World Lymphoma Awareness Day –Understanding Post-Transplant Lymphoproliferative Disorders (PTLD)

Understanding PTLD 

Post-Transplant Lymphoproliferative Disorder (PTLD) is a spectrum of lymphoid proliferations that can occur following hematopoietic (bone marrow) or solid organ transplantation^3,4. Patients who receive a transplant are subjected to a strong immunosuppressive regimen to prevent rejection, which makes individuals susceptible to the disease, resulting in very few cases of PTLD⁵.

PTLD is characterized by proliferation of white blood cells (B lymphocytes) which often are infected by the Epstein Barr virus⁶.

What is PTLD? 

Post-Transplant Lymphoproliferative Disease or Disorder

‘Lympho’ refers to lymphocytes, a type of white blood cell 'Proliferative’ means growing or multiplying quickly.

PTLD is one of the rare but serious complications that can happen after a transplant. PTLDs can range from mild, benigngrowths to aggressive cancers. In PTLD, your lymphocytes grow out of control after a transplant. Lymphocytes are part of the immune system. In most cases, the lymphocytes affected are the B cells.

PTLD is often linked to the Epstein-Barr virus (EBV).

If there is no link, it’s called EBV‑negative PTLD. If there is a link, it’s called EBV‑positive PTLD. EBV is a common virus that infects B cells in the body. The infection can cause some B cells to multiply abnormally.

What causes PTLD?

• Although children who are infected with Epstein Barr Virus (EBV), also called infectious mononucleosis, may not display any symptoms, the virus can lead to the development of mononucleosis in adolescents and adults.⁷
• It is estimated that 90% of the world-wide adult population has life-long EBV infection.⁷
• Immunosuppressive therapy can produce the reactivation of EBV-infected B lymphocytes.^8,9
• In an immunosuppressed patient, T-cells are low in number, and they cannot properly eliminate the virus.¹⁰ This can lead to the rapid proliferation of EBV-infected B-cells, causing PTLD.⁶

Prevalence and Risk of PTLD

PTLD occurs in solid organ transplants and in hematopoietic stem cell transplantation^3,4.

Who is at risk for PTLD?

Anyone who is taking immunosuppressants after a transplant is at risk for PTLD. Immunosuppressants must be taken after a:

• solid organ transplant to prevent transplant rejection
• blood stem cell transplant from a donor to prevent graft-versus-host disease (GvHD).

Immunosuppressants protect the transplant by weakening the immune system.

Normally, the immune system protects the body against foreign and harmful things. Harmful things may include viruses, bacteria, and cells that have become abnormal. After a transplant, a person’s immune system is weakened. This can increase the risk of PTLD. Patients should not stop taking immunosuppressants. They should talk to their transplant doctor about any questions or concerns.

The risk of developing PTLD depends on the degree of immunosuppression, the EBV serostatus and age.^8,9,13,14

• The more immunosuppressed the patient is, the greater the risk of developing PTLD.^12,14 The degree of compatibility between recipient and donor is very important, especially in the case of stem cell transplants.^12,14
• PTLD can occur when the transplanted patient’s own EBV is reactivated or because the EBV from the donor is reactivated in the patient.^8,9
• Children under 10 years and adults over 50 years (haematopoietic transplant) or 60 years (solid organ transplant) are at higher risk of developing PTLD.^12,14

Symptomatology and diagnosis

Some of the common PTLD symptoms are: ^8,9,14

What are the symptoms?

The symptoms of PTLD are broad. They can overlap with symptoms of other conditions. Symptoms can be different in different people, and may include:

• a general change in how the patient is feeling
• swollen lymph nodes
• unexplained weight loss over a few weeks
• fever or night sweats
• sore throat
• fatigue
• chronic sinus congestion
• severe abdominal pain
• no appetite, nausea, or vomiting
• black or bloody stools

These symptoms are not unique to PTLD and are similar to the symptomatology associated with organ rejection that can occur after undergoing a transplant.^8,14

Different methods are used to establish a diagnosis of PTLD: ^9,15

How is PTLD diagnosed?

The transplant team will review the patient’s medical and transplant history. Patients may also have to meet other healthcare providers and go in for:

	Biopsies (to take tissue samples) e.g., blood, bone marrow, cerebral spinal fluid, etc.
	Medical imaging e.g., CT scan, PET scan, MRI, etc.

The transplant team will test the tissue samples and look at the results. Two important tests are levels of EBV and how immune cells in the patient’s body may have changed.

Treatment options

There are different treatments options:

	Adjusting the immunosuppressants helps the immune system control PTLD while keeping the transplant healthy.
	Antibody therapy helps the immune system recognize and fight specific cells. In PTLD, it may be used to target B cells.
	CAR T-cell therapy is made from the patient’s T cells. The patient’s T cells are genetically modified in the lab to attack specific types of cancer cells.
	Chemotherapy  kills cells that grow and multiply quickly, including cancer cells. When it is used with antibody therapy, it’s called chemoimmunotherapy.
	Surgery and Radiotherapy  are not usually used to treat PTLD. They may be used to control or reduce symptoms.
	EBV-directed therapy targets and kills cells that are infected by EBV. It is used to treat diseases linked to EBV, including EBV-positive PTLD.

Reduction of the immunosuppression regimen is the main strategy in early stage PTLD^12,14,16,17. 

When reduction of the immunosuppression regimen is not feasible or ineffective antibody therapy can be used, and some patients may benefit from the addition of chemotherapy^17-20.

Living with PLTD

Living with PTLD can be a complex journey that affects not only the physical health of patients but also their emotional and psychological well-being. At Pierre Fabre Laboratories we understand that each patient's experience is unique, and we are committed to providing comprehensive support to help manage the challenges that come with this condition.

Discover our website to help patients and their families to understand the disease, find support and resources. This website is developed for people facing PTLD with the support of patient representatives. 

Understanding post-Transplant Lymphoproliferative disease.

•    Know more about what is PTLD. •    Find PTLD patient group support organisation •    in your country using an interactive map. •    Explore tools and resources to help understand PTLD

Discover more about PTLD

Our A Bright Journey campaign

Throughout 2025 and during this World Lymphoma Awareness Month, the Pierre Fabre Group wants to raise awareness about this rare condition and share more information about this disease, to offer better support to those affected by it and trying to improve their quality of life. 

Show your support to the #ABrightJourney movement this day by liking, sharing and commenting on our posts.

References

1. [Internet]. [cited 2024 Aug 26]. Available from: https://www.lymphoma.org.au/lymphoma-types/
2. [Internet]. [cited 2024 Aug 26]. Available from: https://lymphomacoalition.org/wp-content/uploads/WLAD-2023-Infographic-Signs-and-Symptoms.pdf
3. Engels EA, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA [Internet]. 2011;306(17):1891–901.
4. Kinch A, et al. A population-based study of 135 lymphomas after solid organ transplantation: The role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival. Acta Oncol [Internet]. 2014;53(5):669–79. A
5. Samant H, Vaitla P, Kothadia JP. Post-Transplant Lymphoproliferative Disorders. [Updated 2023 Feb 12]. In: Stat Pearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.
6. Martinez OM, Krams SM. The immune response to Epstein Barr virus and implications for posttransplant lymphoproliferative disorder. Transplantation [Internet]. 2017;101(9):2009–16.
7. Cohen JI. Epstein-Barr virus infection. N Engl J Med [Internet]. 2000;343(7):481–92.
8. Loren AW, Porter DL, Stadtmauer EA, Tsai DE. Post-transplant lymphoproliferative disorder: a review. Bone Marrow Transplant [Internet]. 2003;31(3):145–55.
9. DeStefano CB, et al. Management of post-transplant lymphoproliferative disorders. Br J Haematol [Internet]. 2018;182(3):330–43.
10. Ligeti K, Müller LP, Müller-Tidow C, Weber T. Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach. Transpl Res Risk Manag [Internet]. 2017;9:1–14..
11. Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94(7):2208–16.
12. Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, et al. 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 [Internet]. 2013;57(6):794–802.
13. Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep [Internet]. 2013;8(3):173–83.
14. Gulley ML, Tang W. Using Epstein-Barr viral load assays to diagnose, monitor, and prevent posttransplant lymphoproliferative disorder. Clin Microbiol Rev [Internet]. 2010;23(2):350–66. Available from: http://dx.doi.org/10.1128/CMR.00006-09.
15. Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica [Internet]. 2016;101(7):803–11.
16. Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet [Internet]. 1984;1(8377):583–7.
17. Roschewski M, Wilson WH. EBV-associated lymphomas in adults. Best Pract Res Clin Haematol [Internet]. 2012;25(1):75–89.
18. Oertel SHK, Verschuuren E, Reinke P, Zeidler K, Papp-Váry M, Babel N, et al. Effect of anti-cd 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD). American Journal of Transplantation. 2005;5(12):2901–6.
19. Choquet S. Efficacy and safety of Rituximab in B-cell post-transplantation lymphoproliferative disorders: Results of a prospective Multicenter Phase 2 study. Blood. 2006;107(8):3053–7.

20. Choquet S, Oertel S, LeBlond V, Riess H, Varoqueaux N, Dörken B, et al. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ

    transplantation: Proceed with caution. Annals of Hematology. 2007;86(8):599–607. 

HQ--08-24-2400039