The etiology of EBV+ PTLD

A common virus that can result in a hematologic malignancy post-transplant

Sometimes called post-transplant lymphoma, EBV+ PTLD is a hematologic malignancy triggered by EBV-infected B-cell proliferation in patients with suppressed and/or depleted T cells.

  • Over 90% of the general population is EBV-positive, with 95% EBV-positive by age 40 in the developed world1,2
  • EBV-infected individuals with healthy immune systems harbor small reservoirs of latently infected B cells; however, they do not exhibit any clinical symptoms1
  • T-cell suppression and/or depletion from transplant immunosuppression can impair immune response3
  • When cytotoxic T-cell response is impaired, uncontrolled proliferation of EBV-infected B cells may occur, leading to immunosuppression-associated lymphoproliferative disorders (IA-LPDs) such as EBV+ PTLD3,4
EBV cells

EBV cells

Reported incidence

EBV+ PTLD is an unpredictable threat for post-transplant patients

The incidence of EBV+ PTLD varies depending on a couple of factors. With this in mind, it is important to consider not only which type of transplant the patient received but also the immunosuppression regimen used.

Additionally, whether or not the patient has preexisting immunity to EBV may increase the probability of EBV+ PTLD occurring. Because incidence rates can vary, they are correlated with the number of risk factors.1

Incidence may also be impacted by the following5,6:

  • Growing number of transplantations
  • Older age of donors and recipients
  • Use of new immunosuppressive agents and regimens
  • Type of donor or donation
  • Increased awareness of the disease
  • Improved diagnostic tools
Woman looking in the distance

Risk factors for EBV+ PTLD

T-cell suppression plays a major role

Impaired immune function due to T-cell suppression and/or depletion is a primary cause of EBV+ PTLD.1,7

In allogeneic HCT patients

  • Risk rates are affected by immunosuppressive regimen used and type of donor or donation, including mismatched family donor, matched unrelated donor, mismatched unrelated donor, and cord blood transplant6
  • Other factors include age >50 years, underlying disorder, and prior splenectomy5

In SOT patients

  • The intensity of induction immunosuppressive therapy and duration of therapy as well as organ type affect risk rates5
  • Other factors that affect risk include EBV mismatch at the time of transplantation, underlying disorder, race or ethnic group, and older donor age or younger recipient age5
  • Furthermore, at the time of transplant, EBV-seronegative patients have an 8-fold increased risk of developing PTLD versus patients who are EBV-seropositive.9

Risk per organ type8

Icons of different transplant organs with their respective EBV+ PTLD risk factor percentage
Intestinal and multi-organ

Icons of different transplant organs with their respective EBV+ PTLD risk factor percentage

Icons of different transplant organs with their respective EBV+ PTLD risk factor percentage

Icons of different transplant organs with their respective EBV+ PTLD risk factor percentage

Icons of different transplant organs with their respective EBV+ PTLD risk factor percentage


1. Martinez OM, Krams SM. The immune response to Epstein Barr virus and implications for posttransplant lymphoproliferative disorder. Transplantation. 2017;101:2009-2016. 2. Auwaerter P. Epstein-Barr virus. Johns Hopkins Medicine POC-IT Guides website. Updated May 29, 2016. Accessed September 21, 2018. 3. Glotz D, Chapman JR, Dharnidharka VR, et al. The Seville expert workshop for progress in posttransplant lymphoproliferative disorders. Transplantation. 2012;94:784-793. 4. Natkunam Y, Gratzinger D, Chadburn A, et al. Immunodeficiency-associated lymphoproliferative disorders: time for reappraisal [published online ahead of print August 6, 2018]? Blood. doi:10.1182/blood-2018-04-842559. 5. Dierickx D, Habermann TM. Post-transplantation lymphoproliferative disorders in adults. N Engl J Med. 2018;378:549-562. 6. Styczynski J, Giebel S. Post transplant lymphoproliferative syndromes. In: Carreras E, Dufour C, Mohty M, Krögen N, eds. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. 7th ed. Cham, Switzerland: Springer; 2019:347-352. 7. Fox CP, Burns D, Parker AN, et al. 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;49:280-286. 8. Dharnidharka VR, Webster AC, Martinez OM, et al. Post-transplant lymphoproliferative disorders. Nat Rev Dis Primers. 2016;2:15088. 9. Peters AC, Akinwumi MS, Cervera C, et al. The changing epidemiology of posttransplant lymphoproliferative disorder in adult solid organ transplant recipients over 30 years: a single-center experience. Transplantation. 2018;102:1553-1562.