Epstein-Barr virus-associated posttransplant lymphoproliferative disorder after allogeneic stem cell transplantation

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder is an increasingly life-threatening complication after allogeneic stem cell transplantation with the use of more complex transplant procedures.

Reduced intensity conditioning regimens in combination with in-vivo or ex-vivo T-cell depletion are particularly important risk factors. Prospective monitoring of EBV viremia by real-time quantitative polymerase-chain reaction (PCR) should be performed after high-risk allogeneic stem cell transplantation. However, lack of standardization and concerns about sensitivity and low positive-predictive value challenge the interpretation of PCR monitoring. Preemptive treatment is feasible and can reduce EBV-related mortality but may lead to overtreatment in some patients. Readily available rituximab and methods of adoptive transfer of T-cells are valuable tools. Rituximab is probably the most attractive agent showing the most robust data in this setting. Rituximab seems to offer a good balance between efficacy and toxicity for the treatment of established EBV-associated posttransplant lymphoproliferative disorder. But most often there is a need to combine with adoptive immunotherapy with T-cells to maintain long-term disease control, with either simple unmanipulated donor lymphocyte infusion or more specific and complex adoptive EBV-specific cytotoxic T-cells.

EBV-associated posttransplant lymphoproliferative disorder can often be prevented or treated, especially in earlier stages. The specific role and timing of the different treatment strategies need to be defined.