The Endothelial Cell Dysfunction and Outcome Project for Hematological Neoplasms

The endothelium is a semipermeable monolayer of endothelial cells (EC) organized as a complex biological interface that separates all tissues from circulating blood. Any anti-neoplastic or immune therapy will directly challenge the endothelial layer, with a substantial risk of damaging EC or exacerbating pre-existing endothelial cell dysfunction. In our previous researchs the concepts of "endothelial vulnerability" and "endothelial cell dysfunction" for initial diagnosis of patients with hematological disorders, e.g. myelodysplastic syndromes as well as COVID-19 patients were designed. The novel and pre-existing endothelial vulnerability markers and markers of endothelial cell dysfunction or damage such as endothelial activation and stress index (EASIX) were also defined, validated and their prognostic role for treatment-related mortality and for a variety of allo- and CART-specific endothelial complications were established. However, the exact relationship of EASIX and other markers with endothelial cell biology are not known and require further clarification. Primary aims are to demonstrate that EASIX represents a systemic response of the organism to local or systemic loss of endothelial glycocalyx as visualized by sublingual microscopy and to establish EASIX, biomarkers and in vivo microscopy of sublingual and (in perspective) recto-sigmoidal capillary beds as prognostic markers of response to anti-neoplastic therapy, treatment-related toxicity and mortality (TRM) and overall survival (OS). Secondary objectives include the creation of a comprehensive database with information on endothelial, clinical, pathological and molecular characteristics of patients with hematological malignancies as well as the establishment of a repository of biospecimens for endothelial marker analyses from patients with hematological malignancies. We hypothesize that reduced endothelial glycocalyx thickness will permit direct interactions of leukocytes and platelets with endothelial cells, resulting in cellular activation (increased LDH), loss of platelets due to activation and microembolism, and ensuing kidney damage. As a first prospective analysis, we will answer the question if EASIX and serum endothelial biomarkers correlate with sublingual glycocalyx thickness, and if these parameters combine to predict outcome after anti-neoplastic therapy including alloSCT and CART.