Epstein–Barr virus-associated lymphoproliferative disease after allogeneic haematopoietic stem cell transplantation: molecular monitoring and early treatment of high-risk patients

Abstract

Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a rare but serious complication in recipients of allogeneic stem cell transplants. An overview is given of the incidence, monitoring and (early) treatment of EBV-LPD. The most important risk factor for EBV-LPD is the use of in-vivo T-cell depletion with antithymocyteglobulin. In addition, alternative donor stem cell transplantation is associated with an increased risk for EBV-LPD. Monitoring of EBV DNA in high-risk patients and subsequent early treatment is very successful, resulting in a low EBV-associated mortality. The monitoring of EBV-specific cytotoxic T lymphocytes might further increase the positive predictive value of EBV DNAemia for EBV-LPD. Once overt EBV-LPD has been diagnosed, rituximab treatment is indicated, guided by monitoring of EBV DNA. The infusion of donor lymphocytes is highly effective, but may be complicated by graft-versus-host disease. Therefore, the infusion of T cells, which have been depleted of alloreactive cells, is currently receiving attention. EBV DNA levels should be monitored in patients with high-risk features. Early treatment may be instituted at predefined DNA levels (preemptive approach) or at the earliest signs of LPD (prompt approach). Stepwise treatment guided by EBV DNA, including interruption of immunosuppression, rituximab, and adoptive T-cell immunotherapy may all add to the low mortality currently associated with LPD following allogeneic stem cell transplantation.