Evaluation of Epstein-Barr Viral Loads As a Predictor of Development of Post-Transplant Lymphoproliferative Disorder

Prediction of post-transplant lymphoproliferative disorder (PTLD) after pediatric lung transplant remains difficult. Use of Epstein-Barr virus (EBV) viral loads (VL) in whole blood (WB) has been poorly predictive, while use of bronchoalveolar lavage (BAL) fluid has been suggested to have enhanced utility. The NIH-sponsored Clinical Trials in Organ Transplantation in Children (CTOTC-03) obtained serial quantitative measurements of EBV viral load in both WB and BAL fluid after pediatric lung transplantation. Samples were collected at scheduled intervals and with symptomatic events for two years post-transplant. Donor and recipient EBV serostatus (D/R) was recorded. Descriptive statistics, contingency analyses, and Kaplan-Meier analyses interrogated for a relationship between EBV VL and the development of PTLD. Of 61 patients, 34 (56%) had a detectable EBV VL (at least once in either WB or BAL). EBV D+ patients more often had a positive VL (D+/R-: 13/18; D+/R+: 14/25) compared to EBV D- patients (D-/R+:1/5). However, this was only statistically significant difference was for WB (p=0.025) and not BAL (p=0.08).Interestingly, 5/12 D-/R- patients developed EBV during the study period indicating potential community acquisition or inaccurate serostatus assignment. No D-/R- with EBV VL developed PTLD. All 4 who developed PTLD were a subset of the 13 D+/R- EBV patients with a positive VL. In D+/R-, EBV BAL VL in those with PTLD was a mean of 904 copies/mL (range 16-3226) compared to those without PTLD (2292; range 13-14624). Neither the time to first EBV VL nor the VL quantity in BAL or WB was statistically different between those with and without PTLD. Donor EBV seropositivity was associated with increased risk of positive WB EBV VL. Neither WB nor BAL EBV VL was predictive of the development of PTLD, regardless of EBV serostatus in this prospective pediatric lung transplant cohort. This minimizes the impact of comprehensive monitoring of WB and BAL to predict PTLD.