Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients

Abstract

Background: Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only.

Methods: The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described.

Results: Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 10⁵ PBMC in one patient and > 1,000 copies EBV DNA/1 × 10⁵ PBMC in two patients.

Conclusion: A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD.

Figure 1

Kinetics of EBV DNAemia in a lung transplant recipient developing primary EBV infection and PTLD in the post-transplant period. The dotted line indicates EBV DNAemia levels. The dark-grey boxes indicate treatment periods. The time of PTLD diagnosis is indicated by the arrow.

Figure 2

Kinetics of EBV DNAemia and computerized tomography scan analysis in a patient with PTLD. (A) Monitoring by computerized tomography scan analysis of an intrathoracic PTLD nodule (white arrow) in a lung transplant recipient. (B) EBV DNA levels in peripheral blood mononuclear cells (PBMC), bronchoalveolar lavage (BAL) and biopsy specimens.