406.1: An Initial Analysis of the Baseline Levels of dd-cfDNA After Pancreas Transplantation: A Prospective Study From High-volume Centers in the United States

Abstract

Introduction: Donor-derived cell-free DNA (dd-cfDNA) testing, which has been validated for monitoring kidney transplant (KTx) rejection, may provide an alternative to pancreas biopsy that prevents morbidity and graft loss. We determined, for the first time, dd-cfDNA levels in pancreas transplant (PTx) recipients with and without rejection. Methods: From N=101 participants, n=161 dd-cfDNA blood samples up to 50 months post-transplant were collected. Results: 78 (77%) participants received SPK, 21 (21%) received PTA, 1 (1%) received PAK, and 1 (1%) received KTA. Mean, median, and mode of dd-cfDNA levels in all participants are 0.61±0.98%, 0.28%, and 0.20%. Mean baseline dd-cfDNA level of participants without rejection was 0.46±0.70% [N=96 (95%), n=128 (80%)]. Mean baseline dd-cfDNA levels peaked at 1.45±1.54% within one-month post-transplantation. Compared to baseline, mean dd-cfDNA levels of participants with any rejection were 1.22±0.98% [N=6 (6%), n=33 (20%), p=0.02]. For those with KTx ACR, mean dd-cfDNA levels was 1.54±1.94% [N=2 (2%), n=12 (7%), p=0.11]. For those with PTx rejections overall, ACR, and AMR, mean dd-cfDNA levels were 1.23±1.58% [N=4 (4%), n =24 (15%), p=0.042], 1.51±1.81% [N=3 (3%), n=17 (11%), p=0.02], and 0.54±0.30% [N=1 (1%), n=7 (4%), p=0.49].Discussion: The mean baseline dd-cfDNA level for PTx recipients in this study is <1.0%, which is consistent with the KTx rejection threshold dd-cfDNA value in KTx recipients of >1.0% in existing literature. However, the natural course of baseline dd-cfDNA seems to transiently elevate >1.0% at one-month post-transplant. This study shows that dd-cfDNA elevation also correlates with pancreas rejection. The mean dd-cfDNA level in PTx rejections overall and PTx ACR specifically are >1.0% and significantly different from baseline levels. In PTx patients, dd-cfDNA is a promising biomarker for PTx rejection. Accruing new and following existing participants will confirm these findings and help define a rejection threshold. Funding support from CareDx for this study.