- Email: [email protected]
PO-28 - Protein C levels are associated with mortality in patients with advanced cancer
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Abstracts / Thrombosis Research 140S1 (2016) S168–S200
Aim: This study assess the feasibility of using ROTEM to characterize the prothrombotic state of MPN patients and to evaluate whether the thromboelastometry profile varies according to mutational status and/or treatment, and is influenced by hemocromocytometric parameters. Materials and Methods: Venous blood samples were collected from 39 ET and 23 PV patients upon informed consent. Analysis was performed using INTEM and EXTEM reagents, to evaluate the intrinsic and extrinsic pathway, respectively. Maximum clot firmness (MCF, [mm]), which reflects the maximum tensile strength of the thrombus, clotting formation time (CFT [sec]), namely the time that clot takes to increase from 2 to 20 mm above baseline, and clotting time (CT [sec]), the time to clot initiation, were recorded. Nineteen healthy subjects acted as a control group. Results: ROTEM analysis showed a hypercoagulable profile in MPN patients, who had shorter CFT and higher MCF compared to controls, both with EXTEM and INTEM reagents; no differences were observed in CT parameters. Platelet count was significantly higher in patients compared to controls (p<0.01). In patients, a strong statistically significant (p<0.01) correlation was found between platelet count, and MCF [r=0.650 (ET), r=0.601 (PV)] or CFT [r=-0.641 (ET), r=-0.558 (PV)]. Multivariate analysis, according to blood cell counts, showed that only platelet count was independently associated to ROTEM results. To correct for platelet differences, a ratio between MCF and the respective platelet value (rMCF) was created. Interestingly, rMCF was significantly lower in patients compared to controls (p<0.01), suggesting a weaker clot formation potential of patients’ samples. Furthermore, rMCF was lower in ET compared to PV (p<0.05), and in calreticulin-positive subjects (p<0.05), while was higher in patients under cytoreductive therapy (Hydroxyurea) (p=ns). Conclusions: This study confirms, by the ROTEM evaluation, the occurrence of a hypercoagulable state in ET and PV patients. In addition, the ROTEM parameters are significantly influenced by the platelet count. Finally, MCF values corrected for platelet count reveal a lower platelet reactivity in MPN patients, confirming the hypothesis that platelet function is exhausted upon clotting activation. Acknowledgement: Project funded by “AIRC-IG2013” grant Nr. 14505 from the “Italian Association for Cancer Research” (A.I.R.C.).
PO-27 Thrombin generation in pancreatic cancer and multiple myeloma with use of calibrated automated thrombography M.A. Adesanya1, A. Maraveyas1, L.A. Madden2 Hull York Medical School, Universities of Hull and York, USA, 2School of Biological, Biomedical and Environmental Sciences, University of Hull, UK 1
Introduction: The calibrated automated thrombography (CAT) assay is emerging as a reliable tool for real time estimation of thrombin generation (TG) potential. As a time-dependent colorimetric assessment of thrombin quantity generated per sample, it measures the amount of thrombincleaved fluorogenic substrate produced, and so is regarded as a better overall indicator of the clotting efficiency and function of the haemostatic process than one stage clotting-time based assays. Aim: We already recognise that the pathways underlying the thrombotic phenotype for different malignancies may be driven by different factors of the coagulation cascade with TG has a common denominator. Two such malignancies with high venous thromboembolism (VTE) incidence are Multiple myeloma (MM) and Pancreatic cancer (PC). Understanding the underlying variations in these two distinct cancer models using patient samples and cell lines might potentially allow individual approaches to identifying thrombotic risk and relevant prevention strategies. Materials and Methods: Citrated blood samples were taken from healthy controls, pre-surgical pancreatic cancer and pre-chemotherapy multiple myeloma patients enrolled into ongoing clinical trials. The clotting ability was tested using platelet free plasma (PPP) on a one-step clotting timebased (CT) assay and the TG profiles were evaluated on a Thrombinoscope™ software (Thrombinoscope BV, Maastricht, Netherlands). Solid tumour cells of pancreatic cancer and malignant haematological cell lines were used at various cell concentrations for the CAT assay, which was performed with
the addition of platelet-free control plasma or control plasma deficient in coagulation factors VII and XII. Results: At TF concentration conditions of 1 pmol/L, the peak height of thrombin generated on thrombogram curves strongly correlated with CT of patient samples. Compared to healthy controls, pancreatic cancer had higher thrombin peaks (P), shorter lag times (LG), and an overall stronger TG profile than MM. Pancreatic cancer cell lines exhibited higher concentrationdependent TG profiles in control plasma than haematological cell lines, with higher peaks, endogenous thrombin potential (ETP), shorter lag times (LG) and faster times-to-peak (ttPeak). Conclusions: This study demonstrates that the CAT assay is a useful predictor of the thrombotic phenotype in cancer patients as it gives a more comprehensive overall coagulation profile than one stage CT-based assays. It shows that for patient samples and cell lines, the similarities and differences that exists in the TG potential, significantly depends on specific coagulation factors present in the intrinsic or extrinsic arms of the clotting cascade.
PO-28 Protein C levels are associated with mortality in patients with advanced cancer I.T. Wilts1, B.A. Hutten2, J.C. Meijers3,4, C.A. Spek5, H.R. Büller3, P.W. Kamphuisen1 1 Dept. of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 2Dept. of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Medical Center, 3Dept. of Vascular Medicine, Amsterdam Medical Center, 4Dept. of Plasma Proteins, Sanquin Blood Supply, 5Center for Experimental and Molecular Medicine, Amsterdam Medical Center, Amsterdam, The Netherlands Introduction: In cancer, tumor progression and metastasis are promoted by prohemostatic activity. Protein C (PC) is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated PC reduced experimental metastasis. It is unclear whether PC level is associated with mortality in patients with cancer. Aim: To assess the relation between PC level and survival in patients with advanced cancer. Materials and Methods: A multicenter, randomized, open-label study was performed in 11 countries between May 2006 and August 2008 (INPACT study, van Doormaal et al, JCO 2011). Patients (n=503) with hormonerefractory prostate cancer, non-small cell lung cancer stage IIIB and locally advanced pancreatic cancer were randomized to receive nadroparin or placebo for 6 to 46 weeks following a specific schedule. Patients were followed till death or the end of the study in May 2009. PC activity levels were measured at baseline and categorized in tertiles. The association between PC level and mortality was evaluated with Cox proportional hazard models, adjustments were made by multivariate Cox proportional hazard models. Results: PC activity could be measured in 479 (95%) patients (tertiles: <97, 97-120 and >120%). Two patients with missing information on type of cancer were excluded. Mean age was 65±10 years; 87 (18%) were female; and 161 patients had lung cancer, 125 pancreatic cancer and 191 prostate cancer. During median follow-up of 10.5 months, 291 (61%) patients died. Median PC activity was 107% (IQR 92-129). There was a clear inverse relation between PC activity and mortality (p for trend=0.036). In the lowest tertile, mortality was 66%, in the middle and high tertile 61% and 56%, respectively. Compared to the highest tertile, the lowest tertile was associated with a HR on mortality of 1.36 (95% CI 1.02-1.80). Adjustment for age, gender and nadroparin use did not affect this association. The association appeared to be strongest in the patients with lung cancer, HR 0.818 (p=0.11) as compared to the patients with prostate cancer, HR 0.972 (p=0.83) and pancreatic cancer, HR 0.950 (p=0.68). Conclusions: Lower PC activity is associated with increased mortality in patients with advanced cancer. However, validation of our findings in a larger cohort is necessary. When the association of PC and mortality has
Abstracts / Thrombosis Research 140S1 (2016) S168–S200
been proven to be consistent, we would suggest a trial on suppletion of PC in cancer patients.
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immobilisation. The prevalence of PE was 108/429 (25.2%) in cancer patients and 522/2894 (18%) in patients without cancer, p<0.001. Among cancer patients with an unlikely CDR, 27/274 (9.9%) had a D-Dimer <500 g/L as compared with 19.7% using the age-adjusted D-dimer cut-off; in patients without cancer, these rates were 30.1% and 41.9%, respectively. The percentage of cancer patients in whom PE could be excluded based on CDR and age-adjusted D-dimer doubled from 6.3% to 12.6%. None of these cancer patients had a venous thromboembolic event during three-month followup, thus the failure rate was 0.0% (95% CI 0.0-6.9%). Conclusions: Compared with the usual cut-off, the age-adjusted D-dimer cut-off doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and D-dimer without need for CTPA imaging.
PO-30 Changes in soluble CD106 and CD54 serum levels during chemotherapy treatment for multiple myeloma J. Hall1, M.A. Adesanya1, L.A Madden2, A. Maraveyas1 Hull York Medical School, Universities of Hull and York, 2School of Biological, Biomedical and Environmental Sciences, University of Hull, United Kingdom
1
Fig. 1.
PO-29 Age-adjusted D-dimer cutoff level increases the number of cancer patients in who pulmonary embolism can be safely excluded without CT-PA imaging: The ADJUST-PE cancer substudy I.T. Wilts1, G. Le Gal2, P.L. den Exter3, J. van Es4, M. Carrier2, B. Planquette5, H.R. Büller4, M. Righini6, M.V. Huisman3, P.W. Kamphuisen1 1 Dept. of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands, 2Health Research Institute, Ottawa, Canada, 3 Dept. of Thrombosis and Hemostasis, Leiden University Medical Center, The Netherlands, 4Dept. of Vascular Medicine, Amsterdam Medical Center, the Netherlands, 5Service de pneumologie et de soins intensifs, Hôpital Européen Georges Pompidou, Paris, France, 6Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Switzerland Introduction: Patients with cancer frequently present with suspected pulmonary embolism (PE). The D-dimer test is less useful to rule out PE in cancer patients due to a lower specificity, whereas the safety of the combination of a clinical decision rule (CDR) and D-dimer test to rule out PE in these patients is unclear. In the general population, use of an ageadjusted cutoff for D-dimer in combination with a CDR has been shown to improve specificity in the diagnosis of PE. Aim: We prospectively analysed the safety and efficacy of the age-adjusted D-dimer (defined as age × 10 in patients >50 years) combined with CDR for the exclusion of PE in patients with cancer. Materials and Methods: We conducted a multicenter multinational prospective management outcome study in 19 centers in Belgium, France, The Netherlands and Switzerland, the ADJUST-PE study, to validate an ageadjusted D-dimer cut-off in patients with suspected PE. The performance of the age-adjusted D-dimer cut-off and CDR was compared between patients with and without cancer. The primary outcome was the rate of adjudicated thromboembolic events during three-month follow-up. Results: Of the 3,324 patients with suspected PE, 429 (12.9%) patients had cancer. Cancer patients were older and more often had surgery or
Introduction: IMiD-based regimens are now widely considered standard of care in the treatment of Multiple myeloma (MM) patients (Kumar et al., 2008). One of the major adverse events noted in many MM clinical studies in patients treated with combination regimens including Thalidomide (Thal), Lenanlidomide (Len) and dexamethasone or chemotherapy was the development of hrombosis (Carrier et al., 2011). Aim: We have postulated that one mechanism for venous thromboembolism (VTE) occurrence may be through chemotherapy damage to endothelium (Date et al., 2013) and much recent work has centred on the study of soluble dysfunction markers to predict this event. In states of endothelial dysfunction soluble antigen concentrations of circulating endothelial activation markers sCD106 and sCD54 have been shown to increase (Burger and Touyz, 2012), and sCD106 was recently associated with inferior survival in newly diagnosed MM patients treated with Thal- or Len-based therapies (Terpos et al., 2013). Materials and Methods: Serum from newly diagnosed and relapsed MM patients were collected before, during and after prescribed chemotherapy courses (minimum of 4 cycles). Levels of endothelial activation markers sCD106 and sCD54 were evaluated by quantitative ELISA (Platinum ELISA kits; eBioscience, Hatfield, UK). Results: The percentage mean ± SD change in the serum concentration of sCD106 increased by 25.8% after the first cycle of chemotherapy (T2; n=10) relative to T1 prior to chemotherapy administration. These levels subsequently decreased after the second cycle of chemotherapy (T3; n=9) and after completion (T4; n=5), but were still higher than baseline levels (15.5 and 15.3% increase in comparison to baseline, respectively). In contrast, the mean±SD percentage change in sCD54 relative to T1 were similar after the first cycle (T2; n=10) and the second cycle (T3; n=9), but increased by 15.0% after completion of chemotherapy (T4; n=5). Additionally, a statistical correlation was found to exist between the serum concentration of sCD106 and sCD54 (Pearson’s correlation coefficient r=0.84, p <0.0005) for all analysed samples (n=39). Conclusions: In this study, the increase in serum levels of both sCD106 and sCD54 after IMiD-based chemotherapy implies a disruptive effect of these combination regimens on the vascular endothelium. This agrees with previous studies where serum levels of sCD106 were shown to be significantly elevated in chronic lymphocytic leukaemia patients on Len indicating Len-induced endothelial dysfunction, and associated with subsequent DVT development (Aue et al., 2011). Our study confirms the potential significance of these biomarkers in demonstrating chemotherapyinduced endothelial damage. Correlation with VTE however is difficult as most MM patients on chemotherapy receive thromboprophylaxis as per international guidelines.
Abstracts / Thrombosis Research 140S1 (2016) S168–S200
Aim: This study assess the feasibility of using ROTEM to characterize the prothrombotic state of MPN patients and to evaluate whether the thromboelastometry profile varies according to mutational status and/or treatment, and is influenced by hemocromocytometric parameters. Materials and Methods: Venous blood samples were collected from 39 ET and 23 PV patients upon informed consent. Analysis was performed using INTEM and EXTEM reagents, to evaluate the intrinsic and extrinsic pathway, respectively. Maximum clot firmness (MCF, [mm]), which reflects the maximum tensile strength of the thrombus, clotting formation time (CFT [sec]), namely the time that clot takes to increase from 2 to 20 mm above baseline, and clotting time (CT [sec]), the time to clot initiation, were recorded. Nineteen healthy subjects acted as a control group. Results: ROTEM analysis showed a hypercoagulable profile in MPN patients, who had shorter CFT and higher MCF compared to controls, both with EXTEM and INTEM reagents; no differences were observed in CT parameters. Platelet count was significantly higher in patients compared to controls (p<0.01). In patients, a strong statistically significant (p<0.01) correlation was found between platelet count, and MCF [r=0.650 (ET), r=0.601 (PV)] or CFT [r=-0.641 (ET), r=-0.558 (PV)]. Multivariate analysis, according to blood cell counts, showed that only platelet count was independently associated to ROTEM results. To correct for platelet differences, a ratio between MCF and the respective platelet value (rMCF) was created. Interestingly, rMCF was significantly lower in patients compared to controls (p<0.01), suggesting a weaker clot formation potential of patients’ samples. Furthermore, rMCF was lower in ET compared to PV (p<0.05), and in calreticulin-positive subjects (p<0.05), while was higher in patients under cytoreductive therapy (Hydroxyurea) (p=ns). Conclusions: This study confirms, by the ROTEM evaluation, the occurrence of a hypercoagulable state in ET and PV patients. In addition, the ROTEM parameters are significantly influenced by the platelet count. Finally, MCF values corrected for platelet count reveal a lower platelet reactivity in MPN patients, confirming the hypothesis that platelet function is exhausted upon clotting activation. Acknowledgement: Project funded by “AIRC-IG2013” grant Nr. 14505 from the “Italian Association for Cancer Research” (A.I.R.C.).
PO-27 Thrombin generation in pancreatic cancer and multiple myeloma with use of calibrated automated thrombography M.A. Adesanya1, A. Maraveyas1, L.A. Madden2 Hull York Medical School, Universities of Hull and York, USA, 2School of Biological, Biomedical and Environmental Sciences, University of Hull, UK 1
Introduction: The calibrated automated thrombography (CAT) assay is emerging as a reliable tool for real time estimation of thrombin generation (TG) potential. As a time-dependent colorimetric assessment of thrombin quantity generated per sample, it measures the amount of thrombincleaved fluorogenic substrate produced, and so is regarded as a better overall indicator of the clotting efficiency and function of the haemostatic process than one stage clotting-time based assays. Aim: We already recognise that the pathways underlying the thrombotic phenotype for different malignancies may be driven by different factors of the coagulation cascade with TG has a common denominator. Two such malignancies with high venous thromboembolism (VTE) incidence are Multiple myeloma (MM) and Pancreatic cancer (PC). Understanding the underlying variations in these two distinct cancer models using patient samples and cell lines might potentially allow individual approaches to identifying thrombotic risk and relevant prevention strategies. Materials and Methods: Citrated blood samples were taken from healthy controls, pre-surgical pancreatic cancer and pre-chemotherapy multiple myeloma patients enrolled into ongoing clinical trials. The clotting ability was tested using platelet free plasma (PPP) on a one-step clotting timebased (CT) assay and the TG profiles were evaluated on a Thrombinoscope™ software (Thrombinoscope BV, Maastricht, Netherlands). Solid tumour cells of pancreatic cancer and malignant haematological cell lines were used at various cell concentrations for the CAT assay, which was performed with
the addition of platelet-free control plasma or control plasma deficient in coagulation factors VII and XII. Results: At TF concentration conditions of 1 pmol/L, the peak height of thrombin generated on thrombogram curves strongly correlated with CT of patient samples. Compared to healthy controls, pancreatic cancer had higher thrombin peaks (P), shorter lag times (LG), and an overall stronger TG profile than MM. Pancreatic cancer cell lines exhibited higher concentrationdependent TG profiles in control plasma than haematological cell lines, with higher peaks, endogenous thrombin potential (ETP), shorter lag times (LG) and faster times-to-peak (ttPeak). Conclusions: This study demonstrates that the CAT assay is a useful predictor of the thrombotic phenotype in cancer patients as it gives a more comprehensive overall coagulation profile than one stage CT-based assays. It shows that for patient samples and cell lines, the similarities and differences that exists in the TG potential, significantly depends on specific coagulation factors present in the intrinsic or extrinsic arms of the clotting cascade.
PO-28 Protein C levels are associated with mortality in patients with advanced cancer I.T. Wilts1, B.A. Hutten2, J.C. Meijers3,4, C.A. Spek5, H.R. Büller3, P.W. Kamphuisen1 1 Dept. of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 2Dept. of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Medical Center, 3Dept. of Vascular Medicine, Amsterdam Medical Center, 4Dept. of Plasma Proteins, Sanquin Blood Supply, 5Center for Experimental and Molecular Medicine, Amsterdam Medical Center, Amsterdam, The Netherlands Introduction: In cancer, tumor progression and metastasis are promoted by prohemostatic activity. Protein C (PC) is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated PC reduced experimental metastasis. It is unclear whether PC level is associated with mortality in patients with cancer. Aim: To assess the relation between PC level and survival in patients with advanced cancer. Materials and Methods: A multicenter, randomized, open-label study was performed in 11 countries between May 2006 and August 2008 (INPACT study, van Doormaal et al, JCO 2011). Patients (n=503) with hormonerefractory prostate cancer, non-small cell lung cancer stage IIIB and locally advanced pancreatic cancer were randomized to receive nadroparin or placebo for 6 to 46 weeks following a specific schedule. Patients were followed till death or the end of the study in May 2009. PC activity levels were measured at baseline and categorized in tertiles. The association between PC level and mortality was evaluated with Cox proportional hazard models, adjustments were made by multivariate Cox proportional hazard models. Results: PC activity could be measured in 479 (95%) patients (tertiles: <97, 97-120 and >120%). Two patients with missing information on type of cancer were excluded. Mean age was 65±10 years; 87 (18%) were female; and 161 patients had lung cancer, 125 pancreatic cancer and 191 prostate cancer. During median follow-up of 10.5 months, 291 (61%) patients died. Median PC activity was 107% (IQR 92-129). There was a clear inverse relation between PC activity and mortality (p for trend=0.036). In the lowest tertile, mortality was 66%, in the middle and high tertile 61% and 56%, respectively. Compared to the highest tertile, the lowest tertile was associated with a HR on mortality of 1.36 (95% CI 1.02-1.80). Adjustment for age, gender and nadroparin use did not affect this association. The association appeared to be strongest in the patients with lung cancer, HR 0.818 (p=0.11) as compared to the patients with prostate cancer, HR 0.972 (p=0.83) and pancreatic cancer, HR 0.950 (p=0.68). Conclusions: Lower PC activity is associated with increased mortality in patients with advanced cancer. However, validation of our findings in a larger cohort is necessary. When the association of PC and mortality has
Abstracts / Thrombosis Research 140S1 (2016) S168–S200
been proven to be consistent, we would suggest a trial on suppletion of PC in cancer patients.
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immobilisation. The prevalence of PE was 108/429 (25.2%) in cancer patients and 522/2894 (18%) in patients without cancer, p<0.001. Among cancer patients with an unlikely CDR, 27/274 (9.9%) had a D-Dimer <500 g/L as compared with 19.7% using the age-adjusted D-dimer cut-off; in patients without cancer, these rates were 30.1% and 41.9%, respectively. The percentage of cancer patients in whom PE could be excluded based on CDR and age-adjusted D-dimer doubled from 6.3% to 12.6%. None of these cancer patients had a venous thromboembolic event during three-month followup, thus the failure rate was 0.0% (95% CI 0.0-6.9%). Conclusions: Compared with the usual cut-off, the age-adjusted D-dimer cut-off doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and D-dimer without need for CTPA imaging.
PO-30 Changes in soluble CD106 and CD54 serum levels during chemotherapy treatment for multiple myeloma J. Hall1, M.A. Adesanya1, L.A Madden2, A. Maraveyas1 Hull York Medical School, Universities of Hull and York, 2School of Biological, Biomedical and Environmental Sciences, University of Hull, United Kingdom
1
Fig. 1.
PO-29 Age-adjusted D-dimer cutoff level increases the number of cancer patients in who pulmonary embolism can be safely excluded without CT-PA imaging: The ADJUST-PE cancer substudy I.T. Wilts1, G. Le Gal2, P.L. den Exter3, J. van Es4, M. Carrier2, B. Planquette5, H.R. Büller4, M. Righini6, M.V. Huisman3, P.W. Kamphuisen1 1 Dept. of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands, 2Health Research Institute, Ottawa, Canada, 3 Dept. of Thrombosis and Hemostasis, Leiden University Medical Center, The Netherlands, 4Dept. of Vascular Medicine, Amsterdam Medical Center, the Netherlands, 5Service de pneumologie et de soins intensifs, Hôpital Européen Georges Pompidou, Paris, France, 6Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Switzerland Introduction: Patients with cancer frequently present with suspected pulmonary embolism (PE). The D-dimer test is less useful to rule out PE in cancer patients due to a lower specificity, whereas the safety of the combination of a clinical decision rule (CDR) and D-dimer test to rule out PE in these patients is unclear. In the general population, use of an ageadjusted cutoff for D-dimer in combination with a CDR has been shown to improve specificity in the diagnosis of PE. Aim: We prospectively analysed the safety and efficacy of the age-adjusted D-dimer (defined as age × 10 in patients >50 years) combined with CDR for the exclusion of PE in patients with cancer. Materials and Methods: We conducted a multicenter multinational prospective management outcome study in 19 centers in Belgium, France, The Netherlands and Switzerland, the ADJUST-PE study, to validate an ageadjusted D-dimer cut-off in patients with suspected PE. The performance of the age-adjusted D-dimer cut-off and CDR was compared between patients with and without cancer. The primary outcome was the rate of adjudicated thromboembolic events during three-month follow-up. Results: Of the 3,324 patients with suspected PE, 429 (12.9%) patients had cancer. Cancer patients were older and more often had surgery or
Introduction: IMiD-based regimens are now widely considered standard of care in the treatment of Multiple myeloma (MM) patients (Kumar et al., 2008). One of the major adverse events noted in many MM clinical studies in patients treated with combination regimens including Thalidomide (Thal), Lenanlidomide (Len) and dexamethasone or chemotherapy was the development of hrombosis (Carrier et al., 2011). Aim: We have postulated that one mechanism for venous thromboembolism (VTE) occurrence may be through chemotherapy damage to endothelium (Date et al., 2013) and much recent work has centred on the study of soluble dysfunction markers to predict this event. In states of endothelial dysfunction soluble antigen concentrations of circulating endothelial activation markers sCD106 and sCD54 have been shown to increase (Burger and Touyz, 2012), and sCD106 was recently associated with inferior survival in newly diagnosed MM patients treated with Thal- or Len-based therapies (Terpos et al., 2013). Materials and Methods: Serum from newly diagnosed and relapsed MM patients were collected before, during and after prescribed chemotherapy courses (minimum of 4 cycles). Levels of endothelial activation markers sCD106 and sCD54 were evaluated by quantitative ELISA (Platinum ELISA kits; eBioscience, Hatfield, UK). Results: The percentage mean ± SD change in the serum concentration of sCD106 increased by 25.8% after the first cycle of chemotherapy (T2; n=10) relative to T1 prior to chemotherapy administration. These levels subsequently decreased after the second cycle of chemotherapy (T3; n=9) and after completion (T4; n=5), but were still higher than baseline levels (15.5 and 15.3% increase in comparison to baseline, respectively). In contrast, the mean±SD percentage change in sCD54 relative to T1 were similar after the first cycle (T2; n=10) and the second cycle (T3; n=9), but increased by 15.0% after completion of chemotherapy (T4; n=5). Additionally, a statistical correlation was found to exist between the serum concentration of sCD106 and sCD54 (Pearson’s correlation coefficient r=0.84, p <0.0005) for all analysed samples (n=39). Conclusions: In this study, the increase in serum levels of both sCD106 and sCD54 after IMiD-based chemotherapy implies a disruptive effect of these combination regimens on the vascular endothelium. This agrees with previous studies where serum levels of sCD106 were shown to be significantly elevated in chronic lymphocytic leukaemia patients on Len indicating Len-induced endothelial dysfunction, and associated with subsequent DVT development (Aue et al., 2011). Our study confirms the potential significance of these biomarkers in demonstrating chemotherapyinduced endothelial damage. Correlation with VTE however is difficult as most MM patients on chemotherapy receive thromboprophylaxis as per international guidelines.