The Endothelial Cell Dysfunction and Outcome Project for Hematological Neoplasms

NCT05502887 | Recruiting

• 1 other identifier: EndoCDO-H
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematological Neoplasm; Endothelial Dysfunction

Keywords

endothelial cells; biomarkers; endothelial activation and stress index (EASIX); endothelial complications; non-relapse mortality; in vivo microscopy

Outcome Measures

Primary Outcomes (1)

• overall survival

  Time period between date of informed consent to alive at last follow-up or death

  observation peroid 10 years

Secondary Outcomes (3)

• side effects

  observation peroid 10 years

• Treatment adaptation

  observation peroid 10 years

• endothelial glycocalyx

  observation peroid 10 years

Study Arms (1)

Researched Group

All patients with newly diagnosed or preexistent hematological neoplasms at participating centers are intended to be registered within EndoCDO-H. Prior to inclusion, patients have to give their written informed consent.

Diagnostic Test: Sublingual in vivo microscopy with the Glycocheck microscope

Interventions

Sublingual in vivo microscopy with the Glycocheck microscope DIAGNOSTIC_TEST

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.

Researched Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients with newly diagnosed or preexistent hematological neoplasms at participating centers are intended to be registered within EndoCDO-H. Prior to inclusion, patients have to give their written informed consent.

You may qualify if:

• Suspected or proven diagnosis of hematological neoplasms according to the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues;
• Age ≥18 years;
• Ability to understand nature and individual consequences of the registry;
• Written informed consent;
• Subjects who are physically or mentally capable of giving consen.

You may not qualify if:

• \- Severe neurological or psychiatric disorder interfering with the ability to give written informed consent.

Sponsors & Collaborators

• Prof. Dr. Thomas Luft: lead

Study Sites (1)

Department of Internal Medicine V, Heidelberg University Hospital

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Related Publications (5)

• Luft T, Dreger P, Radujkovic A. Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation. Bone Marrow Transplant. 2021 Oct;56(10):2326-2335. doi: 10.1038/s41409-021-01390-y. Epub 2021 Jul 12.

  PMID: 34253879 BACKGROUND

• Luft T, Wendtner CM, Kosely F, Radujkovic A, Benner A, Korell F, Kihm L, Bauer MF, Dreger P, Merle U. EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients. Front Immunol. 2021 Jun 23;12:634416. doi: 10.3389/fimmu.2021.634416. eCollection 2021.

  PMID: 34248931 BACKGROUND

• Luft T, Benner A, Jodele S, Dandoy CE, Storb R, Gooley T, Sandmaier BM, Becker N, Radujkovic A, Dreger P, Penack O. EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. Lancet Haematol. 2017 Sep;4(9):e414-e423. doi: 10.1016/S2352-3026(17)30108-4. Epub 2017 Jul 18.

  PMID: 28733186 BACKGROUND

• Luft T, Benner A, Terzer T, Jodele S, Dandoy CE, Storb R, Kordelas L, Beelen D, Gooley T, Sandmaier BM, Sorror M, Zeisbrich M, Radujkovic A, Dreger P, Penack O. EASIX and mortality after allogeneic stem cell transplantation. Bone Marrow Transplant. 2020 Mar;55(3):553-561. doi: 10.1038/s41409-019-0703-1. Epub 2019 Sep 26.

  PMID: 31558788 BACKGROUND

• Simons L, Alasfar L, Qadoura M, Buhl J, Sunderer F, Korell F, Ikonomidis I, Dietrich M, Seidlitz S, Vink H, Maier-Hein L, Schmitt M, Schlenk RF, Carsten Muller-Tidow, Dreger P, Luft T. Comprehensive assessment of endothelial dysfunction before cellular therapy: EASIX, local imaging, and systemic biomarkers. Blood Vessel Thromb Hemost. 2025 Sep 10;2(4):100105. doi: 10.1016/j.bvth.2025.100105. eCollection 2025 Nov.

  PMID: 41334245 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood and bone marrow samples, plasma and serum including liquid biopsies (cfDNA) are collected

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Prof. Dr. Thomas Luft

  Heidelberg University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof. Dr. Thomas Luft

CONTACT

+49 06221/56 8030; Thomas.Luft@med.uni-heidelbe

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: August 16, 2022
• Study Start: September 1, 2022
• Primary Completion (Estimated): June 7, 2027
• Study Completion (Estimated): June 7, 2032
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)