There is life in the old dog yet: thymidine kinase as predictive marker in diffuse large B-cell lymphoma

Abstract

Th ymidine kinase (TK) was initially described in the early 1950s as an enzyme being critically involved in the salvage pathway for DNA synthesis [1]. While the majority of TK activity that is detectable in serum is associated with the proliferative phase of the cell cycle (G1/S), another mitochondrial isoenzyme, TK2, is independent of the cell cycle. Th e role of serum TK as a prognostic factor in indolent lymphomas including chronic lymphocytic leukemia is well established, and has been extensively validated in several prospective clinical trials [2,3]. It has also been shown that high levels of TK are associated with advanced disease stage. In addition, TK can also be utilized as a predictive marker for survival, and high levels of TK before treatment were linked to inferior survival data in patients with newly diagnosed follicular lymphoma and peripheral T-cell lymphoma (PTCL) [4,5]. In this issue of Leukemia and Lymphoma , Suzuki et al . evaluated the predictive power of TK in diff use large B-cell lymphoma (DLBCL) [6]. Th e latter subtype of lymphoma has rarely been studied with respect to this particular parameter. Furthermore, this study exclusively included data obtained from treatment-naive patients homogeneously treated with the rituximab-containing regimen, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). Th is is indeed one of the few analyses that has evaluated an established marker such as TK in the rituximab era of chemoimmunotherapy. Here it is noteworthy that TK showed independent predictive value in a multivariate analysis that included other well-established prognostic markers such as age, performance status, revised International Prognostic Index (R-IPI), bulky mass and B symptoms. Since high TK activity correlated with inferior clinical response as well as inferior progression-free and overall survival after treatment with R-CHOP, the authors suggest that this is most likely to be due to a more malignant tumor phenotype present in a highly proliferative status (G1/S phase) of the lymphoma. Th is observation is of critical clinical importance, because alternative treatment strategies, including autologous or allogeneic transplant, should be considered in patients with high-risk DLBCL with high TK levels. Nevertheless, what to off er these high-risk patients still remains a challenge, since recent trials have been disappointing for young patients with high-risk DLBCL, at least in regard to high-dose chemo