Vuković, Vojin

Background: Thromboembolism (TE) is one of major causes of morbidity and mortality in patients with malignancy. Pathophysiological connection between TE and inflammation has been established and it is being thoroughly studied recently. The neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) are biomarkers for systemic inflammation and might represent a yet unrecognized risk factor for development of venous thromboembolism in lymphoma patients having in mind chronic inflammatory milieu specific for lymphomas. Aims: We aimed to investigate the association between NLR, PLR and future risk of TE, in a prospective cohort of lymphoma patients receiving chemotherapy. Methods: We prospectively included 630 patients with B cell non Hodgkin lymphoma /indolent and agressive/, T cell non Hodgkin lymphoma and Hodgkin lymphoma who were diagnosed and treated (period 2014-2019.) at the Clinic for Hematology, Clinical Center of Serbia. Data for newly diagnosed patients, who had completed a minimum of one chemotherapy cycle, were collected for venous TE events from time of diagnosis to 3 months after the last cycle of therapy. NLR and PLR were calculated according to the CBC with differential count. TE complications were diagnosed based on clinical examination, laboratory evaluation and radiographic studies (duplex venous ultrasound, contrast-enhanced computed tomography scan, magnetic resonance imaging (MRI)). Response to therapy was assessed according to Cheson criteria. Logistic regression analysis and ROC curve were performed to assess the association of NLR and PLR with TE and therapy response. Cox regression and Kaplan Meier analysis were used to assess overall survival. Results: The mean age in our group of patients was 53 years (range, 18-89 years) while 52.8% were males. Most patients had advanced stage disease: clinical stage III 20.6% and stage IV, 41.5%. A total of 327 patients (51.9%) had aggressive NHL; 175 (27.8%) had indolent NHL; 102 (16.2%) had HL; 26 (4.1%) had T cell NHL. 51 (8.2%) patients developed thromboembolic events. NLR and PLR were significantly higher in TE patients compared to patients without TE (p=0.001 and p=0.002, respectively). The NLR was positively associated with PLR (p<0.001). A positive NLR was considered 3 or higher, while a positive PLR was a ratio of 10 or more. The ROC curve analysis demonstrated acceptable specificity and sensitivity of NLR and PLR in predicting TE. NLR and PLR were found to be prognostic factors for the TE (relative risk [RR] = 2.9, 95% confidence interval [CI] = 1.6-5.3, p=0.001 and RR=2.7, 95% CI =1.4-5.1, p=0.002, respectively) as well as for overall response to therapy (RR=2.7, 95%CI=1.7-5.7, p<0.001 and RR=2.0, 95%CI=1.1-3.4, p=0.015, respectively). Regarding the overall survival, in univariate analysis there was an association of the development of TE and decreased survival, while in multivariate model NLR was found to be an independent risk factor for overall survival in lymphoma patients (HR=1.8, 95%CI=1.1-2.9, p=0.024) (Figure 1). Summary/Conclusion: NLR could represent useful clinical predictor of TE complications in patients with lymphoma without additional costs to the national health systems. Our research showed that NLR is also predictive for response to therapy and overall survival of lymphoma patients. Simplicity, cost effectiveness, and rapid turn around qualify this new tool for routine prognostic assessment in lymphoma patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty‐five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m2, reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100g/L. Based on the risk model score, the population was divided into the following risk categories: low (score 0‐1), intermediate (score 2‐3), and high (score >3). For patients classified at risk (intermediate and high‐risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high‐risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma – ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014–1019, 2016. © 2016 Wiley Periodicals, Inc.