title: Post-transplant lymphoproliferative disease in lung transplantation: A nested case-control study.
abstract: Post-transplant lymphoproliferative disorder (PTLD) may compromise long-term outcome of lung transplant (LTx) recipients. A case-control study was performed, comparing LTx recipients with PTLD (n=31) to matched recipients without PTLD (Controls, n=62). Risk factors for PTLD and post-transplant outcomes were assessed. PTLD prevalence was 3.9%, time to PTLD 323 (166-1132) days; and 54.8% had early-onset PTLD versus 45.2% late-onset PTLD. At LTx, more Epstein-Barr virus (EBV)-seronegative patients were present in PTLD (42%) compared to Controls (5%) (P<.0001); most of whom had undergone EBV seroconversion upon PTLD diagnosis. EBV viral load was higher in PTLD versus Controls (P<.0001). Overall, lower hemoglobin and higher C-reactive protein levels were present in PTLD versus Controls (P<.0001). EBV status at LTx (P=.0073) and EBV viral load at PTLD (P=.0002) were the most important risk determinates for later PTLD. Patients with PTLD demonstrated shorter time to onset of chronic lung allograft dysfunction (CLAD) (P=.0006) and poorer 5-year survival post-LTx (66.6% versus 91.5%), resulting in worse CLAD-free survival (HR 2.127, 95%CI 1.006-4.500; P=.0483) and overall survival (HR 3.297 95%CI 1.473-7.382; P=.0037) compared to Controls. Late-onset PTLD had worse survival compared to early-onset PTLD (P=.021). Primary EBV infection is a risk for PTLD; which is associated with worse long-term outcome post-LTx.
authors.affiliation: Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Leyssens
authors.affiliation: Department of Hematology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Daan
authors.initials: D
authors.lastname: Dierickx
authors.affiliation: Department of Histopathology, KU Leuven, Leuven, Belgium.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Verbeken
authors.affiliation: Department of Histopathology, KU Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Respiratory Diseases, KULeuven, Leuven, Belgium.
authors.forename: Stijn E
authors.initials: SE
authors.lastname: Verleden
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Respiratory Diseases, KULeuven, Leuven, Belgium.
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.affiliation: Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.|Department of Clinical and Experimental Medicine, Division of Respiratory Diseases, KULeuven, Leuven, Belgium.
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.affiliation: Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Yserbyt
authors.affiliation: Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.|Department of Clinical and Experimental Medicine, Division of Respiratory Diseases, KULeuven, Leuven, Belgium.
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.affiliation: Department of Experimental Thoracic Surgery, KU Leuven, Leuven, Belgium.
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.affiliation: Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.|Department of Clinical and Experimental Medicine, Division of Respiratory Diseases, KULeuven, Leuven, Belgium.
authors.forename: Robin
authors.identifier: 0000-0002-3468-9251
authors.initials: R
authors.lastname: Vos
mesh_terms: D000328:Adult; D000914:Antibodies, Viral; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology; D008297:Male; D011183:Postoperative Complications / Q000821:virology*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral
keywords: EBV; PTLD; chronic lung allograft dysfunction; lung transplantation; outcome