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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
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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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 3
    In: Journal of Hematology & Oncology, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2022-08-26)
    Abstract: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
    Type of Medium: Online Resource
    ISSN: 1756-8722
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2429631-4
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  • 4
    In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e1785725-
    Type of Medium: Online Resource
    ISSN: 2572-9241
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2922183-3
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  • 5
    Online Resource
    Online Resource
    National Library of Serbia ; 2022
    In:  Medical review Vol. 75, No. Suppl. 1 ( 2022), p. 106-110
    In: Medical review, National Library of Serbia, Vol. 75, No. Suppl. 1 ( 2022), p. 106-110
    Abstract: Diffuse large B-cell lymphoma, not otherwise specified, is the most common type of non-Hodgkin lymphoma worldwide, accounting for 30-40% of all lymphomas. It represents a collection of morphologically, genetically and clinically different diseases. Therefore, it can be subdivided into morphological variants, phenotypic subtypes, and molecular or genetic categories. More recently, diffuse large B-cell lymphoma has witnessed advances in molecular profiling and treatment of patients with refractory and relapsed disease. The optimal management requires integrated morphological and immunophenotypic analysis of cell and tissue, along with chromosome and molecular analyses. Double-expressor lymphoma, defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, accounts for 20% to 30% of Diffuse large B-cell lymphoma cases. In the latest, 5th edition of the World Health Organization Classification of Hematolymphoid Tumors-lymphoid neoplasms, double-expressor lymphoma is not defined as an independent entity, but it has been proven to be a marker for poor outcome in diffuse large B-cell lymphoma. However, the degree of adverse prognosis is lesser than in double-hit lymphomas. Although double-expressor lymphoma feature is confirmed as adverse prognostic marker for diffuse large B-cell lymphoma patients, currently no sufficient data is available to support treatment intensification over standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone regimen. Well-designed randomized clinical trials are mandatory in order to properly respond to this substantial clinical dispute.
    Type of Medium: Online Resource
    ISSN: 0025-8105 , 1820-7383
    Language: English
    Publisher: National Library of Serbia
    Publication Date: 2022
    detail.hit.zdb_id: 2381028-2
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  • 6
    In: Medical review, National Library of Serbia, Vol. 75, No. Suppl. 1 ( 2022), p. 111-114
    Abstract: Nodular lymphocyte predominant Hodgkin lymphoma appears in 5% of Hodgkin lymphoma. Because of major biological and clinical differences with classical Hodgkin lymphoma and close relationship to T-cell/histiocyte-rich large B-cell lymphoma, lately the term nodular lymphocyte predominant B-cell lymphoma is accepted. The presence of lymphocyte predominant cells with preserved B-cell phenotype and a lack of CD30 is the prerequisite for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. Lymphocyte predominant cells are typically embedded in large nodules of B lymphocytes (growth patterns A and B), but variants that are characterized by lymphocyte predominant cells located outside the nodules, a Tcell- rich nodular growth pattern and T-cell-rich or B-cell-rich diffuse growth patterns, respectively, have also been described (growth patterns C, D, E, and F). Variant growth patterns are associated with the recurrence and progression of disease and should be recognized and specified in pathology reports. Broad B-cell immunohistochemical panel, including PAX5, CD79a, Bob.1, and Oct-2 is indicated in these cases to distinguish between nodular lymphocyte predominant Hodgkin lymphoma, classical Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma, which have significant differences in clinical behavior and treatment. There are different treatment approaches in patients with nodular lymphocyte predominant Hodgkin lymphoma depending on pathohistological type, clinical presentation and stage of the disease. Treatment may include active surveillance, radiation therapy, immunotherapy or chemotherapy. A multidisciplinary approach is beneficial to optimize the diagnosis and management of patients with nodular lymphocyte predominant Hodgkin lymphoma.
    Type of Medium: Online Resource
    ISSN: 0025-8105 , 1820-7383
    Language: English
    Publisher: National Library of Serbia
    Publication Date: 2022
    detail.hit.zdb_id: 2381028-2
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  • 7
    In: International Journal of Laboratory Hematology, Wiley, Vol. 45, No. 1 ( 2023-02), p. 64-71
    Abstract: The B‐cell lymphoma/leukaemia 11A ( BCL11A ) gene encodes a Krüppel‐like transcription factor involved in lymphocyte development during normal haematopoiesis. Aberrant expression of BCL11A has been observed in several haematological malignancies, including chronic lymphocytic leukaemia (CLL). However, its functions in the regulatory networks of malignant B lymphocytes are poorly understood, as are the relations to clinical course and outcome of B‐cell malignancies, particularly CLL. Methods The expression of BCL11A was analysed in peripheral blood mononuclear cells of 87 newly‐diagnosed CLL patients by quantitative reverse‐transcriptase polymerase chain reaction (qRT‐PCR), and association with clinical and molecular variables was assessed. Results BCL11A was significantly overexpressed in CLL samples compared to control samples ( p   〈  0.001). BCL11A expression level exhibited no association with age, sex, leukocyte, lymphocyte and platelet counts, haemoglobin level, serum β2‐microglobulin, CD38 status and cytogenetic abnormalities. On the other hand, high BCL11A expression was associated with low serum lactate dehydrogenase ( p  = 0.031), Binet A stage ( p  = 0.047) and mutated IGHV ( p  = 0.028). In addition, a positive correlation with BCL2/BAX mRNA ratio was observed (r = 0.36; p   〈  0.001). Regarding the association with the time to first treatment (TTFT), a trend towards longer median TTFT in BCL11A high‐ versus BCL11A low‐expressing cases was detected (21 vs. 6 months; p  = 0.164). Conclusion The results of this study show that BCL11A is upregulated in CLL patients, and that high BCL11A expression at diagnosis may be associated with better prognosis. These data are consistent with the role of BCL11A expression in CLL biology, and imply its potential prognostic relevance.
    Type of Medium: Online Resource
    ISSN: 1751-5521 , 1751-553X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2268600-9
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  • 8
    In: Thrombosis Journal, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: Lymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma. Methods The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE. Results The majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE. Conclusion Inflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.
    Type of Medium: Online Resource
    ISSN: 1477-9560
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 9
    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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
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  • 10
    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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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