Post-Transplant Lymphomas

Incidence and treatment of post-transplant non-hodgkin's lymphoma

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.

Doctor with X-ray talking to patient
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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 in 10% of adults post-transplant. A range of 1 to 20% 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 with lymph nodes, other organs are very commonly affected as well – a phenomenon called ‘extranodal’ involvement. These include the brain, lungs and the 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% in patients with solid organ transplants and 90% 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. Involvement of other organs, especially the brain, has a poor prognosis.

Sources
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  • Katabathina, V., Menias, C., Pickhardt, P., Lubner, M., and S. Prasad. Complications of Immunosuppressive Therapy in Solid Organ Transplantation. Radiology Clinics of North American. 2016. 54(2):303-19.
  • Metser U, Lo G. FDG-PET/CT in abdominal post-transplant lymphoproliferative disease. Br J Radiol. 2016;89(1057):20150844.
  • Petrara, M., Giunco, S., Serraino, D., Dolcetti, R., and A. De Rossi. Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis-driven treatment. Cancer Letters. 2015. 369(1):37-44.

By Indranil Mallick, MD
 Indranil Mallick, MD, DNB, is a radiation oncologist with a special interest in lymphoma.