Abstract Rationale Post-transplant lymphoproliferative disorder (PTLD) develops because of immunosuppression and loss of antineoplastic ability in solid organ transplant recipients, occurring in up to 9% of patients depending on the transplanted organ. It is the most common malignancy in solid organ transplant patients. EBV serodiscordence (donor-positive/recipient-negative) is the most common risk factor for PTLD. Donor-derived cell free DNA (dd-cfDNA) detects donor DNA in the recipient and is used to detect damage to the graft. It has been proposed as a tool for early identification of patients developing PTLD. Here we present a case series of solid organ transplant recipients at our transplant center with PTLD who underwent cfDNA testing. Methods We received institutional review board (IRB) approval to access Protected Health Information (PHI) for the purposes of this study. We reviewed the electronic medical records of our hospital system for all patients with the ICD-10 code D47.Z1 for PTLD from January 31, 2015, to July 30, 2025. Of this cohort, we then identified which patients had undergone testing for dd-cfDNA. Results There were 60 patients with PTLD. The male to female ratio was 1:1 with a median age of 56.5 years at the time of data collection. Solid organ transplants included 19 (32%) kidney transplant recipients, 19 (32%) liver transplant recipients, 11 (18%) heart transplant recipients, 8 (13%) lung transplant recipients, and three patients who received multiple organs. 42 (70%) patients were still alive at the time of data collection. Five patients (8.3%) had dd-cfDNA testing. Of these, four had received orthotopic heart transplants (OHT) and 1 had received simultaneous lung/liver transplant for alpha-1-antitrypsin deficiency. Among the PTLD cases, four patients had a form of Non-Hodgkin’s lymphoma, including three with diffuse large B cell lymphoma (DLBCL). Two patients had detectable levels of dd-cfDNA. One had received OHT and was diagnosed with PTLD 22 months post-transplant with dd-cfDNA of 14.7% at the time of diagnosis. The other had received a combined lung/liver transplant with PTLD diagnosis 8.5 years post-transplant and dd-cfDNA of 3.24%. Conclusions We observed elevated dd-cfDNA in two patients, raising the possibility of donor-origin disease. However, dd-cfDNA alone is not confirmatory in determining the donor origin of PTLD and remains investigational in this context. Currently dd-cfDNA is primarily used for early screening for antibody mediated rejection, and as dd-cfDNA testing is increasingly incorporated into post-transplant surveillance, future datasets may help clarify its potential association with PTLD. This abstract is funded by: None
Sinanan et al. (Fri,) studied this question.