Serum Soluble CD27, but Not Thymidine Kinase, Is an Independent Prognostic Factor for Outcome in Indolent Non-Hodgkin’s Lymphoma

Abstract

Non-Hodgkin’s lymphoma (NHL) forms a heterogeneous group of diseases. Tumor markers may help to identify high-risk patients who might benefit from more aggressive therapy. Serum soluble CD27 (sCD27) and thymidine kinase (TK) are potentially valuable markers, since sCD27 has previously been shown to be related to tumor load and TK to proliferation of malignant cells. We determined serum sCD27, TK, beta-2-microglobulin (β₂M) and lactic dehydrogenase (LD) levels at diagnosis in 79 lymphoma patients and correlated these parameters with the stage of disease, the International Prognostic Index (IPI) score and survival. Receiver operator characteristic (ROC) curve analysis showed an excellent ability for sCD27 to discriminate between low- and high-stage disease (p < 0.001), especially in indolent lymphomas. No discriminative value for TK, β₂M or LD was found. For aggressive NHL, sCD27, TK, β₂M and LD did predict survival in the univariate analyses. However, LD was found to be the most independent prognostic factor in a multivariate Cox regression model. In indolent lymphomas, sCD27 proved to be a powerful marker to predict progression-free survival (p = 0.008). Taken together, the results of the ROC curve and survival analysis suggest that substitution of LD by sCD27 in the IPI may be considered for indolent lymphomas to enhance the prognostic value. A study in a larger cohort of patients is required to validate this approach.

Serum thymidine kinase 1 concentration as a prognostic factor of chemotherapy-treated non-Hodgkin’s lymphoma patients

“…A close relationship between prognosis and STK activity level was found, that is, to the clinical stage and pathological grade. STK activity was also found to be a prognostic factor to evaluate the survival time (Gronowitz et al 1983;Rehn et al 1991;Suki et al 1995;Poley et al 1997;Kok et al 2003;Zhang et al 2001). In patients with chronic lymphatic leukemia (CLL), the STK activity level was related to clinical stage and other prognostic factors under the conditions of the provision of prognostic information (Gronowitz et al 1983;Rehn et al 1991;Suki et al 1995;Poley et al 1997).…”

“…In patients with chronic lymphatic leukemia (CLL), the STK activity level was related to clinical stage and other prognostic factors under the conditions of the provision of prognostic information (Gronowitz et al 1983;Rehn et al 1991;Suki et al 1995;Poley et al 1997). However, it remains unclear whether STK activity can be used to predict the therapeutic eVect or long-term survival times in this type of cancer (Kok et al 2003). Recently, antibodies against TK1 have been developed and used for determination of TK1 concentration in serum (STK1) (He et al 1996;Wu et al 2003).…”

Soluble CD22 as a tumor marker for hairy cell leukemia

“…A wide variety of soluble receptors and antigens have been reported associated with malignancies, including soluble granulocyte-monocyte colony-stimulating factor receptor in acute myelogenous leukemia (AML), 1 soluble CD20 in non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and Hodgkin disease (HD), 2,3 soluble CD25 (soluble interleukin-2 receptor alpha or sTac) in CD25 ϩ T-and B-cell malignancies, solid tumors and in autoimmune disorders, [4][5][6] soluble CD27 in indolent NHL, 7 soluble CD30 in autoimmune disorders 8 and in HD, 9,10 soluble CD40 in multiple myeloma (MM), CLL, mantle cell lymphoma (MCL), and AML, 11 soluble CD44 in NHL and early CLL, 12 soluble CD52 in CLL, 13 soluble CD80 in CLL and MCL, 14 soluble CD86 in MM and NHL, 15,16 soluble CD137 in leukemias and lymphomas, 3,17 soluble CD138 in MM 18 and CLL, 19 soluble CD307 (IRTA2, FcRH5) in hairy cell leukemia (HCL), MM, CLL, and MCL, 20,21 beta 2 -microglobulin in HD, MM, and solid tumors, [22][23][24] soluble tumor necrosis factor receptor in NHL, 25 and soluble mesothelin in mesotheliomas. 26 However, none of these markers is routinely used in the management of patients with B-cell malignancies.…”

CD27-CD70 interactions in the pathogenesis of Waldenström macroglobulinemia

“…In addition to its functional role, these studies also suggest that sCD27 may serve as a faithful marker of disease in patients with WM. Notably, our data also suggest that targeting CD70 and sCD27-CD70 interactions may produce important clinical benefits for patients with WM, and possibly other B-cell malignancies such as chronic lymphocytic leukemia (CLL) and Hodgkin disease (HD), as well as autoimmune-related disorders wherein either elevated sCD27 levels have been reported [24][25][26][27][28][29][30] or the presence of excess MCs has been observed in association with lymphoid aggregates. [31][32][33][34] Investigation, therefore, of a role for sCD27-CD70 interactions among lymphocytes and MCs in these disorders would appear warranted.…”