13. PTC: Cancer Types: Blood & Lymphoma (PTLD)

Post-transplant lymphoproliferative disease, also known as PTLD, is a cancer of the white blood cells. ‘Lymphoproliferative’ means relating to proliferation (very fast growth) of lymphocytes. PTLD is a complication of anti-rejection medications and causes white blood cells to multiply out of control. There are different types of PTLD associated with transplantation, ranging from pre-cancerous diseases to more aggressive lymphomas (white blood cell cancer). PTLD can present in a single location or multiple locations, including the bone marrow, brain, digestive tract, allograft or liver. Many cases of PTLD are associated with the Epstein-Barr virus, a member of the herpes virus family. Although the Epstein-Barr virus is very common, if not treated or under control, it can cause your white blood cells to change into cancerous cells. There are four (4) main types of PTLD:

• Early lesions, which may often go away if your doctor can lower the dose of immunosuppressive drugs.
• Polymorphic PTLD, has a mix of different types of cells.
• Monomorphic PTLD, has 1 type of cell and is the most common type of PTLD.
• Other types, which are rare, such as Hodgkin’s disease.

And from the article at https://www.verywell.com/non-hodgkin-lymphoma-nhl-after-organ-transplantation-2252376
"The risk of developing lymphoma is markedly increased after solid organ transplantation for example kidney transplants, liver transplants, heart transplants or lung transplants. These lymphomas are medically termed "post-transplant lymphoproliferative disorders" or PTLDs."

 Non-Hodgkin lymphoma

Non-Hodgkin lymphoma is a type of cancer that develops in the lymphatic system, which is a network of vessels and glands spread throughout the body.  The lymphatic system is part of your immune system. A clear fluid called lymph flows through the lymphatic vessels and contains infection-fighting white blood cells known as lymphocytes.  In non-Hodgkin lymphoma, the affected lymphocytes start to multiply in an abnormal way and begin to collect in certain parts of the lymphatic system, such as the lymph nodes (glands). The affected lymphocytes lose their infection-fighting properties, making you more vulnerable to infection. The most common symptom of non-Hodgkin lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin.

Non-Hodgkin lymphoma can occur at any age, but your chances of developing the condition increase as you get older, with just over a third of cases diagnosed in people over 75. Slightly more men than women are affected.

Check out this PTLD video:

 

Note: For full versions of any of the INTRO video clips below, go to the full library of ONLINE resources at https://www.triowebptc.org/link/resource-library.html

 

What symptoms should patients be on the lookout for?

The most common symptom of PTLD is painless lumps in the neck, armpit or groin. These lumps are swollen lymph nodes where abnormal white blood cells gather. Lymph nodes are small glands that serve as filters by trapping viruses, bacteria and other causes of illnesses before they infect other parts of your body. However, lymph nodes can become larger in deeper places inside the body where you cannot feel them from the outside. You may also have more general symptoms like fever, night sweats, weight loss, fatigue, and just generally not feeling well.

These symptoms can be mistaken for other infections, transplant rejection or a reaction to the medication. If you are experiencing any symptoms, it is important to contact your transplant team right away.  Are there any visual signs? You might notice painless, swollen lymph nodes in a visible place. Like feeling a lump in your neck, armpit or groin. Lymph nodes inside of your body can be seen from imaging studies (CT scan, MRI, etc). Your transplant team can arrange these, if necessary.

How Common is Lymphoma after Organ Transplant?

PTLD includes a wide variety of lymphoproliferative conditions following solid organ or hematopoietic stem cell transplantation (HSCT) and may occur 10 percent of adults post-transplant. A range of 1 to 20 percent has also been used to estimate the overall incidence of post-transplant LPD.

Why Do Lymphomas Occur after Organ Transplant?

Post-transplant lymphomas are almost always related to infection by the Epstein Barr Virus (EBV). Infection by the Epstein Barr Virus causes a transformation of B-cells (a type of lymphocyte or white blood cell) which becomes cancerous. In normal individuals, other cells of the immune system can tackle the EBV infection, but for people with organ transplants, high doses of drugs that suppress the immune system must be administered. With nothing to control the infection, the chances of developing lymphomas increase.

What Factors Increase the Risk of Post-Transplant Lymphoma?

The two main factors that determine the chances of getting lymphoma are:

• How much immunosuppressive treatment is required – The more the immunosuppression, the more the chances of EBV infection.

• The status of EBV serology of the recipient of the transplant – If the individual has previously been infected by EBV (has a history of having had mono) the chances are that the body remembers the infection and the blood already has special proteins called antibodies that can identify and kill the virus. That can be tested by taking a blood sample.

How Do Post-Transplant Lymphomas Behave?

On average, if PTLD is going to occur, a typical time for it to do so is at about 6 months post-transplant in solid organ transplant patients and 2–3 months in HSCT recipients, but it has been reported as soon as 1 week and as late as 10 years after transplant. 

Post-transplant lymphomas are usually different from the usual Non-Hodgkin lymphomas. The cancer cells of this lymphoma are of a mixture of different shapes and sizes. While most patients have involvement mainly of lymph nodes, other organs are very commonly affected as well – a phenomenon called ‘extranodal’ involvement. These include the brain, lungs and intestines. The transplanted organ can also get involved.

How is Post-Transplant Lymphoma Treated?

 

Whenever possible, immunosuppressive treatment has to be reduced or stopped. In those who have small and localized disease, surgery or radiation may be attempted. If not, the first line of treatment is usually Rituxan (rituximab), a monoclonal antibody that specifically targets lymphoma cells. Only when this fails is chemotherapy attempted. Chemotherapy is deferred until necessary as in partially immunosuppressed individuals chemotherapy may further increase the risk of infections.
In those who develop lymphomas after bone marrow transplants, donor leukocyte transfusions can be highly effective.

What are the Outcomes with Post-Transplant Lymphomas?

In general, PTLD is a major cause of illness and death, historically with published mortality rates up to 40–70 percent in patients with solid organ transplants and 90 percent in patients post-HSCT. Non-Hodgkin lymphomas occurring after organ transplants have a poorer outcome than other NHLs. Another published figure has been that around 60-80% ultimately succumb to their lymphoma. However, the use of Rituxan has changed the survival rate, and some individuals do fare a lot better and may get cured.

The involvement of other organs, especially the brain, has a poor prognosis.
_{SourceHe, G., Wang, C., Tan, H., and S. He. Rituximab after autologous stem cell transplantation enhances survival of B-cell lymphoma patients: a meta-analysis and systematic review. Transplant Proceedings. 2015. 47(2):517-22.}

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