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

Abstract

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

Comparison of two donor‐derived cell‐free DNA tests and a blood gene‐expression profile test in heart transplantation

“…Because of the low prevalence of AR, the NPV without testing already starts very high at 97% in our study and 98.4% in a recent large, multi‐center observational study 14 . The low PPV has also been observed in other recent studies for dd‐cfDNA 13,28,29 . In our study, the probability of rejection for the expanded SNP assay moves from 3.0% pretest to 7.5% post‐test for a positive test and 2.2% post‐test for a negative test.…”

“… 14 The low PPV has also been observed in other recent studies for dd-cfDNA. 13 , 28 , 29 In our study, the probability of rejection for the expanded SNP assay moves from 3.0% pretest to 7.5% post-test for a positive test and 2.2% post-test for a negative test. As a result, in the setting of low AR prevalence, the value of dd-cfDNA testing is mostly derived from the high specificity.…”

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

“…12 A similar sized, J o u r n a l P r e -p r o o f single-centre trial of 37 HT recipients greater than one year post-HT had six patients require EMBx after elevation in either GEP or dd-cfDNA testing. 23 In this study, 61% of patients remained on prednisone therapy after 1 year. In the patients with elevated dd-cfDNA levels, two patients had CAV and one had CMV infection, indicating the importance of screening for alternative conditions that may be causing graft injury while using dd-cfDNA as a non-invasive surveillance method in patients at a later time-point post-transplant.…”

Evaluating threshold for donor fraction cell‐free DNA using clinically available assay for rejection in pediatric and adult heart transplantation

“…The choice of cut point can be of significance as shown by Kewcharoen et al where adults >1 year post transplant monitored by gene expression profiling and cfDNA levels using Allosure™ in fact needed more triggered biopsies, due to cfDNA results being above threshold. The majority of these triggered biopsies were negative for rejection 15 …”

“…The majority of these triggered biopsies were negative for rejection. 15 We must also address the question of optimal cut point for specific patient populations and types of rejection. It is noted that optimal cut points varied between 0.06% for adult first samples to 0.275% for pediatric first samples.…”