Donor‐derived cell‐free DNA is associated with cardiac allograft vasculopathy

Holzhauser, Luise; Clerkin, Kevin J.; Fujino, Takeo; Alenghat, Francis J.; Raikhelkar, Jayant; Kim, Gene; Sayer, Gabriel; Uriel, Nir

doi:10.1111/ctr.14206

Cited by 20 publications

(16 citation statements)

References 56 publications

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“…For dd-cfDNA, the D-OAR trial also reported a similar false positive rate of 91% when using the cutoff value of .2%. Allograft vasculopathy or any ischemic injury can raise the level of dd-cfDNA, 14 We acknowledge several limitations in our study. First, this is a single-center study with limited participants.…”

Section: Discussionmentioning

confidence: 96%

Initiation of noninvasive surveillance for allograft rejection in heart transplant patients > 1 year after transplant

Kewcharoen

Kim

Cummings

et al. 2021

Clinical Transplantation

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Background: Gene expression profiling (GEP) and donor-derived, cell-free DNA (dd-cfDNA) measurement are alternative methods to endomyocardial biopsy (EMB) to monitor for rejection following heart transplantation. We aim to describe our use of GEP and dd-cfDNA in heart transplant recipients > 1-year post-transplantation.Methods: This is a single-center, retrospective study in post-transplant recipients. For patients who were > 1-year post-transplantation and deemed to be at elevated clinical risk for rejection, we collected both GEP and dd-cfDNA every 3 months. Baseline characteristics including GEP, dd-cfDNA levels, rejection episodes, and number of biopsies were obtained.Results: Since July 2019, there were 18 patients being followed with GEP and dd-cfDNA who were > 1-year post-transplantation. Nine EMBs had been performed in seven patients due to as follows; three due to elevated GEP ({greater than or equal to} 34), one due to elevated dd-cfDNA ({greater than or equal to} .20%), two due to elevations of both GEP and dd-cfDNA, two due to clinical rejection and one to follow up a post rejection episode. One of the two biopsies due to elevations of both GEP and dd-cfDNA showed acute cellular rejection grade 2R. None of the biopsies due to either an elevation in the GEP or dd-cfDNA revealed any significant rejection. Conclusion:In this study, the use of both GEP and dd-cfDNA led to an increased number of EMB in patients > 1-year post-transplantation. Further studies are needed to validate these findings and evaluate long-term consequences of these diagnostic tests in this populationallograft rejection, donor-derived cell-free dna, gene expression profiling, heart transplant INTRODUCTIONFollowing cardiac transplantation, the treatment goal is to prevent allograft rejection while minimizing the side effects of immunosuppressive therapy. 1 With timely detection of rejection and appropriate adjustment of immunosuppression, adult recipients can expect a

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Section: Discussionmentioning

confidence: 96%

Initiation of noninvasive surveillance for allograft rejection in heart transplant patients > 1 year after transplant

Kewcharoen

Kim

Cummings

et al. 2021

Clinical Transplantation

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“…While these are “false-positive”, the increased levels of dd-cfDNA may be the result of other graft or endothelial injury that we are unable to detect in this study due to the limited follow-up time. 8 , 14 , 20 , 21 Other studies using combination of non-invasive surveillance methods in patients over 6 months post-transplant were able to avoid the need for EMBx in many more patient using combination dd-cfDNA and GEP testing than isolated GEP screening (83.9% vs. 72.2%) 22 .…”

Section: Discussionmentioning

confidence: 99%

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19

et al. 2022

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Background The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMBx) rejection surveillance in heart transplant (HT) recipients. This is the first Canadian study to assess the role for non-invasive rejection surveillance in personalizing titration of immunosuppression (IS) and patient satisfaction post-HT. Methods In this mixed methods prospective cohort study, adult HT recipients more than six months from HT had their routine EMBx replaced by non-invasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA). Demographics, outcomes of non-invasive surveillance score, hospital admissions, patient satisfaction, and health status on Medical Outcomes Study 12-item Short Form Health Survey (SF-12) were collected and analyzed using t -tests and chi-squared tests. Thematic qualitative analysis was performed for open-ended responses. Results Among 90 patients, 31 (33%) were enrolled. 36 combined tests were performed; 22 (61%) were -GEP/-dd-cfDNA, 10 (27%) had +GEP/-dd-cfDNA, 4 (11%) had -GEP/+dd-cfDNA and 0 +GEP/+dd-cfDNA. All patients with a positive dd-cfDNA (range 0.19-0.81%) underwent EMBx with no significant cellular or antibody mediated rejection. 15 cases (42%) had IS reduction and this increased to 55% in patients with negative concordant testing. Overall, patients’ reported satisfaction was 90% and on thematic analysis they were more satisfied with less anxiety during the non-invasive testing experience. Conclusions Non-invasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in heart transplant recipients, minimizing exposure for patients and providers during a global pandemic.

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“…28 In addition, a recent study noted an increase in dd-cfDNA in stable patients with cardiac allograft vasculopathy. 29 These findings expand the utility of dd-cfDNA beyond that of rejection and suggest potential future directions for its use.…”

Section: Cell-free Dnamentioning

confidence: 75%