INDUSTRY WORKSHOP: Donor-derived cell-free DNA for personalized immunosuppression in transplantation
Tracks
Track 1
| Wednesday, September 24, 2025 |
| 12:30 PM - 1:25 PM |
| Grand Copthorne Waterfront Hotel - Grand Ballroom I |
Overview
Delivered by Oncocyte
Details
Donor-derived cell-free DNA (dd-cfDNA) is an effective diagnostic tool for serial surveillance of allograft health. Absolute quantification of dd-cfDNA is superior to fractional determination as it is not affected by changes of total cfDNA. Recently a new dd-cfDNA test kit for quick in-house determinations (GraftAssureTM) has been developed based on ddPCR with preselected SNPs, which enables measurements of fractional abundance (%) and absolute concentration (cp/ml). Significantly elevated absolute dd-cfDNA levels (cp/ml) were found in patients with acute or chronic antibody mediated rejection (ABMR), DSA negative patients with microvascular inflammation or BK-virus nephropathy. Low-grade T-cell-mediated rejection (TCMR) (IA) without vascular injury was not well detected in plasma in contrast to high-grade TCMR. The diagnostic performance of plasma dd-cfDNA for rejection detection is in general very good for kidney, heart, lung and liver transplant recipients (range of mean values: AUC-ROC 0.79 - 0.95, sensitivity 66 - 90 %, specificity 76 - 88 %, PPV 33 - 63 %, NPV 89 - 100 %). ABMR remains a major therapeutic challenge and causes about 20 - 30 % of allograft failures. Dd-cfDNA is useful for early ABMR detection, in particular in DSA+ patients. New treatment options using CD38-targeting monoclonal antibodies (CD38 mAB) are currently evaluated and dd-cfDNA has been used successfully as a companion biomarker in patients with chronic ABMR. In a recent randomized clinical trial longitudinal dd-cfDNA monitoring was performed for ABMR detection in kidney transplant recipients. The time from study inclusion to ABMR diagnosis was on average 2.8 months in the intervention group with dd-cfDNA guided biopsy and 14.5 months in the control group with clinician guided biopsy. In contrast to ABMR there was no significant elevation of dd-cfDNA in patients with IgA nephropathy (IgAN). Based on currently available evidence Medicare provides coverage for dd-cfDNA routine testing in the US. Dd-cfDNA facilitates personalized immunosuppression and cost-effective transplant recipient surveillance with the potential to reduce premature graft loss.
Speaker
Michael Oellerich, MD, Hon MD
Distinguished Research Professor of Clinical Chemistry
University Medical Centre Goettingen
Donor-derived cell-free DNA for personalized immunosuppression in transplantation
Biography
Michael Oellerich, MD, HonMD, FAACC, FAMM, FFPath (RCPI), FRCPath, is a chemical pathologist and currently a Distinguished Research Professor at the Department of Clinical Pharmacology, Medical Faculty (UMG) of the George-August University, Göttingen, Germany. From 2012 to 2017 he had an appointment as Lower Saxony Professor of Clinical Chemistry. He was Chairman of the Department of Clinical Chemistry/Central Laboratory at UMG (1991-2012), and Dean of the Faculty of Medicine. He served as
President of national and international professional organizations (IATDMCT, DGLM, DGKL, WASPaLM). He was Editor-in-Chief of Therapeutic Drug Monitoring (2003-2018) and currently is Associate Editor of this journal. His current research interests are in the field of therapeutic drug monitoring (e.g. cfDNA in cancer and donor-derived cell-free DNA in transplantation). He has authored more than 500 publications and has
received various awards (e.g. Ludolf-Krehl Award, IATDMCT Charles Pippenger Award, WASPaLM Medal of Honor, WASPaLM Gold-Headed Cane, Sign of Honor, Professor Jordan Todoroff (BSCL). F. McCreary Prize for Interprofessional Teamwork, Genome Canada Transplant Consortium, University of British Columbia, UBC Health, Vancouver (Canada) 2022, Claus Roxin Award for Outstanding Contributions to International Liberal Academic Exchange, Munich 2023).
