Κλινική συσχέτιση των επιπέδων των αγγειογενετικών παραγόντων VEGF και HGF με τα επίπεδα της NT-pro BNP και τροπονίνης- T σε σχέση με το ποσό των ελ...

Abstract

Primary systemic light chain (AL) amyloidosis is characterized by the deposition of immunoglobulin light chain-derived amyloid fibrils in various tissues leading to multiorgan dysfunction. In order to define characteristics, treatment and outcome of Greek AL patients we analyzed 112 unselected AL patients from several hospitals. Induction of angiogenesis is a significant step for the progression and evolution of plasma cell dyscrasias, such as myeloma (MM). Several growth factors regulate angiogenesis but there are no data about their role and possible correlations with disease features or outcome in patients with AL amyloidosis. We measured the serum levels of VEGF, Ang-1, Ang-2, angiogenin and bFGF in 82 patients with AL amyloidosis and compared to their respective serum levels in normal individuals and MM patients. Results: Heart was involved in 59% and kidneys in 71%. Patients were treated with several different treatment regimens; high-dose dexamethasone based regimens were used as primary treatment in 43% and melphalan-based regimens in 37% while 12% received upfront bortezomib with dexamethasone. A hematologic response to first line therapy was documented in 50% (14.5% CR), and organ responses were seen in 25% of patients; the latter being strongly associated with achievement of hematologic response. Median overall survival was 34.2 months and was independently affected by heart involvement, creatinine, age, involvement of 2 or more organs and bone marrow plasmacytosis>30%. In patients with cardiac involvement, advanced age and extended bone marrow plasmacytosis were associated with an even worse outcome while for patients without heart involvement only bone marrow plasmacytosis was independently associated with survival. Hematologic response was associated with improved survival in patient with heart involvement but mostly in patients with less bone marrow infiltration. Serum levels of VEGF (p<0.001), bFGF (<0.001) and angiogenin (p<0.001) were higher in patients with AL amyloidosis compared to normal controls. Both Ang-1 (p<0.001) and Ang-2 (p<0.001) were also higher but their respective Ang-1/Ang-2 ratio was lower in AL patients than in healthy controls (p=0.036). VEGF was twice as high in patients with AL compared to MM patients (p<0.001); angiogenin (p<0.001) and Ang-1 (p=0.001) were also higher, but Ang-2 was higher in myeloma patients (p=0.086) thus, the resulting Ang-1/Ang-2 ratio was higher in AL than in MM patients (p<0.001). Serum levels of ang-2 were correlated with cardiac involvement (p=0.001), NYHA class and NT-proBNP. The serum levels of angiogenic growth factors were not predictive for disease outcome. Conclusion: In this first series of AL amyloidosis patients from Greece, disease features and outcome appeared similar to those reported from tertiary centers. Heart involvement and bone marrow plasma cell infiltration comprise adverse prognostic factors but also indicate the heterogeneity of the disease and the need for individual treatment approaches. The serum levels of angiogenic cytokines are significantly elevated in patients with AL amyloidosis, but have a pattern different than in myeloma patients, perhaps as a result of direct or indirect activity of amyloid fibrils or light chains or compensatory to organ dysfunction.