We monitored 133 high-risk allo-SCT recipients for 6 months after transplant for EBV reactivation by quantitative real-time PCR. Rituximab was given as pre-emptive therapy for viremia 41000 copies/mL. The 1-year cumulative incidence of EBV reactivation was 29.4% (95% confidence interval (CI): 18-40) in patients monitored due to initial high-risk characteristics (n = 93) and 31.8% (95% CI: 19.7-44) in those followed because of the development of refractory GVHD (n = 40). Overall response rate to Rituximab was 83%. Nine patients (9.6%) developed post-transplant lymphoproliferative disorder (PTLD) at a median of +62 days after SCT. Eight of them showed a concomitant CMV reactivation. Second SCT was the only risk factor associated with EBV infection and PTLD in multivariate analysis (hazard ratio (HR) 2.6 (95% CI: 1.1-6.4; P = 0.04) and HR 6.4 (95%CI: 1.3-32; P = 0.02)). The development of EBV reactivation was not associated with non-relapse mortality or OS (P = 0.97 and P = 0.84, respectively).Bone Marrow Transplantation (2015) 50, 579-584; doi:10.1038/bmt.2014.298; published online 12 January 2015 INTRODUCTION Epstein-Barr virus-related post-transplant lymphoproliferative disorder (PTLD) is a serious complication after SCT with a mortality as high as 85%. 1 Major risk factors for PTLD include HLA disparity, graft T-cell depletion and administration of anti-thymocyte globulin (ATG) or other anti T-cell antibodies. 2,3 PTLD is usually preceded by a preclinical phase characterized by rising EBV copies in peripheral blood which can be quantified by polymerase-chain reaction (PCR). Recent guidelines recommend monitoring EBV viral load in high-risk allo-SCT recipients, according to the mentioned predisposing factors. 4 The real incidence and prognosis of EBV disease are difficult to evaluate due to differences in the PCR methods used to test EBV DNA, the quantitative PCR thresholds for therapeutic intervention and the diversity of criteria for defining high-risk patients. 5 Efforts to improve immune responses by reducing immunosuppressive drugs remain as one of the cornerstones of management but are not applicable to patients with active GVHD; 6,7 thus, eliminating B lymphocytes with the anti-CD20 monoclonal ab Rituximab is the most feasible treatment. 7 In the current study we compare the incidence and prognosis of EBV-related complications between patients with baseline highrisk characteristics for PTLD and patients affected by refractory GVHD, prospectively monitored for EBV DNAemia with early institution of Rituximab as pre-emptive therapy.