Dynamics of Epstein-Barr virus on post-transplant lymphoproliferative disorders after antithymocyte globulin-conditioned allogeneic hematopoietic cell transplant

Transpl Infect Dis. 2021 Oct;23(5):e13719. doi: 10.1111/tid.13719. Epub 2021 Sep 12.


Background: The use of antithymocyte globulin (ATG) in allogeneic hematopoietic cell transplant (HCT) is associated with an increased risk of Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD). The dynamics and outcomes of EBV-DNAemia are not well described in this population.

Methods: We retrospectively assessed the kinetics of EBV-DNAemia after ATG conditioning of HCT recipients. Receiver operating characteristic (ROC) curves were used to assess EBV-DNAemia to predict EBV-PTLD in this group.

Results: A total of 174/405 (43%) consecutive HCT recipients from two centers met inclusion criteria of ATG conditioned, non-B-cell lymphoma patients. Of these with EBV-DNA measured using standardized IU/ml, 78.6% (92/117) developed EBV-DNAemia: 62% spontaneously resolved; 19% cleared after preemptive rituximab, and 13% developed EBV-PTLD. ROC curve analysis using maximum pre-EBV-PTLD EBV-DNAemia, demonstrated an AUC of 0.912 with EBV-DNAemia of 9782 IU/ml, associated with 82.6% sensitivity and 94.4% specificity for development of EBV-PTLD. Median time for EBV-DNAemia to increase from initial detection to >1000 IU/ml was 7 days; to >10 000 IU/ml, 12 days; and to >100 000 IU/ml, 18 days. Median EBV-DNAemia level prior to administration of rituximab was significantly lower in patients with successful preemptive treatment, compared with those who developed EBV-PTLD (3.41 log10 IU/ml [3.30-3.67] vs. 4.34 log10 IU/ml [3.85-5.13], p = .002; i.e., 2628 IU/ml vs. 21 965 IU/ml, respectively).

Conclusions: EBV-DNAemia >10 000 IU/ml was the strongest predictor of the development of EBV-PTLD, and progression to this level was rapid in ATG-conditioned HCT recipients. This information may guide EBV-PTLD management strategies in these high-risk patients.

Keywords: Epstein-Barr virus (EBV); allogeneic hematopoietic cell transplant (HCT); antithymocyte globulin (ATG); post-transplant lymphoproliferative disorders (PTLD).

MeSH terms

  • Antilymphocyte Serum / therapeutic use
  • DNA, Viral
  • Epstein-Barr Virus Infections* / drug therapy
  • Epstein-Barr Virus Infections* / epidemiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Herpesvirus 4, Human / genetics
  • Humans
  • Lymphoproliferative Disorders* / drug therapy
  • Lymphoproliferative Disorders* / etiology
  • Retrospective Studies


  • Antilymphocyte Serum
  • DNA, Viral