Primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is an uncommon type of non-Hodgkin lymphoma (NHL). It starts in the brain or spinal cord (called the central nervous system, or CNS), in the membranes that cover and protect the brain and spinal cord (called the meninges) or in the eyes. It rarely spreads, or metastasizes, outside of the CNS.

Most PCNSLs are B-cell lymphomas, usually diffuse large B-cell lymphomas (DLBCL). T-cell PCNSL is rare.

PCNSL is more common in older adults. The average age at diagnosis is 65.

The main risk for developing PCNSL is a weakened, or suppressed, immune system. It often develops in people who have:

• acquired immunodeficiency syndrome (AIDS)
• a weakened immune system because they are taking medicines to lower the risk that their body will reject a donated organ
• an inherited disorder that weakens the immune system

The treatments offered for PCNSL depend on your age and performance status. Doctors will also consider how well your body can fight infections if your immune system is weakened (you are immunosuppressed).

People with AIDS-related PCNSL are given the same treatments as people who have a normal immune system. These treatments cause more and worse side effects and can be less effective in people who have AIDS. AIDS-related PCNSL is often treated with highly active antiretroviral therapy (HAART), as well as corticosteroids and radiation to all of the brain (called whole-brain radiation therapy, or WBRT). Some people may be offered chemotherapy depending on how well their immune system is working.

People who develop PCNSL after an organ transplant may need to lower the dose of or stop taking their immunosuppressant drug.

A corticosteroid is any steroid hormone that acts as an anti-inflammatory by reducing swelling and lowering the body’s immune response (the immune system’s reaction to the presence of foreign substances). PCNSL responds very well to corticosteroid therapy. Drugs like prednisone are used to destroy lymphoma cells and reduce swelling of the brain tissue.

Corticosteroids are usually not given until after diagnostic tests confirm that you have PCNSL. This is because these drugs can significantly shrink tumours and affect test results.

Certain chemotherapy drugs need to be used to treat PCNSL because they can cross the blood-brain barrier. The blood-brain barrier is a network of blood vessels and cells that filters blood flowing to the brain. It makes it hard for some substances (such as anticancer drugs) to enter the brain.

Either of the following can be used to treat PCNSL:

• high-dose methotrexate with leucovorin (folinic acid) alone or with other chemotherapy drugs
• high-dose cytarabine (Cytosar, Ara-C)

These drugs may be given directly into the cerebrospinal fluid (CSF) if there are lymphoma cells in the CSF. They may be given as intrathecal chemotherapy. This means that the chemotherapy drugs are injected directly into the CSF. They may also be given as intraventricular chemotherapy. This means that the drugs are given directly into the CSF through a small device called an Ommaya reservoir.

External beam radiation therapy is sometimes given as WBRT to treat PCNSL. Radiation therapy may also be used to treat PCNSL that starts in the eyes.

Radiation therapy may be given on its own or with chemotherapy. When both radiation therapy and chemotherapy are used, radiation therapy is usually given after chemotherapy. The doses of radiation therapy and chemotherapy may need to be adjusted if both treatments are used.

The combination of radiation therapy and chemotherapy often causes harmful side effects to the nervous system (called neurotoxicity). These side effects can include changes in cognitive function, dementia, behaviour changes, balance and coordination problems and other neurologic problems. The elderly are most at risk for these nervous system problems.

WBRT may be given when PCNSL comes back (recurs) after treatment, even though there is the risk of nervous system problems.