Active Epstein-Barr virus infection after allogeneic stem cell transplantation: re-infection or reactivation?

Recipients of allogeneic stem cell transplants (SCT) often show active Epstein-Barr virus (EBV) infection, which may progress to EBV-associated lymphoproliferative disorders. It is not known whether these EBV infections are true reactivations of the endogenous EBV strain or re-infections with an exogenous EBV strain. Fifty-three recipients of matched related or matched unrelated donor grafts were studied. EBV monitoring was based on a realtime TaqMan EBV DNA polymerase chain reaction (PCR) assay in plasma. In 17 patients, EBV DNA PCR monitoring was performed in peripheral blood mononuclear cells (PBMCs) as well. Mouth washings (MWs) were collected pre-transplant from all patients and family donors. Both pre-transplant EBV DNA from MWs and post-transplant EBV DNA from plasma or PBMCs were successfully obtained in 6 patients. A nested PCR targeting the EBV latent membrane protein-1 C-terminus gene was used to determine sequence variations enabling EBV strain typing. In 3 of 6 patients, the post-transplant EBV sequence pattern differed from the pre-transplant pattern, indicating a re-infection post-transplant with an exogenous strain instead of a reactivation of the original endogenous EBV strain. In the other 3 patients, the endogenous strain was identified. Active EBV infection resulting from re-infection was more severe compared with active EBV infection because of reactivation. In conclusion, active EBV infections after allogeneic SCT frequently result from re-infection with an exogenous EBV strain instead of a true reactivation of the endogenous strain and are potentially more severe.