Epstein-Barr Virus Lymphoproliferative Disease Following Allogeneic Hematopoietic Stem Cell Transplantation: Prediction and Early Intervention

Epstein-Barr virus (EBV) has been associated with a variety of both infectious and malignant human diseases. These viruses are characterized by (B-cell) lymphotropism, their ability to establish latent infection in host cells and to induce proliferation of these latently infected cells. Approximately 90% of humans will become infected with EBV, generally without clinical evidence of disease. Primary infection usually occurs asymptomatically in childhood and results in a lifetime carrier state with periodic release of infectious virus into saliva which may cause infection of naive individuals. E.g. during adolescence, the latter type of infection may be referred to as kissing disease or Pfeiffer’s disease. EBV causes various benign syndromes, such as infectious mononucleosis, chronic active EBV infection, X-linked lymphoproliferative disease and oral hairy leukoplakia. EBV has also been associated with malignant diseases including nasopharyngeal carcinoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, and post-transplant lymphoproliferative disease (PTLD). PTLD refer to a range of hyperplastic to neoplastic lymphoid proliferations which occur after solid organ- or bone marrow transplantation, they mostly are of B-cell origin, and commonly (90%) contain EBV. The lack of early and accurate markers of EBV reactivation and disease has long hampered a timely diagnosis of post-transplant EBV lymphoproliferative disease. The introduction of polymerase chain reaction (PCR)-based assays, however, has allowed for sensitive and quantitative monitoring of viral DNA in peripheral blood samples. This thesis has addressed the question whether molecular monitoring of EBV-DNA would accurately predict for EBV-LPD and whether preventive and therapeutic strategies could be developed based on viral load monitoring.

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