Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival

Am J Transplant. 2020 May;20(5):1439-1446. doi: 10.1111/ajt.15756. Epub 2020 Jan 22.

Abstract

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (EBV-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 7-year period. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan-Meier analysis showed a decreased freedom from PTLD in idiopathic pulmonary fibrosis (IPF)-LTRs (P < .02). Using a multivariable Cox proportional hazards model, we found IPF (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.33-8.21, P = .01) and alemtuzumab induction therapy (HR 2.73, 95% CI 1.10-6.74, P = .03) as risk factors for PTLD, compared to EBV mismatch (HR: 34.43, 95% CI 15.57-76.09, P < .0001). Early PTLD (first year) was associated with alemtuzumab use (P = .04), whereas IPF was a predictor for late PTLD (after first year) (P = .002), after controlling for age and sex. Kaplan-Meier analysis revealed a shorter time to death from PTLD in IPF LTRs compared to other patients (P = .04). The use of alemtuzumab in EBV mismatch was found to particularly increase PTLD risk. Together, our findings identify IPF LTRs as a susceptible population for PTLD. Further studies are required to understand the mechanisms driving PTLD in IPF LTRs and develop strategies to mitigate risk.

Keywords: clinical research/practice; hematology/oncology; immunosuppression/immune modulation; immunosuppressive regimens - induction; infection and infectious agents - viral: Epstein-Barr virus (EBV); lung disease; lung transplantation/pulmonology; posttransplant lymphoproliferative disorder (PTLD).

MeSH terms

  • Epstein-Barr Virus Infections* / etiology
  • Herpesvirus 4, Human
  • Humans
  • Idiopathic Pulmonary Fibrosis* / etiology
  • Lung
  • Lymphoproliferative Disorders* / etiology
  • Retrospective Studies
  • Risk Factors
  • Transplant Recipients