Preemptive management of Epstein-Barr virus reactivation after hematopoietic stem-cell transplantation

Transplantation. 2009 Apr 27;87(8):1240-5. doi: 10.1097/TP.0b013e31819f1c49.


Background: Epstein-Barr virus (EBV) reactivation after hematopoietic stem-cell transplantation can lead to posttransplant lymphoproliferative disease (PTLD), which carries a high mortality rate. Among therapeutic and prophylactic options being developed, B-cell depletion with monoclonal antibodies is encouraging. Because viral load after transplantation is correlated with PTLD occurrence, we developed a preemptive attitude based on polymerase chain reaction (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 milliliter (gCop/mL) or two rising values above 10,000 gCop/mL. Weekly rituximab infusion at the dose of 375 mg/m was administered until negative PCR results were available. We evaluated the incidence of EBV reactivation and PTLD development.

Results: Nineteen 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 three 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 feasible but probably overtreated patients. Prospective trials are strongly needed, they should use uniform PCR techniques and consider higher threshold values for treatment initiation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Aplastic / therapy
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • DNA, Viral / genetics
  • Epstein-Barr Virus Infections / drug therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Leukemia / therapy
  • Lymphoma / therapy
  • Middle Aged
  • Myelodysplastic Syndromes / surgery
  • Polymerase Chain Reaction
  • Rituximab
  • Survival Analysis
  • Survivors
  • Virus Activation / drug effects*
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • DNA, Viral
  • Immunologic Factors
  • Rituximab