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| Name | Class |
|---|---|
| IRCCS San Raffaele | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GVHD patients | This group gathers all the patients that eventually develop GVHD |
| |
| Control patients | This group gathers all the patients that will not develop post-HSCT complications and show no signs of relapse. |
| |
| Infection patients | This group gathers all the patients that develop post-HSCT infections |
| |
| Relapse patients | This group gathers all the patients that relapse after HSCT |
| |
| TAD/SOS patients | This goup gathers patients presenting with transplant associated microangiopathy or sinusoidal obstruction. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sample collation for cfDNA methylation analysis | Diagnostic Test | Sample collation for cfDNA methylation analysis |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Epigenetic profiling of cfDNA in patients developing post-HSCT infections | 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. | From enrollment to the end of post-HSCT follow-up of 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Silvia Deaglio, MD/PhD | Contact | +39 0116709535 | silvia.deaglio@unito.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unità di Ematologia e Trapianto di Midollo Osseo e Oncoematologia of the San Raffaele Hospital in Milan | Recruiting | Milan | Milan | 10132 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39009292 | Background | 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. | |
| 35490975 | 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. |
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Blood samples will undergo cfDNA extraction. Resulting sample will be analyzed for the purposes of the study.
| 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. |
|
| Epigenetic profiling of cfDNA in patients with engraftment failure | Analysis of cfDNA methylation patterns in patients with engraftment failure vs controls. | From enrollment to the end of post-HSCT follow-up of 12 months |
| Epigenetic profiling of cfDNA in relapsing patients | Description: Analysis of cfDNA methylation patterns in relapsing patients vs controls. | 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 | Evaluation of circulating vesicle phenotype in as potential biomarker for GVHD, engraftment and relapse. | From enrollment to the end of post-HSCT follow-up of 12 months |
| SS Trapianto allogenico e terapie cellulari, SC Ematologia U of the Città della Salute e della Scienza Hospital | Recruiting | Turin | Turin | 10126 | Italy |
| 37971879 | 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. |
| 36339004 | 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. |
| 35058359 | 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. |
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| D006504 | Hepatic Veno-Occlusive Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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