Post-Transplant Lymphoproliferative Disorders (PTLD)

What are post-transplant lymphoproliferative disorders?

Post-transplant lymphoproliferative disorders (PTLD) are rare, life-threatening complications of solid organ transplants or allogeneic (donated) stem cell transplantation. Lymphoproliferative disorders are diseases that happen when white blood cells multiply uncontrollably.

PTLDs are lymphomas. Lymphomas are cancers of your lymphatic system that happen when white blood cells (lymphocytes) change into rapidly growing cancer cells that don’t die.

The disorders typically affect people who have Epstein-Barr virus (EBV). There are different PTLD types that may affect people in different ways. Healthcare providers can treat PTLD, but the condition can come back.

What are the different types of PTLD?

There are four main types of PTLD based on how lymphoma cells appear when viewed under a microscope:

• Early lesion: People with early lesion PTLD may have symptoms similar to Epstein-Barr virus (EBV).
• Polymorphic PTLD: There are lymphoma cells mixed in with cells such as normal lymphocytes, plasma cells or other types of white blood cells.
• Monomorphic PTLD: This is the most common form of post-transplant lymphoproliferative disorder. Lymphoma cells will look like cells found in non-Hodgkin lymphomas such as large diffuse B-cell lymphoma or Burkitt lymphoma.
• Classic Hodgkin lymphoma — PTLD type: This is the least common form of post-transplant lymphoproliferative disorder.

How common is post-transplant lymphoproliferative disorder?

PTLD is rare. About 2% of people who receive donor stem cells develop PTLD. People who have organ transplants are more likely to develop PTLD, but the exact incidence depends on the kind of transplant. For example, experts estimate 3% of people who have kidney transplants develop PTLD while 10% of people who have lung transplants develop the condition.

What are PTLD symptoms?

Some people don’t have symptoms right away. PTLD symptoms can appear anytime from a few months after a transplant to several years later. When they do, symptoms may include:

• Fatigue.
• Fever.
• Lack of appetite.
• Unexpected weight loss.
• Night sweats.
• Swollen lymph nodes.

What causes post-transplant lymphoproliferative disorders?

PTLD happens when a very common virus takes advantage of your immune system. If you have a stem cell transplant, you have intensive chemotherapy before your transplant to remove cancerous cells from your bone marrow.

This is conditioning, and it affects your immune system’s ability to protect you from infection. Pre-transplant conditioning for stem cell transplants affects T-cells that normally prevent B-cells infected with EBV from reactivating and multiplying.

After stem cell or organ transplant, you receive immunosuppressant medication that prevents your immune system from attacking your new organ or stem cells. But while your new organ or stem cells are protected, intruders like viruses may take advantage of your weakened immune system.

In PTLD, the viral culprit is Epstein-Barr virus (EBV). It’s linked to PTLD that happens within one to three years after a stem cell or organ transplant. Experts haven’t established a cause for PTLD that happens many years after transplant. They’re investigating whether viruses such as cytomegalovirus (CMV) or adenovirus may play a role in late PTLD.

Experts estimate nearly 90% of all people carry the virus because they were infected with EBV during childhood or adolescence. You can have EBV without having symptoms, so you may not realize you’re carrying the virus. EBV infects your B-cells so the virus stays in your body. It’s latent, meaning it’s not active and doesn’t cause issues. (You may also be infected with EBV if your donor carries the virus.)

Because you’re taking immunosuppressants, your immune system can’t keep EBV from becoming active. When this happens, your EBV-infected B-cells start multiplying, leading to PTLD.

What are PTLD risk factors?

You have an increased risk of developing PTLD if:

• You have Epstein-Barr virus because your donor has or you have the virus.
• You had pre-transplant conditioning that suppresses the normal function of your T-cells.
• You’re taking immunosuppressant medication to prevent your body from rejecting your new organ or stem cells.
• You have variations in certain genes that increase your risk of developing post-transplant lymphoproliferative disorder.

How do healthcare providers diagnose PTLD?

Providers will do a thorough physical examination and medical history. They typically do the following tests:

• Complete blood count (CBC).
• Comprehensive metabolic panel.
• Lactate dehydrogenase (LDH).
• Urinalysis, including uric acid levels.
• EBV viral antibody test to detect antibodies that cause EBV.
• Computed tomography (CT) scan.
• Magnetic resonance imaging (MRI).
• Positron emission tomography (PET) scan.
• Bone marrow biopsy.

How do healthcare providers treat PTLD?

First, they typically reduce immunosuppressant medication as much as possible. Other treatments may include:

• Chemotherapy.
• Radiation therapy.
• Immunotherapy with monoclonal antibodies.
• Surgery. In very rare situations, healthcare providers may recommend surgery if PTLD is limited to specific areas or organs and can be safely removed. For example, if PTLD affects your tonsils, providers may consider removing your tonsils.

Are there ways to prevent PTLD?

While you can’t do anything to prevent PTLD, healthcare providers and medical researchers are evaluating ways to use certain medications before and/or after transplant to reduce PTLD risk.

What can I expect if I have post-transplant lymphoproliferative disorder?

Your prognosis or expected outcome will vary based on your situation. For example, sometimes, PTLD goes away when healthcare providers reduce immunosuppressant medications. For another example, recent studies show about 60% to 70% of people who developed lymphoma after an organ transplant went into remission (decreased or no signs of cancer) following treatment that combined immunotherapy and chemotherapy for lymphoma.

Is there a cure for PTLD?

Yes, immunotherapy alone or in combination with chemotherapy can cure PTLD. Studies show about 50% to 60% of people with PTLD are cured after receiving these treatments.

What questions should I ask my healthcare provider?

If you have PTLD, you may want to ask your provider some of the following questions:

• Why did I develop this condition?
• How do you treat PTLD?
• If you reduce my immunosuppressant medication, what are the chances my body will reject my new organ or stem cells?
• If my treatment is successful, what are the chances the condition will come back?

When should I see my healthcare provider?

If you have PTLD, your provider will carefully monitor your overall health for signs your condition is getting worse. If you’re receiving treatment for PTLD, your provider will explain what changes in your body or symptoms may be signs of increasing issues.

A note from Cleveland Clinic

If you need an organ or stem cell transplant, receiving new organs or donated stem cells may save your life or help you live longer. But transplants are major medical procedures that come with certain risks. A post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication of stem cell and organ transplant.

PTLD is one of many risk factors you and your healthcare team will discuss if you’re a candidate for a stem cell or organ transplant. Healthcare providers and medical researchers are evaluating ways to reduce the risk of PTLD. If you’re a candidate for organ or stem cell transplantation, your healthcare team will be glad to answer your questions about PTLD risk.