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  • 1
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4945-4945
    Abstract: INTRODUCTION: The prevalence of thrombotic complications in lymphoma patients ranges from 1.5% up to 59.5%. Lymphoma patients have a 10-fold higher risk for the development of venous thrombosis than patients with lung and gastrointestinal cancers. The pathogenesis of thromboembolic disease in hematological malignancies is complex and multifactorial and can be due to the underlying disorder or related to therapy. A number of biomarkers are associated with the occurence of VTE in cancer patients. Biomarkers reflect activation of coagulation and increased inflammatory potential. This study aimed to profile hemostatic and inflammatory biomarkers in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia/ small lymphocytic lymphoma. METHODS: Citrated plasma samples were collected from lymphoma patients (n=96) under an IRB approved protocol Clinic for hematology, Lymphoma Center, University of Belgrade in Serbia. Samples were shipped to Loyola University Chicago and analyzed in batches via commercially available ELISA kits to profile biomarkers of coagulation activation and inflammation. Markers in Coagulation Activation: von Willebrand Factor (vWF), Factor XIIIa, Protein S, β2Glycoprotein I (β2GPI), D-dimer, Microparticles (MP), Urokinase-type Plasminogen Activator Antigen (uPA), Fibronectin. Markers of Inflammation included: Human Tumor Necrosis Factor- α (TNF- α), C-Reactive Protein (CRP), Plasminogen Activator Inhibitor Type 1 (PAI-1). The lymphoma patient population for each biomarker was compared to normal human pooled plasma (repeated 3 times for each biomarker), which consisted of 25 male and 25 females. RESULTS: The mean patients' age was 56 years (range, 19-80 years); 52.4% were males. Most patients were newly diagnosed and had advanced stage disease. A total of 42 patients (43.8%) had high-grade NHL; 17 (17.7%) had low-grade NHL; 24 (25.0%) had HLL; 7(7.3%) had HL; 6 (6.3%) had other forms. Lymphoma patients had significantly dysregulated following markers of coagulation: vWF, β2GPI, D-dimer, MP, uPA, and Fibronectin (Figure 1) (p 〈 0.001 for all in comparison to controls). TNF-α and CRP as markers of inflammation were also significantly increased in lymphoma patients (Figure 1) (p 〈 0.001 for both in comparison to controls). In lymphoma population 12 patients had thrombosis. Patients with thrombosis had significantly higher Factor XIIIa in comparison to lymphoma patients without thrombosis (106±9 vs. 85±256; p 〈 0.001). CONCLUSION: Hemostatic dysregulation and inflammation is present in lymphoma patients, which may reflect increased thrombogenic potential. Further studies are required to link clinical data and biomarker levels, with special emphasis on the involvement of FXIII in the development of thrombotic events in lymphoma patients. Biomarker profiling of lymphoma patients will also help in the understanding of the pathophysiologic mechanisms involved in the observed thrombotic complications and differentiating the sub-groups. Figure 1 Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2772-2775
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3649-3649
    Abstract: 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 & lt;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 & lt;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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2823-2824
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 8-8
    Abstract: INTRODUCTION: Thromboembolism (TE) in lymphoma patients is gathering substantial attention due to its impact on morbidity and mortality of those patients. The association between lymphoma and increased risk for TE development, especially venous thromboembolism (VTE), has lately been well established through numerous publications. Thrombosis Lymphoma (ThroLy) score has been initially developed as a simple risk assessment model for the risk of TE development in lymphoma patients. It has been both internally and externally validated in several studies, which dominantly included patients with non-Hodgkin lymphoma (NHL). Therefore, aim of our study is to analyse and validate ThroLy score in an extensive cohort of Hodgkin lymphoma (HL) patients. METHODS: A total of 5509 newly diagnosed HL patients, from the German Hodgkin Study Group (GHSG) HD13-15 trials, were included in this study. Data has been obtained for all venous and arterial TE events in HL patients from time of diagnosis to 3 months after the last cycle of therapy. TE was diagnosed objectively based on radiographic studies (duplex venous ultrasound, contrast-enhanced thoracic computed tomography scan, magnetic resonance imaging (MRI) - for central nervous system (CNS) thrombosis, or angiograms (for arterial thrombosis), clinical examination and laboratory evaluation. Based on ThroLy score, patients were divided in three risk categories: low (score 0-1), intermediate (score 2-3) and high risk (score & gt;3). Patients with intermediate and high-risk score were classified at risk. The validation was conducted through Chi-square test, ROC analysis and logistic regression. RESULTS: The mean patients' age was 35.9 years (range, 18-75 years); 55.7% were males. The majority of patients had limited or intermediate stage of disease: Ann Arbor stage I 10.6%, and stage II 57.5%. 190 (3.4%) patients developed thromboembolic events, 173 patients with VTE (3.14%), and 17 with arterial TE (0.31%), respectively. Chi-square test showed statistically significant association between TE and ThroLy score, both in three risk groups (chi-square = 18.236, p≤0.001) and two risk groups: low and at risk (chi-square = 18.029, p≤0.001). The sensitivity, specificity, negative and positive predictive value were 49%, 65%, 95%, and 97%, respectively. Binary logistic regression of ThroLy score showed statistically significant performance in prediction of TE events in HL patients, with satisfactory validity indicators (Ombinus Test chi-square = 11.668, p=0.001; AIC=44.956, BIC = 97.869). Diagnostic accuracy of ThroLy score was calculated via ROC curve (area under curve (AUC)=0.57). CONCLUSION: ThroLy score demonstrated its capability of risk prediction for TE events in HL patients. The limited statistical performance of the ThroLy score requires further research towards possible score enhancement. Disclosures Engert: AstraZeneca: Honoraria; MSD Sharp & Dohme: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Affimed Therapeutics: Research Funding; Sandoz: Honoraria; Takeda: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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