = 0.29; P < 0.0005). As shown by life table analysis, sTK activity at diagnosis provided useful information regarding the prognosis of patients. For patients with sTK levels of less than 10 U/microliters, actuarial survival after 2 years was 65%, compared with 33% for those with enzyme values of 10 U/microliters or greater. The 5-year cumulative survival rates were 34% and 14%, respectively (P < 0.0005). However, sTK levels at diagnosis were not useful for predicting transformation to AML. Nine of 61 (15%) patients with sTK of less than 10 U/microliters had AML develop, whereas 15 of 57 (26%) patients with sTK of 10 U/microliters or greater had disease progress to acute leukemia (chi-square, 1.64; P = 0.2).


CONCLUSIONS
Considering the lack of correlation with bone marrow blasts, the authors conclude that increased sTK levels in MDS are primarily attributable to intramedullary destruction of hematopoietic precursors and do not reflect the leukemic blast cell burden. This appears similar to the ineffective hematopoiesis of vitamin B12 deficiency, which is associated with elevated levels of sTK and LDH. The data suggest that sTK is a prognostic parameter that can be used to predict the survival of patients with MDS. However, multivariate analysis shows that the predictive value of sTK is not superior to that of LDH.
Aul
C
C
Department of Internal Medicine, Heinrich Heine University, Düsseldorf, Germany.
Gattermann
N
N
Germing
U
U
Winkelmann
M
M
Heyll
A
A
Runde
V
V
Schneider
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D013937:Thymidine Kinase / Q000097:blood*
D007770:L-Lactate Dehydrogenase; D013937:Thymidine Kinase