EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era

Bone Marrow Transplant. 2014 Feb;49(2):280-6. doi: 10.1038/bmt.2013.170. Epub 2013 Nov 11.


EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50-65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had 10 000 and 40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12-0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / pharmacology
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cohort Studies
  • Epstein-Barr Virus Infections / drug therapy
  • Epstein-Barr Virus Infections / etiology*
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunotherapy
  • Lymphoproliferative Disorders / virology*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Rituximab
  • Survival Analysis
  • Transplantation Conditioning / adverse effects*
  • Transplantation Conditioning / methods
  • Viral Load


  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Rituximab