Post-Transplant Lymphoproliferative Disorder (PTLD)

What is Post-Transplant Lymphoproliferative Disorder (PTLD)?

Post-transplant lymphoproliferative disorder (PTLD) is a group of certain lymphomas that can happen in children and adults after:

• A solid organ transplant (kidney, lung, heart, liver). PTLD often happens 30-40 months after a solid organ transplant.
• An allogeneic bone marrow (stem cell) transplant (when the cells come from a donor). PTLD often happens within 6 months of a stem cell transplant.

PTLD is rare but is one of the most common cancers that can happen after a transplant.

What causes PTLD?

PTLD is caused by a quick rise in lymphoid (immune) cells that can happen after a transplant. In most cases, PTLD is thought to be caused by the Epstein-Barr virus (EBV) that infects B-cells, part of your immune system. EBV is a type of herpes virus that most (90% or more) adults have already been infected with. Most people do not know they have had EBV. It stays in your body but is kept in check by your immune system. It does not cause long-term health problems when it is “dormant,” or not active.

For a transplant to work, you need medications called immunosuppressants that suppress (lower) your immune system. These medications are given at the time of your transplant, and you will likely need to take them for the rest of your life.  They help your body accept the new organ or cells and can prevent rejection (when your body fights back against the new organ or cells). When taking immunosuppressants, your immune system cannot stop EBV from growing out of control. The virus may be reactivated, or you may have a new EBV exposure.

PTLD after bone marrow transplant is thought to be caused by the removal of T cells, which is often part of the transplant to help lower the chance of rejection.

Types of PTLD

According to the World Health Organization (WHO), there are 5 main types of PTLD: 

• Plasmacytic hyperplasia and infectious mononucleosis-like PTLD: These are early PTLD lesions.
• Florid follicular hyperplasia: These are early PTLD lesions.
• Polymorphic PTLD: There is a mix of too many B- and T-cells. Lymphoma cells are mixed in with normal, healthy cells in the body.
• Monomorphic PTLD: The cells and how they act fall into a recognized type of lymphoma, most commonly as non-Hodgkin's lymphoma of B-cell origin and, rarely, T-cell lymphoma.
• Classic Hodgkin lymphoma-like PTLD: The lymphoma cells look like Reed-Sternberg cells, which are a sign of classic Hodgkin lymphoma.

Symptoms of PTLD

Symptoms of PTLD may be:

• Painless, swollen lymph nodes.
• Fever.
• Night sweats.
• Weight loss.
• Fatigue.
• General discomfort.

It is important to talk to your transplant team right away about any new symptoms. If they think you may have PTLD, you will likely need a biopsy. You may also need other scans and blood tests to find which type of PTLD you have.

Treatment of PTLD

At this time, there are no treatments approved by the Food and Drug Administration (FDA) for PTLD. The goal of treatment is to cure PTLD while keeping the transplanted organ or cells working.

The most common treatments for PTLD are:

• Lowering the amount of the immunosuppressive medications you are taking. This is mostly used in early PTLD lesion types (plasmacytic hyperplasia and infectious mononucleosis-like PTLD).
• Rituxan (rituximab).
• Chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisone) in combination with rituximab (called R-CHOP) or T cell immunotherapy medications.
• Surgery or radiation therapy.

Antiviral medications, like ganciclovir and acyclovir, may be used to prevent EBV-related PTLD, but they cannot treat PTLD.

There are new therapies, like immunotherapy and targeted therapy, that are being studied in clinical trials. Talk with your care team about your risk of developing PTLD if you are going to have a solid organ or stem cell transplant, or if you have any questions about symptoms of PTLD.

Resources for More Information

NORD PTLD: https://rarediseases.org/rare-diseases/posttransplant-lymphoproliferative-disorders/

Leukemia and Lymphoma Society PTLD Factsheet http://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS33_PTLD_2018_FINAL.pdf