Dd-cfDNA Levels Are Independent of Allograft Longevity in Stable Lung Transplant Recipients

Abstract

<h3>Purpose</h3> Donor-derived cell free DNA (dd-cfDNA) is a well-studied biomarker of early allograft injury, though kinetics of dd-cfDNA outside the early period is understudied. We measured levels of plasma dd-cfDNA in stable lung transplant recipients (LTRs) >2-years post-transplant to determine if dd-cfDNA varies with allograft longevity. <h3>Methods</h3> We performed a prospective, observational study of LTRs that were > 2-years post-transplant and had stable lung function. Plasma dd-cfDNA (CareDx) was measured at outpatient visits. Patients were considered at baseline if they were hospital-free in the prior 30-days, FEV1 was >90% baseline, and they were sans fever, cough, or dyspnea. Patients treated with augmented immunosuppression for ALAD / CLAD were excluded. LTRs were categorized into three allograft-age cohorts (2-3, 3-5, or > 5 years post-transplant). Statistics were performed using SSPS (IBM); chi-squared testing and ANOVA was used for binary and continuous data, respectively. <h3>Results</h3> Baseline dd-cfDNA was measured in 59 LTRs meeting inclusion criteria. Overall median dd-cfDNA was 0.45% (IQR 0.30-0.65). (Fig. 1). Median plasma dd-cfDNA was 0.51% (IQR 0.34-0.63), 0.35% (IQR 0.12-0.59), and 0.43% (IQR= 0.29-0.67) for LTRs 2-3years, 3-5 years and >5-years post-transplant, respectively (p=0.91). Baseline demographics were similar between cohorts for all variables except transplant type (Table 1). <h3>Conclusion</h3> Plasma dd-cfDNA is <1% in clinically stable LTRs > 2-years post-transplant and does not vary with allograft survival. Future studies will determine whether changes in dd-cfDNA from baseline can predict CLAD onset.