Idiopathic Pulmonary Fibrosis Lung Transplant Recipients are at Increased Risk for Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorder

Abstract

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single-center retrospective study to evaluate the risks for PTLD in LTRs over a seven-year period. All LTRs transplanted from 2010 to 2016 were included. LTRs who died within 3 months or were lost to follow-up were excluded. Sex, age, EBV serostatus, induction agent, indication agent, and survival were collected via chart review. The primary outcome was development of PTLD. Secondary endpoints were early and late PTLD and survival. Primary and secondary outcomes were assessed using Kaplan-Meier methods and Cox proportional hazards models. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan-Meier analysis showed an increased rate of PTLD in idiopathic pulmonary fibrosis (IPF)-LTRs (p<0.02). Multivariable Cox proportional hazards modeling found IPF (HR 3.51, 95% CI 1.33-8.21, p=0.01), alemtuzumab induction therapy (HR 2.73, 95% CI 1.10-6.74, p=0.03), and EBV mismatch (HR: 34.43, 95% CI: 15.57-76.09, p<0.0001) as risk factors for PTLD. Early PTLD (first-year) was associated with alemtuzumab use (p=0.04), whereas IPF was a predictor for late PTLD (after first-year) (p=0.002), after controlling for age and sex. Kaplan-Meier analysis revealed a shorter time to death from PTLD in IPF-LTRs compared to other LTRs (p=0.04). The use of alemtuzumab in EBV-mismatch was found to particularly increase PTLD risk. IPF-LTRs are at increased susceptibility for PTLD compared to non-IPF LTRs. LTRs who received alemtuzumab induction were at increased risk for PTLD, particularly those who were EBV mismatches. Ongoing studies are being conducted to understand the mechanisms driving PTLD in IPF-LTRs and develop strategies to mitigate risk.