Identification of Epstein-Barr Virus Related Risk Factors for the Occurrence of Post-Transplant Lymphoproliferative Disorder in Lung Transplant Recipients

Abstract

<h3>Purpose</h3> Post-transplant lymphoproliferative disorder (PTLD) is the second most common malignancy in solid organ transplantation. Based on recent registry data, ≈ 1.1% of lung transplants (LTx) develop PTLD within the first year. PTLD confers significant morbidity and mortality and has been associated with Epstein-Barr virus (EBV) infection. The threshold for EBV viremia predictive of PTLD is unknown. In the current study we examined risk factors for PTLD development and the relationship between EBV viremia and PTLD in LTx was assessed. <h3>Methods</h3> A single-center, retrospective review of all LTx recipients from 1/1/2009 - 7/31/2019 with EBV viremia was conducted. All patients (pts) with at least one positive EBV PCR test were reviewed for EBV viremia progression and PTLD occurrence. PTLD was confirmed by review of oncology notes, biopsy results, computed tomography and positron emission tomography scans. <h3>Results</h3> One hundred and forty-seven pts were included. Thirty-four (24.8%) underwent work-up for PTLD, of whom ten were diagnosed with PTLD. Median time from transplant to EBV viremia was 368 days (IQR 111-1201) with PTLD diagnosis occurring at a median of 521 days (IQR 150-741) after LTx. The PTLD(+) group had a higher baseline median EBV PCR of 2613 copies/mL (IQR 680-6099) vs 528 copies/mL (IQR 369-930) in PTLD(-) pts and an increased number of positive PCRs; 3.5 (IQR 2-10) vs 1 (IQR 1-2). In patients with EBV IgG data available, (<i>n</i>=66), Donor(+)/Recipient(-) pts were more likely to develop PTLD than other groups, RR = 18.3 (95% CI 3.93, 85.32); p<0.001. A cut-point analysis of EBV viral load determined that pts with a baseline EBV viral load >1930 copies/mL had a significantly higher risk of PTLD development, RR = 31.03 (95 %CI 9.44, 102.02); p<0.001. <h3>Conclusion</h3> EBV mismatch, higher viral loads, and persistence of viremia may be indicative of PTLD development. Patients with an EBV viral load >1930 copies/ml may benefit from closer surveillance.