Journal of Cancer Research and Clinical Oncology

, Volume 144, Issue 8, pp 1569–1580 | Cite as

The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients

  • Neval E. WarehamEmail author
  • Amanda Mocroft
  • Henrik Sengeløv
  • Caspar Da Cunha-Bang
  • Finn Gustafsson
  • Carsten Heilmann
  • Martin Iversen
  • Nikolai S. Kirkby
  • Allan Rasmussen
  • Søren Schwartz Sørensen
  • Jens D. Lundgren
  • MATCH in PERSIMUNE study group
Original Article – Clinical Oncology



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.


Transplantation EBV DNA PTLD AUROC 


Author contributions

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.

Ethical approval

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.

Informed consent

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.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

432_2018_2674_MOESM1_ESM.docx (17 kb)
Additional Supporting Information may be found online in the supporting information tab for this article. Supporting information include definition of PTLD (Online Resource 1). (DOCX 17 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Neval E. Wareham
    • 1
    Email author
  • Amanda Mocroft
    • 2
  • Henrik Sengeløv
    • 3
  • Caspar Da Cunha-Bang
    • 3
  • Finn Gustafsson
    • 4
  • Carsten Heilmann
    • 5
  • Martin Iversen
    • 4
  • Nikolai S. Kirkby
    • 6
  • Allan Rasmussen
    • 7
  • Søren Schwartz Sørensen
    • 8
  • Jens D. Lundgren
    • 1
  • MATCH in PERSIMUNE study group
  1. 1.CHIP, Department of Infectious Diseases, Section 2100Rigshospitalet, University of CopenhagenCopenhagen ØDenmark
  2. 2.Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global healthUniversity College LondonLondonUK
  3. 3.Department of HaematologyRigshospitaletCopenhagenDenmark
  4. 4.Department of CardiologyRigshospitaletCopenhagenDenmark
  5. 5.Department of PediatricsRigshospitaletCopenhagenDenmark
  6. 6.Department of Clinical MicrobiologyRigshospitaletCopenhagenDenmark
  7. 7.Department of Surgical GastroenterologyRigshospitaletCopenhagenDenmark
  8. 8.Department of NephrologyRigshospitaletCopenhagenDenmark

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