Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

Clin Infect Dis. 2013 Sep;57(6):794-802. doi: 10.1093/cid/cit391. Epub 2013 Jun 13.


Background: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.

Methods: A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease.

Results: One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival.

Conclusions: More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.

Keywords: Epstein-Barr virus; hematopoietic stem cell transplantation; post-transplant lymphoproliferative disorder; prognostic model; risk factors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Child
  • Child, Preschool
  • DNA, Viral / blood
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / surgery
  • Epstein-Barr Virus Infections / virology
  • Europe / epidemiology
  • Hematopoietic Stem Cell Transplantation*
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunologic Factors / therapeutic use*
  • Infant
  • Kaplan-Meier Estimate
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / epidemiology
  • Lymphoproliferative Disorders / surgery
  • Lymphoproliferative Disorders / virology
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Viral Load


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