The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients
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Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT).
We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD.
EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8–20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64–79%) among SOT and 59% (51–68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75–90%) among SOT and 84% (79–89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78–91%).
We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.
KeywordsTransplantation EBV DNA PTLD AUROC
NEW designed the study, assisted in data collection and analysis, and drafted and edited the manuscript. JDL designed the study, assisted in data collection and analysis, and edited the manuscript. AM designed the study, performed data analysis and edited the manuscript. CDB, NK, FG, MI, AR, HS, SSS, and CH assisted in data collection and edited the manuscript.
This work was supported by Danish National Research Foundation [Grant number 126].
Compliance with ethical standards
Conflict of interest
NEW declares that she has no conflict of interest. AM declares that she has no conflict of interest. CDB declares that he has no conflict of interest. NK declares that he has no conflict of interest. FG declares that he has no conflict of interest. CH declares that he has no conflict of interest. MI declares that he has no conflict of interest. AR declares that he has no conflict of interest. HS declares that he has no conflict of interest. SSS declares that he has no conflict of interest. JDL declares that he has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
All relevant approval for this project was obtained from the Danish Health and Medicines Authorities according to Danish legislation on retrospective studies. For this type of study, formal consent is not required.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
- Fox CP, Burns D, Parker AN et al (2014) 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 49(2):280–286CrossRefPubMedGoogle Scholar
- Meijer E, Slaper-Cortenbach IC, Thijsen SF, Dekker AW, Verdonck LF (2002) Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique. Bone Marrow Transplant 29(4):335–339CrossRefPubMedGoogle Scholar
- San-Juan R, Manuel O, Hirsch HH et al (2015) Current preventive strategies and management of Epstein–Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based cross-sectional survey. Clin Microbiol Infect 21(6):604–609CrossRefPubMedGoogle Scholar
- Styczynski J, Gil L, Tridello G et al (2013) 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 57(6):794–802CrossRefPubMedGoogle Scholar