*Purpose: Donor-derived cell-free DNA (dd-cfDNA) testing, which has been previously validated for monitoring kidney transplant (KTx) rejection, may provide an alternative to pancreas biopsy that prevents morbidity and graft loss; in turn, we sought to determine for the first time baseline dd-cfDNA levels in pancreas transplant (PTx) recipients.

*Methods: Blood samples up to 19 months post-PTx were collected from 28 participants.

*Results: 25 patients received SPK, 3 received PTA, from whom 72 dd-cfDNA samples were collected of which 58 were used for baseline calculations. Three patients were excluded for infection and 11 for rejection. No patients died. Median dd-cfDNA scores peaked at 0.53% within one-month post-transplantation (range 0.20%-2.90%; mean 1.00±0.9%), then decreased to 0.20% (range 0.03%-3.60%; mean 0.45±0.8%). Median dd-cfDNA was 0.20% in patients without infection (range 0.03%-3.60%; mean 0.49±0.7%), and 2.3% with infection (range 1.10%-4.40%; mean 2.60±1%). Five patients underwent pancreas biopsy for cause (elevated lipase). Of these, three showed acute T cell mediated rejection (rejection rate 12%). The median dd-cfDNA score was higher with rejection (0.73%).

*Conclusions: While median and mean levels of normal dd-cfDNA in KTx recipients are currently defined as <1.0%, baseline dd-cfDNA levels among PTx recipients show a median level of <1.0%, but a higher mean, particularly within one-month post-transplantation (1.00±0.9%). Elevation in dd-cfDNA may also correlate with pancreas rejection. Confirmation of these correlations and definition of normal cutoffs will require accruing more patients to our study.

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