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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1732-1737
Elevated Serum Thymidine Kinase Levels Identify a Subgroup at High
Risk of Disease Progression in Early, Nonsmoldering Chronic
Lymphocytic Leukemia
Michael Hallek,
Irmgard Langenmayer,
Christoph Nerl,
Wolfgang Knauf,
Hermann Dietzfelbinger,
Dagmar Adorf,
Marianne Ostwald,
Raymonde Busch,
Ingrid Kuhn-Hallek,
Eckhard Thiel, and
Bertold Emmerich
From the Medizinische Klinik, Abteilung für Hämatologie
und Onkologie, Klinikum Innenstadt,
Ludwig-Maximilians-Universität München; Städtisches
Krankenhaus München Schwabing; I. Medizinische Klinik und
Poliklinik, Abteilung für Hämatologie und Onkologie,
Institut für Medizinische Statistik und Epidemiologie, Technische
Universität München; Medizinische Klinik III mit
Schwerpunkt Hämatologie, Onkologie und Transfusionsmedizin,
Universitätsklinikum Benjamin Franklin der Freien
Universität Berlin, Germany.
Chronic lymphocytic leukemia (CLL) shows a remarkably heterogeneous
clinical outcome; survival ranges from several months in advanced
stages to more than 10 years in early stages. The Binet and Rai staging
systems distinguish three major prognostic subgroups, but do not
accurately predict the individual risk of disease progression in early
CLL (Binet stage A or Rai stage 0 to II). Because most newly diagnosed
CLL patients present with early disease, it seems desirable to search
for additional prognostic factors to identify early CLL patients at
high risk of rapid progression. It has been shown that elevated serum
thymidine kinase (s-TK) levels predict disease progression in CLL.
Therefore, this study aimed to assess the prognostic value of s-TK in
122 previously untreated patients with Binet stage A CLL (mean age ± SD, 58.7 ± 8.5 years). In univariate analyses, 18 of the 22 parameters investigated predicted progression-free survival (PFS). In a
stepwise multiple regression analysis, only three parameters provided
independent prognostic information on PFS: s-TK greater than 7.1 U/L;
presence of lymphadenopathy; and white blood cell (WBC) count greater
than 75,000/µL. When added to the classification of smoldering versus nonsmoldering CLL, s-TK levels separated two groups within the group of
nonsmoldering stage A patients: patients with s-TK values greater than
7.1 U/L had a median PFS of 8 months, whereas patients with s-TK values  7.1 U/L expected a much longer PFS (49 months; P < .001),
similar to smoldering CLL (42 months). The results demonstrate that
s-TK is a prognostic parameter that adds independent prognostic
information to the definitions of smoldering and nonsmoldering CLL in
Binet stage A.
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