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Post-transplantation Lymphoproliferative Disease

Epstein-Barr Virus DNA Levels, HLA-A3, and Survival

¹ The School of Medicine, ² Department of Pathology and Laboratory Medicine, ³ Department of Microbiology and Immunology, and ⁴ Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, North Carolina

Correspondence and requests for reprints should be addressed to Robert Aris, M.D., CB# 7020, 4131 Bioinformatics Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail: aris{at}med.unc.edu

Rationale: Elevation in Epstein-Barr virus (EBV) circulating DNA has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but few published data exist in the study of lung-transplant recipients.

Objectives: To determine if elevated EBV DNA levels, in combination with other risk factors, were predictive of PTLD.

Methods: We conducted a retrospective, single-center study examining all lung transplant recipients (n = 296) and EBV DNA levels (n = 612) using real-time TaqMan polymerase chain reaction. There were 13 cases of PTLD overall, of which 5 occurred in the era of EBV DNA monitoring.

Measurements and Main Results: EBV DNA levels were distributed differently among seropositive and seronegative patients, with the latter having higher values (P < 0.0001). Among the cohort of pretransplantation seropositive patients, there was one diagnosed with PTLD. The EBV DNA level in this patient was elevated at the time of PTLD diagnosis (sensitivity = 100%, specificity = 100% for PTLD). Among the cohort of pretransplantation seronegative patients, there were four with a diagnosis of PTLD. In all four patients, the EBV DNA level was detectable (sensitivity = 100%, specificity = 24%), but in only two was it elevated (sensitivity = 50%, specificity = 22%). HLA-A3 expression in the recipient and/or donor conferred additional risk for PTLD among the seronegative patients (P = 0.026 to 0.003). No other PTLD risk factor was found.

Conclusions: EBV DNA levels are a useful but imperfect predictor of PTLD in patients with lung transplants. Pretransplant EBV status affected the results of the assay and should be considered when interpreting test results. HLA-A3 was strongly linked to PTLD and may be a novel marker of PTLD risk.

Key Words: lung transplantation • EBV • DNA • HLA • lymphoma • PTLD

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Post-transplant lymphoproliferative disease (PTLD) continues to be a serious problem after lung transplantation with high mortality rates. What This Study Adds to the Field Epstein-Barr virus (EBV) DNA monitoring contributes to PTLD diagnosis but results need to be evaluated in the context of pretransplant EBV serology. The expression of HLA-A3 appears to be a novel marker of PTLD risk.

 

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