Early findings after integration of donor-derived cell-free DNA into clinical care following pediatric heart transplantation.

Abstract

Endomyocardial biopsy (EMB) is costly and discomforting yet remains a key component of surveillance after pediatric heart transplantation (HT). Donor-derived cell-free DNA (dd-cfDNA) has been histologically validated with high negative predictive value, offering an alternative to surveillance EMB (sEMB). We implemented an alternative surveillance protocol using commercially available dd-cfDNA assays in place of sEMB after pediatric HT. Recipients ≧7months post-HT with reassuring clinical assessment were referred for dd-cfDNA. When not elevated above the manufacturers' threshold, sEMB was deferred. Subsequent clinical status and results of follow-up EMB were analyzed. Over 17months, 58 recipients [34% female, median age at HT 3.1years (IQR 0.6-10.6)] had dd-cfDNA assessed per protocol. Median age was 14.8years (8.4-18.3) and time from HT 6.0years (2.2-11.2). Forty-seven (81%) had non-elevated dd-cfDNA and 11 (19%) were elevated. During a median of 8.7months (4.2-15), all are alive without allograft loss/new dysfunction. Among those with non-elevated dd-cfDNA, 24 (51%) had subsequent sEMB at 12.1months (6.9-12.9) with 23showing no acute rejection (AR): grade 0R/pAMR0 (n=16); 1R(1A)/pAMR0 (n=7). One had AR (grade 2R(3A)/pAMR0) on follow-up sEMB after decreased immunosuppression following a diagnosis of PTLD. All 11 with elevated dd-cfDNA had reflex EMB at 19days (12-32) with AR in 4: grade 1R(1B-2)/pAMR0 (n=3); 1R(1B)/pAMR2 (n=1). dd-cfDNA assessment in place of selected, per-protocol EMB decreased surveillance EMB by 81% in our pediatric HT recipient cohort with no short-term adverse outcomes. Individual center approach to surveillance EMB will influence the utility of these findings.