Pleuroparenchymal Fibroelastosis in Chronic Graft-versus-Host-Disease

Abstract

<h3>Purpose</h3> Pleuroparenchymal fibroelastosis (PPFE) is a rare entity of interstitial lung disease previously reported in both lung and hematopoietic stem cell transplant (HCT) recipients. The association between PPFE and chronic Graft-versus-Host Disease (cGVHD) has not been established. <h3>Methods</h3> Patients on cGVHD protocols (NCT00092235; NCT02669251) between 10/01/2004 and 01/31/2020 were included. An independent committee of two transplant hematologists, one cardiothoracic radiologist, and three transplant pulmonologists reviewed patients' demographic and HCT information, pulmonary function tests (PFT), and thoracic CT scans. The diagnosis of PPFE was adapted from the 2013 ATS/ERS Interstitial Lung Disease Consensus Statement (Table 1). <h3>Results</h3> PPFE was diagnosed in 0.8% (3/374) of patients (Table 2). All were female with body mass index (BMI) <18.5kg/m². Patients 2 and 3 had classical Hodgkin lymphoma (cHL) with intrathoracic involvement, received bleomycin (patient 2 and 3) and mediastinal radiation (patient 2) prior to HCT. All had severe cGVHD, requiring 1-5 lines of systemic immunosuppressive therapy. Before the development of PPFE, Patients 2 and 3 had viral pneumonia, while patient 1 had no documented pulmonary infection. Lung biopsies in all patients showed non-specific inflammation and fibrosis; of note, all were performed before the definition of PPFE as a clinical entity in 2013, and did not include the pleura or subpleural parenchyma. At data cut-off (April 2021), all patients were alive. Median time from HCT to PPFE diagnosis was 5.5 years (range, 2-6.5), and median survival post-PPFE diagnosis was 7.5 years (range, 5.5-12). <h3>Conclusion</h3> PPFE is a rare, delayed complication of HCT which can be seen with concurrent cGVHD. The pathogenesis of PPFE is unclear but may be associated with the immune-mediated lung injury in cGVHD, infection, preexisting malignancy and lung-toxic treatment. Heightened clinical awareness for PPFE among the cGVHD population warrants further study.