Dynamics of Epstein-Barr virus on post-transplant lymphoproliferative disorders after antithymocyte globulin-conditioned allogeneic hematopoietic cell transplant.
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.
['Lindsay|Julian|J|https://orcid.org/0000-0002-7086-538X', 'Othman|Jad|J|', 'Yong|Michelle K|MK|https://orcid.org/0000-0002-8692-4145', 'Ritchie|David|D|', 'Chee|Lynette|L|', 'Tay|KimHeng|K|', 'Tio|Shio Yen|SY|', 'Kerridge|Ian|I|', 'Fay|Keith|K|', 'Stevenson|William|W|', 'Arthur|Chris|C|', 'Chen|Sharon C-A|SC|', 'Kong|David C M|DCM|https://orcid.org/0000-0002-5022-9060', 'Greenwood|Matthew|M|', 'Pergam|Steven A|SA|https://orcid.org/0000-0002-6333-5196', 'Liu|Catherine|C|', 'Slavin|Monica A|MA|https://orcid.org/0000-0002-8443-314X']
D000961:Antilymphocyte Serum D004279:DNA, Viral D020031:Epstein-Barr Virus Infections D018380:Hematopoietic Stem Cell Transplantation D004854:Herpesvirus 4, Human D006801:Humans D008232:Lymphoproliferative Disorders D012189:Retrospective Studies
antithymocyte globulin (ATG) allogeneic hematopoietic cell transplant (HCT) Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorders (PTLD)