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

NCT06715046 | Recruiting

• 1 other identifier: P2022ZRF5H
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

cfDNA; methylation; epigenetic profile; HSCT; liquid biopsy

Outcome Measures

Primary Outcomes (1)

• Epigenetic profiling of cfDNA in patients developing GVHD

  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.

  From enrollment to the end of post-HSCT follow-up of 12 months

Secondary Outcomes (5)

• Epigenetic profiling of cfDNA in patients developing post-HSCT infections

  From enrollment to the end of post-HSCT follow-up of 12 months

• Epigenetic profiling of cfDNA in patients with engraftment failure

  From enrollment to the end of post-HSCT follow-up of 12 months

• Epigenetic profiling of cfDNA in relapsing patients

  From enrollment to the end of post-HSCT follow-up of 12 months

• 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

Study Arms (5)

GVHD patients

This group gathers all the patients that eventually develop GVHD

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

Control patients

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

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

Infection patients

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

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

Relapse patients

This group gathers all the patients that relapse after HSCT

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

TAD/SOS patients

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

Interventions

Sample collation for cfDNA methylation analysis DIAGNOSTIC_TEST

Sample collation for cfDNA methylation analysis

Control patients; GVHD patients; Infection patients; Relapse patients

Sample collection for EV phenotype analysis DIAGNOSTIC_TEST

Analysis of the EV phenotype to evaluate their potential value as markers for GVHD, relapse and engraftment.

Control patients; GVHD patients; Infection patients; Relapse patients

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

Patients will be enrolled at the Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan and at the SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital in Turin.

You may qualify if:

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

You may not qualify if:

• Patients can not be 17 years old or yunger

Sponsors & Collaborators

• University of Turin, Italy: lead
• IRCCS San Raffaele: collaborator

Study Sites (2)

Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan

Milan, Milan, 10132, Italy

RECRUITING

SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital

Turin, Turin, 10126, Italy

RECRUITING

Related Publications (5)

• Wang X, He B. Insight into endothelial cell-derived extracellular vesicles in cardiovascular disease: Molecular mechanisms and clinical implications. Pharmacol Res. 2024 Sep;207:107309. doi: 10.1016/j.phrs.2024.107309. Epub 2024 Jul 14.

  PMID: 39009292 BACKGROUND

• Jodele S, Dandoy CE, Sabulski A, Koo J, Lane A, Myers KC, Wallace G, Chima RS, Teusink-Cross A, Hirsch R, Ryan TD, Benoit S, Davies SM. Transplantation-Associated Thrombotic Microangiopathy Risk Stratification: Is There a Window of Opportunity to Improve Outcomes? Transplant Cell Ther. 2022 Jul;28(7):392.e1-392.e9. doi: 10.1016/j.jtct.2022.04.019. Epub 2022 Apr 29.

  PMID: 35490975 BACKGROUND

• Avni B, Neiman D, Shaked E, Gal-Rosenberg O, Grisariu S, Kuzli M, Avni I, Fracchia A, Stepensky P, Zuckerman T, Lev-Sagie A, Fox-Fisher I, Piyanzin S, Moss J, Salpeter SJ, Glaser B, Shemer R, Dor Y. Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers. J Clin Invest. 2024 Jan 16;134(2):e163541. doi: 10.1172/JCI163541.

  PMID: 37971879 BACKGROUND

• Oellerich M, Budde K, Osmanodja B, Bornemann-Kolatzki K, Beck J, Schutz E, Walson PD. Donor-derived cell-free DNA as a diagnostic tool in transplantation. Front Genet. 2022 Oct 21;13:1031894. doi: 10.3389/fgene.2022.1031894. eCollection 2022.

  PMID: 36339004 BACKGROUND

• Cheng AP, Cheng MP, Loy CJ, Lenz JS, Chen K, Smalling S, Burnham P, Timblin KM, Orejas JL, Silverman E, Polak P, Marty FM, Ritz J, De Vlaminck I. Cell-free DNA profiling informs all major complications of hematopoietic cell transplantation. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2113476118. doi: 10.1073/pnas.2113476118.

  PMID: 35058359 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will undergo cfDNA extraction. Resulting sample will be analyzed for the purposes of the study.

MeSH Terms

Conditions

Graft vs Host Disease; Hepatic Veno-Occlusive Disease

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Immune System Diseases; Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Central Study Contacts

Silvia Deaglio, MD/PhD

CONTACT

+39 0116709535; silvia.deaglio@unito.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medical Genetics

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 4, 2024
• Study Start: January 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 4, 2024

Record last verified: 2024-11

Locations

IT (2)