Clinical trial NCT06715046: Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
Collaborators: name: IRCCS San Raffaele
First posted: 2024-12-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Epigenetic profiling of cfDNA in patients developing GVHD
timeFrame: From enrollment to the end of post-HSCT follow-up of 12 months
Secondary outcomes:
measure: Epigenetic profiling of cfDNA in patients developing post-HSCT infections
timeFrame: From enrollment to the end of post-HSCT follow-up of 12 months
measure: Epigenetic profiling of cfDNA in patients with engraftment failure
timeFrame: From enrollment to the end of post-HSCT follow-up of 12 months
measure: Epigenetic profiling of cfDNA in relapsing patients
timeFrame: From enrollment to the end of post-HSCT follow-up of 12 months
measure: Epigenetic profiling of cfDNA in patients developing transplant associated microangiopathy or sinusoidal obstruction
timeFrame: From enrollment to the end of post-HSCT follow-up of 12 months
measure: Evaluation of EV phenotype
timeFrame: From enrollment to the end of post-HSCT follow-up of 12 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan
city: Turin
country: Italy
facility: SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital
Study officials:
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.