Clinical and functional evaluation of new biomarkers for risk stratification in patients with sepsis in hematological malignancies and febrile neutropenia

Abstract

Febrile neutropenia in patients with hematological malignancies is a condition characterized by a high risk of sepsis and septic shock, resulting in the need for aggressive treatment for all patients. However, most patients with febrile neutropenia evolve without complications. Several inflammatory markers and clinical variables have been evaluated as biomarkers for risk stratification of these patients, with promising results in preliminary studies. However, these studies have not yet translated into critical changes in clinical management. In recent years, some authors have explored the role of modulators of vascular permeability in the pathophysiology of sepsis. In line with this approach, our group recently demonstrated that some of these markers, including the angiopoietin 2 and VEGF are associated with a worse prognosis of sepsis in patients with febrile neutropenia. However, these data were obtained in a preliminary study, whose results need to be validated in a study with more patients and that better reproduce real life conditions observed in clinical practice. The aim of this study is to evaluate levels of VEGF-A, sFlt-1, Ang1 and Ang2 as prognostic factors in sepsis. The results will be compared with classical markers of prognosis in sepsis such as C-reactive protein and the MASCC score, and evaluated with regard to its accuracy by specific statistical methodology. The primary clinical endpoint in our study will be progression to septic shock during neutropenia. The study design anticipates the recruitment from 120 to 200 patients. Furthermore, we will evaluate the effect of plasma of these patients in an in vitro model for assessment of vascular permeability using endothelial cell cultures. The results of these assays will be analyzed in conjunction with levels of the 4 biomarkers tested, to verify the biological relevance of any statistical association. Moreover, these permeability tests will serve as a platform for studies of inhibition and stimulation of specific elements of the cascade of events that modulates vascular permeability in sepsis, with focus on VEGF-A, sFlt-1, Ang1 and Ang2, whose role in this cascade needs to be further clarified. (AU)