Retrospective evaluation of serum Epstein Barr virus DNA levels in 406 allogeneic stem cell transplant patients

Background and Objectives An HLA-mismatched donor and a T-cell-depleted graft are known risk factors for Epstein-Barr virus (EBV) reactivation after stem cell transplantation. We studied the frequency and outcome of serum EBV DNA levels in patients transplanted with an unmanipulated graft from an HLA-identical donor. Design and Methods Overall, 5479 serial serum samples from 406 consecutive allogeneic stem cell transplant recipients were analyzed retrospectively for EBV DNA with quantitative polymerase chain reaction (PCR). Results EBV DNA was found in the serum of 56 of the 406 patients (14%). EBV positivity was seen in 9% of the recipients of a graft from a sibling donor and in 29% of those with an unrelated donor. EBV-PCR positivity resolved without specific treatment in a third of the cases, in another third the copy number increased progressively or was high in the last serum sample, and in the remaining third the copy numbers were low in all positive sera including the last sample. In multivariate analysis antithymocyte globulin given for any reason and grade III-IV acute graft-versus-host disease were the only statistically significant risk factors for EBV reactivation. Only 8/56 patients with EBV-DNA positivity were alive at the time of the present analysis. The outcome of EBV-PCR positivity could not be predicted by the copy number or the timing of the first positive sample. Interpretation and Conclusions EBV reactivation was a common phenomenon in allogenic stem cell transplant recipients. In many patients the viremia resolved without EBV-directed treatment. Severe acute graft-versus-host disease and antithymocyte globulin given for any reason were risk factors for EBV viremia.