Original Clinical ScienceUse of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD)
Section snippets
Study design
We conducted an observational analysis that included subjects from two ongoing prospective cohort studies. The first study, Genome transplant dynamics (GTD) (NCT01985412), is a single center study that began in 2010 at Stanford University Hospital to evaluate the utility of plasma %ddcfDNA to monitor for acute rejection. The second study, Genomic Research Alliance for Transplantation (GRAfT) (NCT0243070), began recruitment in 2015 at three centers (the Johns Hopkins Hospital and University of
Cohort description
Ninety-nine subjects met criteria for inclusion in our analysis; however, 13 of these patients did not have available day 3 CXR or ABG data necessary to adjudicate for PGD. 86 patients were therefore included in our final analysis (Supplementary Figure S1). The mean (SD) age at transplantation was 54.3 (14.4) years and the mean (SD) Lung Allocation Score (LAS) was 44.9 (12.1). Interstitial lung disease was the most common indication for transplant (46.4%) and 70.2% of patients underwent
Discussion
This study reports two important findings supporting the use of %ddcfDNA in patients with PGD. First, from Day 1 of transplantation, %ddcfDNA correlated with the presence and severity of PGD. Second, in patients with PGD, %ddcfDNA correlated with the subsequent risk of developing CLAD. Tanaka et al. previously reported an inverse correlation between %ddcfDNA and oxygenation in a cohort of 15 patients undergoing living donor-lobar lung transplantation as well as higher levels of %ddcfDNA in
Disclosure statement
Dr. Errol Bush has received consulting fees from VeraMedica Institute for occupational/environmental exposure litigation. Dr. Kiran Khush reports receiving grants and personal fees as a scientific advisor and participant on a speaker's bureau from CareDx Inc. outside of the scope of the submitted work. Dr. Sean Agbor-Enoh receives funding from the Cystic Fibrosis Foundation, the National Institute of Health Distinguished Scholar Program and the National Heart, Lung and Blood Institute
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Short airway telomeres are associated with primary graft dysfunction and chronic lung allograft dysfunction
2023, Journal of Heart and Lung TransplantationChronic lung allograft dysfunction in 2022, past and updates
2023, Revue des Maladies RespiratoiresElevated cell-free DNA in respiratory viral infection and associated lung allograft dysfunction
2022, American Journal of TransplantationComparison of donor-derived cell-free DNA between single versus double lung transplant recipients
2022, American Journal of TransplantationCitation Excerpt :The primary clinical endpoint of this study was acute rejection, a composite outcome of acute cellular rejection (ACR) grade A2 or higher, ACR grade 1 with allograft dysfunction (>10% decline in forced expiratory volume in 1 second (FEV1)), and clinical antibody mediated rejection (AMR). All endpoints were adjudicated by centralized multidisciplinary adjudication committees blinded to %dd-cfDNA data as previously described.2,6,8 Endpoints were adjudicated using center level data to remain consistent with usual care practices.
Variability in plasma donor-derived cell-free DNA levels with CLAD more than 5-years after Lung Transplantation: Pilot data
2022, Transplantation ReportsCitation Excerpt :Diagnosis of CLAD is determined by clinical and physiologic criteria since transbronchial biopsies usually lack adequate sensitivity to provide histopathologic confirmation [3]. Donor-derived cell-free DNA (dd-cfDNA) has recently emerged as a valuable plasma biomarker that has been clinically validated for detection of acute cellular and antibody mediated rejection (AMR) in LT [4–6]. To date, studies have principally focused on estimation of the donor fraction (%dd-cfDNA) expressed as percentage of background (host) cell-free DNA (cfDNA), with thresholds validated for %dd-cfDNA during the earlier post-LT epochs.