Epstein–Barr virus reactivation after allogeneic hematopoietic stem cell transplantation: multifactorial impact on transplant outcomes

Epstein–Barr virus (EBV) reactivation after allogeneic hematopoietic cell transplantation (allo-HCT) is one of the major concerns that may lead to fatal EBV diseases. However, updated data are needed because of the remarkable evolution of the HCT protocol and donor selection. We conducted a retrospective study that enrolled 890 allo-HCT recipients. Independent risk factors for EBV reactivation were use of antithymocyte globulin, haploidentical donor, and the presence of chronic graft-versus-host disease. The cumulative incidence of EBV reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors, respectively ( P < 0.001). Posttransplant lymphoproliferative disorders (PTLDs) occurred in seven patients. EBV reactivation was associated with inferior survival in recipients who survived more than 2 years post-HCT ( P < 0.001) but might time-dependently benefit those patients with malignancies by decreasing relapse incidence ( P = 0.046). A decreased relapse incidence was observed 1 year after HCT for recipients at first or second remission ( P = 0.042) and in the first year post-HCT for recipients with advanced diseases ( P = 0.032). We concluded that with current management, PTLDs were efficiently controlled, but EBV reactivation still had a multifactorial impact on transplant outcomes. Multicenter prospective studies are warranted to validate these findings.