Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation

Recruiting

• Conditions: GVHD - Graft-Versus-Host Disease; Infections After HSCT; Transplant Associated Microangiopathy TAM; Sinusoidal Obstruction Syndrome (SOS); HSCT Engraftment

• Registration Number: NCT06715046
• Lead Sponsor: University of Turin, Italy

Brief Summary

Allogeneic hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for people with severe blood-related diseases. However, it comes with serious risks, including a condition called graft-versus-host disease (GVHD), where the transplanted cells attack the patient's body. GVHD can occur in about 50% of patients acutely and 35% in a chronic form, potentially affecting organs like the skin, liver, and gastrointestinal system. Currently, doctors diagnose GVHD based on symptoms, as there are no easy tests available.

Infections can also be a problem after HSCT, as dormant viruses may reactivate. These infections are monitored using specialized tests. Additionally, doctors use advanced methods, like analyzing minimal residual disease (MRD) and chimerism, to check for the risk of the original disease coming back. MRD is tracked by looking for specific genetic markers of the disease in the patient's blood or bone marrow.

Another emerging tool involves analyzing cell-free DNA (cfDNA)-tiny fragments of DNA found in bodily fluids that come from dying cells. This technique, called liquid biopsy, has been revolutionary in areas like cancer detection, pregnancy testing, and organ transplants. For example, in organ transplants, cfDNA can indicate early signs of rejection, helping reduce the need for invasive biopsies.

In HSCT, the use of cfDNA to monitor complications like GVHD or relapse has not been fully explored. This pilot study aims to investigate whether analyzing cfDNA using a technique called epigenomic profiling can help detect acute GVHD, as well as other post-transplant issues like infections, disease relapse, and chronic GVHD. The goal is to compare cfDNA analysis to current testing methods to see if it offers better or earlier detection of complications.

This research could pave the way for improved, less invasive monitoring of HSCT patients, potentially leading to better outcomes and fewer complications.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-31
• Status Verified: 2024-11
• Study First Submitted: 2024-11-27
• Study First Submitted QC: 2024-11-27
• Last Update Submitted: 2024-11-27
• Study First Posted: 2024-12-04
• Last Update Posted: 2024-12-04
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patient must be affected by an hematological malignancy requiring hematopoietic stem cell transplantation (HSCT).

Exclusion Criteria

• Patients can not be 17 years old or yunger

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Epigenetic profiling of cfDNA in patients developing GVHD	From enrollment to the end of post-HSCT follow-up of 12 months	Analysis of cfDNA methylation patterns in GVHD patients vs controls to define potential marker regions to be translationally utilized for early detections of the disease.

Secondary Outcome Measures

Name	Time	Method
Epigenetic profiling of cfDNA in patients developing post-HSCT infections	From enrollment to the end of post-HSCT follow-up of 12 months	Analysis of cfDNA methylation patterns in patients developing post-HSCT transplantation infections vs controls to define potential marker regions to be translationally utilized for early detections of the condition.
Epigenetic profiling of cfDNA in patients with engraftment failure	From enrollment to the end of post-HSCT follow-up of 12 months	Analysis of cfDNA methylation patterns in patients with engraftment failure vs controls.
Epigenetic profiling of cfDNA in relapsing patients	From enrollment to the end of post-HSCT follow-up of 12 months	Description: Analysis of cfDNA methylation patterns in relapsing patients vs controls.
Epigenetic profiling of cfDNA in patients developing transplant associated microangiopathy or sinusoidal obstruction	From enrollment to the end of post-HSCT follow-up of 12 months
Evaluation of EV phenotype	From enrollment to the end of post-HSCT follow-up of 12 months	Evaluation of circulating vesicle phenotype in as potential biomarker for GVHD, engraftment and relapse.

Trial Locations

Locations (2)

Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan; 🇮🇹 Milan, Italy

SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital; 🇮🇹 Turin, Italy