209. Epstein-Barr Virus Surveillance in Lung Transplantation: Post-transplant Lymphoproliferative Disorder and Impact on Survival
Authors: Kim Andy J , Goldberg Hilary J , Thaniyavarn Tany , Kennedy John C , Coppolino Antonio , Mallidi Hari R , Mallidi Hari R , Lee Stefi F , Joyce Mary-Ruth M , Kovac Victor , Issa Nicolas C , Harris Courtney E , LaCasce Ann S , Sharma Nirmal S , Baden Lindsey R , Woolley Ann E 
Published: December 2022

Abstract

Background
Epstein-Barr virus (EBV) donor seropositive/recipient seronegative (D+/R-) status is a risk factor for post-transplant lymphoproliferative disorder (PTLD) which is associated with increased mortality post-lung transplant. The optimal surveillance strategy for PTLD post-lung transplant stratified by EBV serostatus for early diagnosis is unknown. We assessed serial EBV viral loads (VL) for early diagnosis of PTLD and compared outcomes in EBV D+/R- and R+ lung transplant recipients at our center.

Methods
A single-center retrospective study of lung transplants between January 2017 and September 2021 was performed, with a 6-month minimum follow-up. Recipient characteristics, outcomes, and serial EBV VL (biweekly months 1-3, monthly 4-12; using the cobas quantitative PCR assay on serum) were assessed.

Results
Of the 242 lung transplant recipients, 14 (6%) were EBV D+/R- and 228 (94%) were EBV R+ [Figure 1]. Median age and lung allocation score were similar between the two cohorts [Table 1]. 7 (50%) EBV D+/R- recipients had 2 consecutive, detectable EBV VL in the first-year post-transplant compared to 30 (13%) R+ recipients (p=0.002). 5 (71%) EBV D+/R- recipients with 2 consecutive, detectable EBV VL developed PTLD compared with 2 (7%) R+ recipients (p=0.001). Median weeks post-transplant for two consecutive, detectable EBV VL were 14 (IQR 7, 15) and 10 (IQR 6, 24); and median weeks post-transplant for diagnosis of PTLD were 22 (IQR 17, 31) and 17 (IQR 16, 17) for EBV D+/R- and R+, respectively. Only recipients with at least 2 consecutive, detectable VL in the first-year post-transplant developed PTLD. EBV VL level was not associated with development of PTLD. 6-month outcomes were similar between EBV D+/R- and R+. Though there were no differences in mortality at 1 and 2-years stratified by EBV serostatus, all 5 EBV D+/R- recipients with PTLD were alive 2 years post-transplant, whereas both EBV R+ PTLD recipients died &lt; 2 years post-transplant (p=0.048). Figure 1:Study cohort characteristics and PTLD outcomes based on serial EBV viral loads within the first-year post-lung transplant*7 recipients were excluded per study criteria due to having died less than 1-month post-transplant and therefore not having sufficient EBV VL testing post-transplant for this analysis.Table 1:Baseline characteristics, index hospitalization, and clinical outcomes of lung transplant recipients stratified by EBV serostatus*P-values are based on Fisher’s two-sided exact test (for categorial variables) or the Wilcoxon rank-sum test (for continuous variables).**Time to ≥2 consecutive, detectable EBV VL was calculated based on the date of the second consecutive, detectable result.

Conclusion
Two consecutive, detectable EBV VL within the first-year post-lung transplant should prompt additional work-up for the early diagnosis of PTLD in all recipients regardless of the EBV VL level or serostatus. Though the attack rate of PTLD was greater in EBV D+/R- recipients, survival outcomes were similar irrespective of serostatus.

Disclosures
Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support.