Correlation of Serum Gasdermin-D and NLRP-3 Inflammasome Levels With GVHD Biomarkers and Endothelial Damage Markers in Graft-Versus-Host Disease

Correlation of Serum Gasdermin-D and NLRP-3 Inflammasome Levels With GVHD Biomarkers and Endothelial Damage Markers in Graft-Versus-Host Disease in AML Patients Undergoing Allogeneic Bone Marrow Transplantation

The investigators aimed to reveal the relationship between serum markers of pyroptosis, GVHD biomarkers and endothelial damage markers in patients who were planned for allogeneic stem cell transplantation for AML and developed GVHD during follow-up. Secondary outcomes of the study were to demonstrate the role of pyroptosis in the pathophysiology of GVHD and transplantation-associated endothelial injury using serum plasma samples; the efficacy of GVHD biomarkers used to demonstrate organ-specific involvement; and the efficacy of GVHD biomarkers and endothelial injury markers in predicting the development of GVHD, transplantation-associated endothelial injury and non-relapse mortality.

Study Overview

• Status: Withdrawn
• Conditions: Endothelial Dysfunction; Graft Versus Host Disease; Acute Myeloid Leukemia, Adult

Detailed Description

In the study, in patients who were planned to receive allogeneic stem cell transplantation for AML, pre-transplant period (before and after central catheter insertion) and post-transplant period (+1, +7, +14, +28, +60 and +100 days in the post-transplant period) serum pyroptosis markers (Serum Gasdermin-D and NLRP-3 Inflammasome levels), GVHD biomarkers (REG-3 alpha, ST2, ELAFIN, HGF, ILR2-alpha, CXCL 9, CXCL 10, CXCL11, BAFF, TNF-alpha, I IL8, IL6 , IL18 , I IL1-beta , IL12 , IFN-gamma) and endothelial damage markers (serums-ICAM , sE-selectin , sVCAM , ANG2 , CRP , vWF , Factor 8 , LDH , d-dimer , transaminase enzyme levels and before transplantation, The aim of this study was to determine the relationship between basic biomarkers in pyroptosis and biomarkers with high predictive value in GVHD and markers of endothelial damage in patients who develop GVHD during follow-up using nail bed capillaroscopic examination and fibroelastographic evaluation to be performed on the twenty-first and hundredth days after transplantation.The serum samples obtained will be compared with the groups of patients with and without GVHD at the planned 1-year follow-up.

Patients diagnosed with AML between 15.11.2023 and 15.11.2024 will be included in the study and a total of 2 years of clinical follow-up is planned.

In case of loss of participants during follow-up, the study planned to recruit new patients with AML who were scheduled for transplantation between November 15, 2023 and November 15, 2024.

• Study Type: Observational

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, 06000
    • Ankara University, Department of Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients aged 18 years and older who underwent allogeneic hematopoteic stem cell transplantation for AML and were followed up by Ankara University Hematology Department

Description

Inclusion Criteria:

• 18 years of age or older
• Patients with acute myeloid leukemia undergoing allogeneic bone marrow transplantation
• Patients followed up by the Department of Hematology, Ankara University Faculty of Medicine Hospitals

Exclusion Criteria:

• Patients under 18 years of age
• Patients with non-AML transplant indication
• Patients not followed up by the Department of Hematology, Ankara University Faculty of Medicine Hospitals

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Developing GVHD; Group of patients who developed GVHD during follow-up in patients who underwent allogeneic hematopoteic stem cell transplantation for AML
non-GVHD; Group of patients who did not develop GVHD during follow-up in patients who received allogeneic hematopoteic stem cell transplantation for AML

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relationship between pyroptosis, GVHD and endothelial damage in allogeneic bone marrow transplant patients	To reveal the relationship between basic biomarkers in pyroptosis and biomarkers with high predictive value in GVHD and endothelial damage markers in AML (acute myeloid leukemia) patients with allogeneic bone marrow transplantation	The pre- and post-transplant serum samples,capillaroscopic and fibroelastographic examinations will be performed for each participant at the specified time interval until post-transplant 100th day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of used GVHD biomarkers in indicating organ-specific involvement	Effect of REG-3 alpha, ELAFIN and HGFs in demonstrating organ specificity in GVHD development	The pre- and post-transplant serum samples,capillaroscopic and fibroelastographic examinations will be performed for each participant at the specified time interval until post-transplant 100th day
The effectiveness of biomarkers in predicting the development of GVHD, transplant-related endothelial injury, and non-relapse mortality	The effectiveness of the biomarkers in predicting the development of GVHD, transplantation-related endothelial damage, and non-relapse mortality in the planned one-year follow-up	The pre- and post-transplant serum samples,capillaroscopic and fibroelastographic examinations will be performed for each participant at the specified time interval until post-transplant 100th day

Collaborators and Investigators

• Sponsor: Ugur Arzu Kulu
• Investigators: Study Director: Meltem Kurt Yüksel, Ankara University, Department of Hematology

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): November 15, 2024
• Study Completion (Estimated): November 15, 2024

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Graft Versus Host Disease; Endothelial Dysfunction; NLR Family, Pyrin Domain-Containing 3 Protein; Acute Myeloid Leukemia, Adult; Pyroptotic Cell Death; Gasdermin-D
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Graft vs Host Disease
• Other Study ID Numbers: AnkaraUniversityMedicine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No