Primary central nervous system lymphoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Overview

The treatment of primary central nervous system lymphoma depends on the patient’s age, performance status, stage and location of the lymphoma, and whether or not the individual is immunosuppressed. Chemotherapy is the mainstay of treatment for primary central nervous system lymphoma. Corticosteroids are often used to destroy lymphoma cells and relieve cerebral edema Radiation therapy may be given on its own or along with chemotherapy.

Medical Therapy

• The treatment of primary central nervous system lymphoma depends on the patient’s age, performance status, stage and location of the lymphoma, and whether or not the individual is immunosuppressed.
• Treatment of primary central nervous system lymphoma works best when the tumor has not spread outside the cerebrum and the patient is younger than 60 years, able to carry out most daily activities, and does not have AIDS or immunosuppressive disorders.

Corticosteroids

• Corticosteroids are often used to treat primary central nervous system lymphoma.
• When primary CNS lymphoma is suspected, corticosteroids are usually not given until after diagnostic tests are done because these drugs can significantly decrease the size of tumors and affect test results.
• Drugs like prednisone are used to:

• destroy lymphoma cells
• relieve edema of the brain tissue

Chemotherapy

• Chemotherapy is the mainstay of treatment for primary central nervous system lymphoma. The chemotherapy drugs commonly used for non-Hodgkin lymphoma are not effective against primary central nervous system lymphoma because these drugs do not reach the brain or cross the blood-brain barrier. Chemotherapy drugs used to treat brain tumors because they can cross the blood-brain barrier include:

• High-dose methotrexate with leucovorin (folinic acid) rescue

• Methotrexate is an important chemotherapy drug for treating primary central nervous system lymphoma.
• It may be used alone or in combination with other chemotherapy drugs.
• It is given intravenously.

• High dose cytarabine

• Primary central nervous system lymphoma may also be treated with intrathecal chemotherapy or with intraventricular chemotherapy via an Ommaya reservoir, when lymphoma cells are present in the cerebrospinal fluid (CSF). Whether or not intrathecal or intraventricular chemotherapy is used can also depend on the dose of methotrexate that has been given.

Radiation Therapy

• External beam radiation therapy may also be offered for primary central nervous system lymphoma.
• Radiation therapy is given to the entire brain (whole-brain radiation therapy or WBRT).
• Primary central nervous system lymphoma is sensitive to radiation therapy, however patients treated with radiotherapy alone have 5-year overall survivals of 3-4% and more than 80% relapsed within 10-14 months.
• Standard radiotherapy for patients consists of 40 Gy to whole brain with an additional boost of 10-20 Gy on the tumor bed.
• Shibamoto et al. reported the recent improved results of radiation monotherapy, 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years.
• Since total irradiation dose is an important predictor of delayed neurotoxicity, a decrease in the incidence of this complication should be expected if the total irradiation dose is reduced.
• Radiation therapy may be given on its own or along with chemotherapy.
• When radiation therapy is given with chemotherapy, it is usually given after the chemotherapy treatment.
• The doses of radiation therapy and chemotherapy may need to be adjusted if both treatments are used.
• The combination of radiation therapy and chemotherapy can cause severe damage to the nervous system (neurotoxicity), especially in elderly individuals with primary CNS lymphoma. This can result in changes in cognitive functioning, dementia, behaviour changes, balance and coordination problems, and other neurologic problems.

Treatment of Recurrent Primary Central Nervous System Lymphoma

• The treatment for recurrent primary central nervous system lymphoma depends on the location of the relapse and past treatment.
• If the individual did not receive whole-brain radiation therapy as part of their initial treatment, it may be given for the relapse.
• Chemotherapy may also be used even if it had been given before, but different drugs may be tried.

Treatment in individuals with Immunosuppression

• Individuals with AIDS-related primary central nervous system lymphoma are treated identically to the individuals having a normal immune system, but the treatment is more toxic and can be less effective.
• AIDS-related primary central nervous system lymphoma is often treated with:

• Highly active antiretroviral therapy (HAART)
• Corticosteroids
• Whole-brain radiation therapy (WBRT)

• Chemotherapy may be given to certain individuals depending on the status of their immune system.
• Individuals who have had organ transplants may need to have their immunosuppressant drug dose decreased or stopped.

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Surgical resection is usually ineffective because of the depth of the tumor. Treatment with irradiation and corticosteroids often only produces a partial response, but tumor recurs in more than 90% of patients. Median survival is 10 to 18 months in immunocompetent patients, and less in those with AIDS. The addition of IV methotrexate and citrovorum may extend survival to a median of 3.5 years. If radiation is added to methotrexate, median survival may increase beyond 4 years. However, radiation is not recommended in conjunction with methotrexate because of increased risk of leukoencephalopathy and dementia in patients older than 60 years of age.

References

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