ALBERT

Description: Introduction: Upper extremity deep vein thrombosis (UEDVT) is a frequent complication of central venous catheters in cancer patients. Anticoagulation with low molecular weight heparin (LMWH) for a minimum of 3 months is the currently recommended treatment for catheter-related UEDVT in cancer patients. Following catheter removal and a minimum of three months of anticoagulant therapy, the risk of recurrence of VTE is likely to be low and it might be reasonable to discontinue anticoagulant therapy. However, there are no data available to support these hypotheses. Therefore, we sought to assess the efficacy and safety of LMWH for the treatment of catheter-related UEDVT in cancer patients and determine the risk of recurrence of VTE after discontinuation of anticoagulation. Material and methods: A retrospective single center cohort study including consecutive cancer outpatients assessed between July 2008 and December 2012 for the management of symptomatic central venous catheter associated proximal UEDVT was conducted. Results: A total of 99 patients were included. Among them, 89 were treated with one month of full therapeutic weight-adjusted dose of LMWH followed by an intermediate dose. A prophylactic dose of LMWH was given after 3 (n=8), 6 (n=4), or 12 (n=1) months of intermediate dosing of LMWH. The remainder patients continued with intermediate dose of LMWH until discontinuation or last follow up. Median duration of anticoagulation was 124 days (range 40 to 1849). No recurrent VTE and two major bleeding episodes occurred during the first 3 months of treatment. Among the 13 patients who were receiving prophylactic doses of LMWH after completion of 3, 6 or 12 months at full and intermediate doses, 2 (15.4%) had a recurrent VTE event. Others did not recurred while on treatment. Eighty-three patients discontinued anticoagulation and 80 could be followed-up after anticoagulation discontinuation for a median of 632 days (range 6 to 2495). Central venous line was pulled out in 77 patients (96.2%). Five recurrences were observed during follow up. The cumulative probability of recurrent VTE was higher in patients whose cancer was active at the time of anticoagulation discontinuation as compared with those in remission (22.2% (95% CI: 0 to 40.6) vs. 2.3% (95% CI: 0 to 6.7)) (Figure 1). Conclusion: LMWH can safely be used to treat catheter associated proximal UEDVT in the setting of cancer. In patients whose central venous line has been pulled and cancer is in remission, anticoagulation therapy can be safely discontinued. Figure 1: cumulative probability of recurrence according to cancer status at the time of anticoagulation discontinuation Disclosures No relevant conflicts of interest to declare.

Description: Introduction Lymphoma patients are at increased risk of thromboembolic events (TE), however, thromboprophylaxis in these patients is largely under utilized. Actual guidelines recommend different models for thromboembolic risk estimation in cancer patients. Proposed models are of limited use in lymphoma patients as their development is not based on specific characteristics for this patient population. Previously, we developed and internally validated a simple model, based on individual clinical and laboratory patient characteristics that would classify lymphoma patients at risk for a TE. The variables independently associated with the 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. For patients classified at risk in derivation cohort (n=1236), the model revealed positive predictive value of 25.1%, negative predictive value of 98.5%, sensitivity of 75.4%, and specificity of 87.5%. The diagnostic performance measures retained similar values in the internal validation cohort (n=584). The aim of this study was to perform external validation of the previously developed thrombosis lymphoma (Throly) score. Methods The study population included patients with a confirmed diagnosis of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) from 8 lymphoma centers from USA, France, Spain, Croatia, Austria, Switzerland, Macedonia, and Jordan. During 2015 to 2016, data were prospectively collected for venous TE events from time of diagnosis to 3 months after the last cycle of therapy for newly diagnosed and relapsed patients who had completed a minimum of one chemotherapy cycle. The score development and validation were done according to TRIPOD suggested guidelines. Sensitivity analyses were carried out to test the model robustness to possible different settings, according to in/out patient settings and according to different countries included. Results External validation cohort included 1723 patients, similar to the developed group and consisted of 467 indolent NHL, 647 aggressive NHL, 235 CLL/SLL and 366 HL patients, out of which 121 (7%) patients developed venous thromboembolic events. For patients classified at risk in external validation cohort, the model resulted in positive and negative predictive values of 17% and 93%, respectively. Based on new available information from this large prospective cohort study this model was revised to include the following variables: diagnosis/clinical stage, previous VTE, reduced mobility, hemoglobin level 〈 100g/L and presence of vascular devices. In the new score we divided patients in two groups: low risk patients, score value ≤ 2; and high risk patients, score value 〉 2. For patients classified at risk by the revised model, the model produced positive predictive value of 22%, negative predictive value of 96%, sensitivity of 51%, and specificity of 72%. In sensitivity analysis, the final model proved its robustness in different settings of major importance for lymphoma patients. The final model presented good discrimination and calibration performance. Concordance C statistics was 0.794 (95% CI 0.750-0.837). Conclusions Revised Thrombosis Lymphoma - ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis risk in solid cancer patients. We included biological characteristic of lymphoma, indolent vs aggressive, as well as data about dissemination of disease, localized vs advanced stage, reflecting specificity of lymphomas comparing to other types of cancer. Also, we pointed out significance of central vascular devices as risk factor having considered the role of vascular damage during insertion as a potential trigger for activation of the clotting cascade. This score is user friendly for daily clinical practice and provides a very good predictive power to identify patients who are candidates for pharmacological thromboprophylaxis. Disclosures Cheson: AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Jaeger:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Takeda-Millenium: Membership on an entity's Board of Directors or advisory committees; Takeda-Millenium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees.

Description: Background: Randomized controlled trials demonstrated that low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux, are efficient for venous thromboembolism (VTE) prevention in acutely ill medical patients. However, asymptomatic VTE, whose clinical relevance is unknown, represented the vast majority of outcome events of these trials. Objectives: Using a case-control design, we aimed to estimate the association between admission to hospital for acute medical illness, prescription of pharmacological thromboprophylaxis during admission and symptomatic VTE. Methods: 750 symptomatic non-surgical, non-cancer, and non-pregnancy-related VTE cases and their 750 age and sex-matched controls were analyzed. Patients hospitalized for an acute medical illness within three months prior to inclusion in the study were identified, and their hospital charts were reviewed. We considered that patients receiving pharmacological thromboprophylaxis were those prescribed either 1) LMWH at an approved preventive dose; 2) low dose UFH (5000 units bid or tid); or 3) fondaparinux 2.5mg once daily, for at least 6 days. Results: Patients' mean age was 67.2 ± 17.1 years, and 664 (44.3%) were men. A total of 145 cases (19.3%) and 91 controls (12.1%) were hospitalized for acute medical illness at least once in the preceding 3 months prior to inclusion in the study (p

Description: Background: Venous thromboembolism (VTE) can be the first manifestation of cancer. Whether screening for an occult malignancy should be systematically performed in patients with unprovoked VTE is a daily challenge for clinicians. Recently, two randomized trials demonstrated that limited cancer screening in patients with a first unprovoked VTE could be the standard of care. However, the one-year incidence of occult malignancy found in these trials was unexpectedly low (4.5%) raising the hypothesis of an inclusion bias. We aimed at estimating the real-life one-year incidence of cancer following a first unprovoked VTE to inform physicians and policy makers in establishing recommendations for cancer screening in VTE patients. Methods: The EPIGETBO study is an epidemiologic study that aimed to measure the incidence of VTE in the Brest District, France1. All symptomatic VTE cases (deep vein thrombosis of the lower limb and pulmonary embolism) diagnosed between March 1st, 2013 and February 28th, 2014 among the 367,911 inhabitants of the district were recorded and validated by an adjudication committee. A systematic follow-up was planned in order to study patients' outcome. Unprovoked VTE was defined as the absence of surgical procedure, pregnancy, delivery, immobilization, admission to hospital for an acute medical illness in the 3 months preceding VTE or known active cancer. The 1-year cumulative incidence of cancer was estimated using the Kaplan-Meier method. Then, the hazard for occult cancer diagnosis associated with age〉60, male sex, and current smoking was assessed by Cox regression. Results: During the study period, 576 symptomatic validated VTE events were diagnosed in 562 inhabitants of the Brest District. Five patients did not undergo follow-up (4 refusals, 1 aged

Description: Abstract 3342 Background: In patients with venous thromboembolism (VTE) provoked by major surgery, the risk of recurrence is low during and after the anticoagulation period. Conversely, cancer patients with VTE have a very high risk of VTE recurrence even under anticoagulant therapy. Some cancer patients develop VTE within three months following surgical treatment of their malignancy. It is unknown whether these patients have a low risk of recurrence of VTE, or if they have the high risk of recurrence associated with cancer. Methods: We analyzed data of a single center cohort study conducted at the Brest University Hospital, France. All consecutive cancer patients with pulmonary embolism and/or deep vein thrombosis of the lower limbs diagnosed between January 2000 and July 2009 in our center were followed-up for VTE recurrence. Patients were classified as “surgical” patients if they had major surgery for cancer in the three months before VTE. Probabilities of recurrence of VTE in surgical patients and in non-surgical patients were estimated according to Kaplan-Meier method and were compared by log-rank test. Hazard Ratios (HR) for VTE recurrence and 95% confidence intervals (CI) were obtained using Cox proportional hazard regression models with adjustments on age, sex, past history of VTE, cancer site, and metastases. Results: We followed 220 cancer patients with symptomatic VTE (mean age 69.9 ± 11.0 years, male sex n=127 (57.7%)). Of these patients, 42 (19.1%) had major surgery for cancer three months before the index VTE and 178 (80.9%) were non-surgical cancer patients. Surgical patients were more often men (30/42 (71.4%) vs. 97/178 (54.5%), p=0.05) and had less metastases at baseline (7/42 (16.7%) vs. 61/178 (34.3%), p=0.03) than non-surgical patients. Mean age was not different between surgical and non-surgical patients (70.1±10.5 vs. 69.8±11.2, p=0.90). Most surgical patients discontinued anticoagulation after six months of treatment, whereas non-surgical patients were receiving long term anticoagulation. At two years, 29 patients had a recurrence of VTE (2/44 surgical patients and 27/180 non-surgical patients). The cumulative probability of recurrence of VTE was lower in surgical patients than in non-surgical patients (2.8% (95% CI −2.5 to 8.1) vs. 11.3% (95% CI 5.8 to 16.8) at 6 months (p=0.14), 3.0% (95% CI −2.3 to 8.3) vs. 16.2% (95% CI 9.3 to 23.1) at 1 year (p=0.06), and 9.3% (95% CI −4.0 to 22.6) vs. 27.5% (95% CI 18. To 36.9) at 2 years (p=0.04)). At two years, the adjusted hazard ratio for recurrence of VTE was 0.20 (95% CI 0.05 to 0.91) in surgical patients compared with non-surgical cancer patients. There was a trend for a lower cumulative probability of death in surgical patients than in non-surgical patients after two years of follow-up (40.2% (95% CI 23.0 to 57.4) vs. 57.7% (95% CI 49.5 to 65.9), p=0.06). Conclusion: In this study, patients with cancer who develop VTE after major cancer surgery had a lower risk of recurrence of VTE than non-surgical cancer patients. Disclosures: No relevant conflicts of interest to declare.