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 chemotherapy-induced endothelial damage. Correlation with VTE however is difficult as most MM patients on chemotherapy receive thromboprophylaxis as per international guidelines.
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