The Frequency of Epstein-Barr Virus Infection and Associated Lymphoproliferative Syndrome After Transplantation and Its Manifestations in Children

Abstract

Twenty cases of Epstein-Barr virus (EBV)-associated lymphoproliferative syndrome (LPS), defined by the presence of EBV nuclear antigen and/or EBV DNA in tissues, were diagnosed in 1467 transplant recipients in Pittsburgh from 1981-1985. The frequency of occurrence in pediatric transplant recipients was 4% (10/253), while in adults it was 0.8% (10/1214) (P less than .0005). The frequency of LPS in adults declined after 1983 coincidental with the introduction of cyclosporine monitoring. However there was no apparent decline of LPS in children. We describe these ten pediatric cases and one additional case of LPS in a child who received her transplant before 1981. The frequency of EBV infection in 92 pediatric liver recipients was 63%. Of these subjects, 49% were seronegative and 77% of those acquired primary infection. Of 11 cases of pediatric EBV-associated LPS, 10 were in children who had primary infection shortly before or after transplantation. These results reinforce the importance of primary EBV infection in producing LPS, which was previously shown in adults. Children are at greater risk because they are more likely to be seronegative for EBV and to acquire primary infection. Three clinical types of LPS were recognized in children. The first (5 cases) was a self-limited mononucleosislike syndrome. The second syndrome (4 cases) began similarly, but then progressed over the next two months to widespread lymphoproliferation in internal organs and death. The third type (2 cases) was an extranodal intestinal monoclonal B cell lymphoma, occurring late after primary infection.

B cell lymphoproliferative disorders following hematopoietic stem cell transplantation: risk factors, treatment and outcome

“…Indeed, it has been observed that EBVseronegative recipients of organ allografts are at increased risk of BLPD. 39 Screening of donors and recipients for EBV serostatus is not routinely performed prior to HSCT, therefore the effect of EBV serostatus on the development of BLPD is unknown. It has been claimed that antiviral prophylaxis with acyclovir prevents BLPD, 1 but our experience does not support this.…”

Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients

“…The observed differences may be related to the amount of lymphoid tissue transplanted, and the level of immunosuppressive therapy required to prevent transplant rejection [2][3][4][5] . EBV-related PTLD occurs more frequently in children owing to primary infection, while its occurrence in adults is a result of either primary infection or reactivation 6,7 . Presentation can vary from polyclonal reactive hyperplasia of B-cells, to monoclonal or polyclonal lymphomas.…”

Immunizations and infectious diseases in pediatric liver transplantation

“…When transplants are performed in young patients, there is a high likelihood that they will be seronegative for CMV and EBV and therefore susceptible to primary infections, which are more severe than infections due to reactivation. 6,7 Donor-related issues represent another set of pretransplant factors. Transplant recipients are at risk for acquiring infections that may be active or latent within the donor organ.…”

“…6,13 However, the use of CMV prophylaxis has resulted in shifting the time of presentation of CMV disease so that some patients will present with this infection after 180 days. The intermediate period is also when patients begin to present with EBV-associated PTLD 7 and Pneumocystis jirovecii pneumonia (PCP). 13 …”