Abstract

Abstract Background: Diffuse large-cell B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphomas (NHL) that accounts for approximately 25% of the patients. Earlier studies demonstrated the prognostic value of serum thymidine kinase 1 (STK1) activity determinations in different hematological malignancies. To date, the prognostic value of STK1 protein concentration in patients with DLBCL treated with R-CHOP has not been investigated. The purpose of this retrospective study was to determine the value of high TK levels on Overall survival among DLBCL patients treated with R-CHOP as first-line treatment. Materials and Methods: The study included 146 patients diagnosed with DLBCL between 2010 and 2016 from the Uppsala-Umeå Comprehensive Cancer Consortium (U-CAN). All patients included were treated using the standard chemotherapy regimen R-CHOP. Serum samples were collected at the time of diagnosis, during the treatment, 1 year after treatment, and after relapse. Non-infected and apparently healthy persons, matched to the DLBCL patients (57 males and 88 females), served as controls. The TK1 protein levels in all serum samples were determined by using AroCell TK 210 ELISA (AroCell AB, Sweden). The TK1 protein concentration was expressed as μg/L. Results: The TK1 concentrations in sera from DLBCL patients before treatment were significantly higher compared to the concentrations in healthy individuals, median 0.44 μg/L (IQ range 0.22 to 1.06 μg/L) vs. median 0.22 μg/L (IQ range 0.18 to 0.29 μg/L, P<0.00001). Serum TK1 was also significantly higher in patients with more advanced stages (P<0.00001), higher IPI (P<0.00001), and in patients with B-symptoms (P<0.0001). Patients with STK1 protein levels below the cut-off value (0.45 μg/L) had significantly better OS and DFS (P=0.04 and P=0.0006, respectively) compared to patients with STK1 concentration above the cut-off. In multivariate analyses, dichotomized S-TK1 measurements before treatment were found to be significant for the risk of relapse in combination with either aaIPI or IPI (p<0.01). Conclusions: These results confirmed that STK1 concentration correlates with risk factors such as tumor burden, Ann Arbor stage, and IPI. In conclusion, patients with high TK1 concentrations at the time of diagnosis have short overall survival and STK1 concentrations are apparently a prognostic indicator for survival in patients treated with modern chemo-immunotherapy. Citation Format: Kiran Jagarlamudi, Gustaf Hedström, Per Venge, Staffan Eriksson, Daniel Molin, Gunilla Enblad. The Prognostic value of serum TK1 protein determinations using AroCell TK210 ELISA in DLBCL patients treated with R CHOP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5210.

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