Understanding EBV+ PTLD
What is EBV+ PTLD?
Epstein–Barr virus (EBV)-positive
post-transplant lymphoproliferative
disorder (PTLD) – or EBV+ PTLD – is a
serious complication that can occur
following solid organ transplant (SOT)
or haematopoietic cell transplant (HCT).1,2
It develops when T-cell control of EBV infection or reactivation of latent infection is lost, allowing EBV-infected B cells to proliferate uncontrollably.1,2,4
Although EBV+ PTLD can be aggressive and
life-threatening,1,3 growing understanding
of its biology and treatment pathways is
helping physicians manage this complex
condition with greater clarity and confidence.
EBV, a y-herpes virus, is present in
≥90% of adults4
EBV persists as a lifelong latent infection within memory B cells in most people1,4
EBV+ PTLD can be aggressive, life-threatening, and remains a challenging disease to manage2,5,6
How EBV+ PTLD develops
EBV infection early in life can remain hidden, and in transplant patients the loss
of immune control may allow it to progress into EBV+ PTLD.3,7
01 Primary infection
EBV typically establishes infection early
in life by invading host B cells3
Simplifed model for illustrative purposes only.
02 Latency
Cytotoxic T cells normally recognise and
clear EBV-infected B cells, but some escape
detection, creating latent infection3,7
03 Loss of immune control
In immunocompromised patients, such as
transplant recipients, EBV cannot be
controlled efficiently, allowing uncontrolled
proliferation of infected B cells and
the development of EBV+ PTLD3,7
Role of immunosuppression
Although the type of immunosuppression differs between SOT and HCT,
both settings can impair T-cell control, enabling EBV-infected B cells to expand
and contribute to the development of PTLD.
|
Solid organ transplant (SOT) |
Haematopoietic cell transplant (HCT) |
|---|---|
|
Immunosuppression to prevent allograft rejection2 Induction therapy is given during the peri-transplant period Maintenance therapy begins at transplantation and continues |
Immunosuppression1 Conditioning regimens given before donor stem cell infusion Immunosuppressive agents administered post-transplant |
|
EBV infection1,2 EBV-infected B cells proliferate due to impaired T-cell immunity Extended B-cell lifespan allows for genetic aberrations |
|
|
Reduced T-cell surveillance is a key driver |
T-cell dysfunction combined with cytokine-driven |
|
Typical cell of origin: |
Typical cell of origin: |
Rates of EBV+ PTLD after transplant
After SOT
1st year post-transplant risk is highest1,8
7–10 years later a second peak occurs8
4–5.3 years median time to PTLD onset,
due to taking lifelong immunosuppressives1
After HCT
EBV+ PTLD usually occurs within 12 months1
Only 4% of cases develop after 1 year10
2–4 months median time to PTLD onset10
PTLD cases >5 years post-HCT are extremely rare as immunosuppression is usually discontinued1
*After SOT, incidence of PTLD varies by organ type, pre-transplant EBV antibody status, and patient age;3 after HCT, incidence varies by patient factors, stem cell source, HLA mismatch, and conditioning regimen.1
Rate of EBV+ PTLD after HCT
Rate of EBV+ PTLD
after HCT
In a multicentre retrospective study of 127 patients with PTLD following allogeneic HCT, incidence peaked 2–3 months after transplantation and declined sharply thereafter11
Adapted from Landgren O, et al. Blood. 2009.
Time to PTLD after SOT
Median time to diagnosis of PTLD by organ type:12*
Time to PTLD
after SOT
(by organ)
A single-centre retrospective study found that PTLD developed later after heart transplantation compared with other SOTs, consistent with findings reported elsewhere12
*Out of 66 patients identified with a histologically confirmed diagnosis of PTLD, 50 were EBV+, 10 were unknown, and 6 were EBV-negative.
