CNS Lymphoma

What Causes CNS Lymphoma?

Scientists don’t know what causes CNS lymphoma. However, some factors increase the risk of developing this rare cancer. Risk factors include:

• Sex. Men are twice as likely as women to have CNS lymphoma.
• Age. CNS lymphoma most often occurs in people in their 50s to their 70s. In people with HIV/AIDS, the average age is lower (about 45).
• Compromised immune system. People with disorders that impair the immune system are at increased risk of CNS lymphoma. These disorders include AIDS, rheumatoid arthritis, and telangiectasia.
• Organ transplants. People being treated with immune-suppressant therapies after an organ transplant are also at increased risk of CNS lymphoma.

Is CNS Lymphoma Hereditary?

Most cases of CNS lymphoma do not appear to be linked to inherited traits. Instead, researchers believe most gene changes that cause tumors come from external environmental factors or changes within cells that occur randomly and with no external trigger. 

However, there is evidence that having a family history of lymphoma increases a person’s risk of developing lymphoma. People with a parent, sibling, or child with lymphoma are more likely to have lymphoma than someone with no family history. This suggests the possibility of an inherited genetic component to the disease, but scientists have not yet discovered what it is.

How Is CNS Lymphoma Detected?

Symptoms of CNS lymphoma often develop relatively quickly over a period of weeks.

Some warning signs of CNS lymphoma may include:

• Headaches
• Nausea or vomiting
• Weakness in the legs or arms
• Vision problems

How Is CNS Lymphoma Diagnosed?

Doctors may take several different diagnostic steps when they suspect a patient may have CNS lymphoma.

• Neurological exam. A basic neurological exam will test a patient’s reflexes, balance, coordination, strength, vision, and hearing. This exam may prompt a doctor to look further for a tumor’s presence, giving a clue about the affected part of the brain.
• Imaging. Imaging technologies are non-invasive ways to look at brain tissue and possibly detect a tumor’s presence. They may also be used to judge the tumor’s size, location, and growth. Magnetic resonance imaging (MRI) uses a strong magnetic field to produce images of the brain and central nervous system. Computerized tomography (CT) scan may also be used to look for tumors.
• Laboratory tests. Blood tests may be administered to determine blood cell counts and look for the presence of HIV.
• Eye exam. This exam will look for signs of lymphoma in the eyes.
• Biopsy. Doctors may collect a sample of the lymphoma to help guide the treatment process. A surgeon may use a computer-aided technique called stereotactic biopsy to obtain the tissue sample.
• Lumbar puncture (spinal tap). This examination of the cerebrospinal fluid (CSF) may be able to detect cancer cells. 

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is CNS Lymphoma Treated?

Treatment of CNS lymphoma usually varies from other types of brain tumors. While surgery is typically the first stage of treatment for other brain tumors, it is rarely used to treat CNS lymphoma. Lymphoma tumors often have poorly defined borders, making it difficult for surgeons to remove them effectively. Lymphomas also spread through the lymph system, so the tumors are likely to recur after surgery.

Chemotherapy

Chemotherapy uses chemicals that intentionally damage the body’s cells with the expectation of healthy cells recovering from the damage more easily than tumor cells. This type of therapy is often used to treat CNS lymphoma, either by itself or in combination with radiation therapy.

Radiation Therapy

Radiation therapies involve using high-energy x-rays to target and kill tumor cells directly. Radiation is typically focused on the tumor to avoid damaging healthy cells. In the case of CNS lymphoma, the radiation is usually targeted at the entire brain. This type of radiation therapy can harm brain function, so it may be discouraged for older patients (over 60).

Medications

Corticosteroids may be used to help shrink CNS lymphoma tumors and relieve symptoms. This therapy is used in conjunction with other treatments.

How Does CNS Lymphoma Progress?

CNS lymphoma is aggressive, and no treatment will cure the disease. Most people will see an improvement after treatment, but about half will have a recurrence of their lymphoma within two years. The five-year survival rate is about 30%.

The chance of recovery from CNS lymphoma is influenced by several factors, including:

• Age. Younger patients (under 60) typically have a better prognosis.
• Patients who have a high level of functioning and relatively good overall health at the time of diagnosis have higher survival rates.
• Patients with HIV/AIDS have lower survival rates.
• CNS lymphomas that affect parts of the brain outside the cerebrum tend to have less successful outcomes.

How Is CNS Lymphoma Prevented?

There is no known way to prevent CNS lymphoma.

CNS Lymphoma Caregiver Tips

Caring for someone with a brain tumor can be even more challenging than the already high demands of caring for someone with any other type of severe and progressive illness. Along with the physical changes that make other cancers and serious illnesses so physically and emotionally exhausting to deal with, brain tumors also often produce psychological and cognitive changes in the patient that can threaten the caregiver’s well-being.

As you care for your loved one through the progressive stages of their illness, keep these tips in mind:

• Learn as much as possible about the potential effects of your loved one’s specific type of brain tumor. This will allow you to understand how the illness affects the sufferer’s behavior.
• Get help from your friends and family. Caring for a brain tumor patient is a huge task, and you shouldn’t try to do it alone.
• Take time whenever possible to step away from the patient and the illness and find time for yourself. Acknowledge that it is normal and acceptable to need occasional relief from caregiving burdens.
• Find a support group. It can be beneficial to learn that you are not alone and that other people understand what you are going through.

Some people with pituitary tumors also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with these tumors:

• People with brain tumors often experience depression or anxiety.
• Personality changes resembling bipolar disorder are sometimes an indication of a brain tumor.

CNS Lymphoma Brain Science

CNS lymphoma can affect many different parts of the brain and spinal cord, and the location and size of tumors may impact symptoms.

Tumors that cause swelling or accumulation of fluid in the brain can cause general symptoms such as:

• Headaches
• Vomiting
• Vision impairment

Involvement of areas such as the pituitary gland or the hypothalamus can cause specific symptoms, including:

• Increased appetite
• Decreased sex drive
• Diabetes
• Low sodium levels in the bloodstream

When the brainstem is affected, symptoms may include:

• Dizziness
• Unsteady walking
• Problems controlling eye movements

Spinal cord involvement may cause:

• Weakness
• Loss of feeling in the extremities
• Incontinence

CNS Lymphoma Research

Title: Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS Lymphoma

Stage: Recruiting

Principal investigator: James Rubenstein, MD, PhD

University of California, San Francisco

San Francisco, CA

This phase I trial evaluates the feasibility of using hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing patients with primary central nervous system lymphoma. This trial aims to see whether MRI using hyperpolarized carbon-13 pyruvate is safe and useful for detecting central nervous system lymphoma and evaluating response to treatment.

Title: Axi-cel in CNS Lymphoma

Stage: Recruiting

Principal Investigator: Caron Jacobson, MD

Dana Farber Cancer Institute

Boston, MA  

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. “Investigational” means the drug is being studied. This study will examine the safety and efficacy of Axi-cel in participants who either currently or previously had had central nervous system involvement of their lymphoma.

The name of the study drug involved in this study is Axi-cel. Axi-cel is a chimeric antigen receptor (CAR) T-cell therapy manufactured using a person’s white blood cells. A virus is used to introduce a gene that creates a protein (called a CAR) on the surface of T cells, a type of blood cell that fights infection and can eliminate cancer cells. The CAR on the T cells may bind to and kill cells that express CD19, a molecule found on B-cell lymphomas. CAR-T cells (including Axi-cel) designed to target CD19, a protein present on B lymphocytes, have been used to treat patients with CD19+ tumors. This adoptive cell therapy (ACT) approach has shown significant and durable clinical benefits in treating CD19+ tumors. Axi-cel has been FDA approved to treat relapsed and refractory aggressive B cell lymphomas that occur outside the central nervous system and have recurred after two or more prior therapies.

Participants will receive two chemotherapy medicines: Fludarabine and Cyclophosphamide. These drugs are not intended as a direct cancer treatment but instead to help Axi-cel work with less interference from immune system cells.

The research study procedures include screening for eligibility and study treatment, including leukapheresis, evaluations, and follow-up visits.

Participants in this study will be divided into groups (cohorts) based on the type of disease they have and their treatment history.

Cohort 1: Participants with relapsed/refractory primary CNSL (PCNSL) and secondary CNSL without evidence of lymphoma outside the central nervous system

Cohort 2: Participants with relapsed/refractory lymphoma outside the central nervous system, with either active or previously treated involvement of the central nervous system by the lymphoma

Participants will receive study treatment once and will be followed for up to 15 years.

It is expected that about 18 people will take part in this research study.

Kite Pharma, a pharmaceutical company, is supporting this research study by providing Axi-cel.

Title: Acalabrutinib and Durvalumab in Primary and Secondary Central Nervous System Lymphoma

Stage: Recruiting

Principal investigator: Neha Mehta-Shah, MD

Washington University School of Medicine

Saint Louis, MO

BTK inhibition and checkpoint blockade are promising classes of therapy for central nervous system (CNS) lymphoma and have demonstrated efficacy with acceptable toxicity. A multidrug approach may carry a higher chance of durable efficacy in this aggressive disease with significant morbidity and mortality. Given the poor outcomes and limited options for patients who are not candidates for high-dose methotrexate, the investigators seek to evaluate the combination in this patient population.