The Endothelial Cell Dysfunction and Outcome Project for Hematological Neoplasms

Condition(s) studied

Investigational drug(s) / intervention(s)

Sublingual in vivo microscopy with the Glycocheck microscope: For the collection of longitudinal microscopy data, sublingual in vivo microscopy with the Glycocheck microscope will be performed at the following timepoints: 2-3 x between day (D) -28 of allogeneic HSCT or CAR T cell therapy and before start of the conditioning regimen, once between D2-D14, once between D15-28, once between D30- D100 and at the onset of endothelial complications such as acute GvHD, TMA, sepsis, VOD and IPS following allogeneic HSCT or CAR T cell therapy. Sublingual microscopy requires 15-30 minutes and is similar to sublingual temperature measurement. To this extent, a tube with a diameter of approximately 1cm carrying a microscope at the tip is inserted into the mouth and under the tongue to measure endothelial structures (blood flow through small capillaries). Biological samples are collected and processed within the established Biobank of the Internal Medicine V of the Heidelberg University Hospital.

Study summary

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.

Eligibility

Primary outcome measure(s)

• overall survival — observation peroid 10 years
  Time period between date of informed consent to alive at last follow-up or death

Trial sites (1)

Other trials for the same condition