Preemptive Management of Epstein-Barr Virus Reactivation after Hematopoietic Stem Cell Transplantation.

Introduction - Epstein-Barr virus (EBV) reactivation after hematopoietic stem cell transplantation can lead to posttransplant lymphoproliferative disease (PTLD), which carries a high mortality rate. Transplants using T-cell-depleted graft or antithymocyte globulin are considered as high-risk. Among therapeutic and prophylactic options being developed, B-cell depletion with monoclonal antibodies is encouraging. Since viral load after transplantation is correlated to PTLD occurrence, we have developed a preemptive attitude based on PCR-guided rituximab administration.

Methods - We monitored 115 transplant patients with a quantitative PCR for EBV DNA performed on whole-blood samples. Criteria for treatment initiation were a single PCR above 40,000 DNA genome copies per litre (gCop/L) or two rising values above 10,000 gCop/L. Weekly rituximab infusion at the dose of 375 mg/m² was administered until negative PCR results were available. We evaluated incidence of EBV reactivation and PTLD development.

Results - 19 patients (16.5%) met the criteria for treatment. Incidence of reactivation was the same in high-risk and standard-risk patients (12 vs 7, p=0.38). One patient developed PTLD after discontinuation of therapy due to a serious adverse event. No other serious adverse events were noticed. Viral load disappeared after a median of 3 cycles of therapy and weekly monitoring allowed prompt intervention. No PTLD-related death was observed, all-cause mortality in the treated population was 68%.

Conclusions - Our PCR-guided and rituximab-based preemptive approach to avoid PTLD after allogeneic hematopoietic stem cell transplantation is safe and feasible but probably overtreated patients. Prospective trials should concentrate on high-risk patients, use uniform PCR techniques, and consider higher threshold values for treatment initiation.