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

University of Turin

Status: Enrolling

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

Treatments: Diagnostic Test: Sample collation for cfDNA methylation analysis; Diagnostic Test: Sample collection for EV phenotype analysis

Study type: Observational

Funder types: Other

Identifiers

NCT06715046

P2022ZRF5H

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

30 participants in 5 patient groups

GVHD patients

Description:

This group gathers all the patients that eventually develop GVHD

Treatment:

Diagnostic Test: Sample collection for EV phenotype analysis

Diagnostic Test: Sample collation for cfDNA methylation analysis

Control patients

Description:

This group gathers all the patients that will not develop post-HSCT complications and show no signs of relapse.

Treatment:

Diagnostic Test: Sample collection for EV phenotype analysis

Diagnostic Test: Sample collation for cfDNA methylation analysis

Infection patients

Description:

This group gathers all the patients that develop post-HSCT infections

Treatment:

Diagnostic Test: Sample collection for EV phenotype analysis

Diagnostic Test: Sample collation for cfDNA methylation analysis

Relapse patients

Description:

This group gathers all the patients that relapse after HSCT

Treatment:

Diagnostic Test: Sample collection for EV phenotype analysis

Diagnostic Test: Sample collation for cfDNA methylation analysis

TAD/SOS patients

Description:

This goup gathers patients presenting with transplant associated microangiopathy or sinusoidal obstruction.