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

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. K E Y W O R D S 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)

Lung transplantation for idiopathic pulmonary fibrosis enriches for individuals with telomere-mediated disease

“…Last, the intent of this study was to perform a detailed genetic study in IPF-LTRs versus non-transplant IPF to assess for telomere-mediated disease, but not to evaluate all transplant outcomes that we and others have described in the IPF-LTR patient population. Indeed, important questions remain regarding optimization of immune suppression, for which data was not available for the entire cohort in our study, that balance susceptibilities to complications such as bone marrow dysfunction, viral infections and malignancy in IPF-LTRs in the context of telomeremediated disease (44).…”

Induction Strategies in Lung Transplantation: Alemtuzumab vs. Basiliximab a Single-Center Experience

“…We believe that this may be largely due to the higher dose of methylprednisolone in the immediate postoperative period that our basiliximab protocol requires. We also previously reported that early post-transplant lymphoproliferative disease (PTLD) is associated with alemtuzumab induction, especially EBV-mismatched groups ( 10 ). Alemtuzumab is thought to cause stronger immunosuppression, and there was concern that it could increase malignancies and infections.…”

Association of COVID-19 and other viral infections with interstitial lung diseases, pulmonary fibrosis, and pulmonary hypertension: A narrative review

“…Latent membrane protein 1 can become apparent in patients with severe IPF, and in total IPF had been identified more frequently in EBV positive patients than in healthy control groups [ 49 ]. It was also reported that an EBV infection can increase the risk of lung cancer in IPF patients [ 50 , 51 ]. In addition, the effects of EBV infections on tumorigenicity, metastasis, and TRAIL-sensitivity of non-small cell lung cancer were reported [ 52 ].…”