AIDS-Related Lymphoma

*AIDS-related lymphoma facts written by Melissa Conrad Stöppler, MD

• Lymphoma is a cancer of lymphocytes, a type of white blood cell important in the immune response.
• AIDS-related lymphoma is a lymphoma that arises in people with acquired immunodeficiency syndrome (AIDS). AIDS is caused by infection with the human immunodeficiency virus (HIV).
• AIDS-related lymphoma can occur in the lymph nodes, which contain abundant lymphocytes.
• However, it occurs in other locations in the body as well, including the bone marrow, liver, meninges (thin membranes that cover the brain), and gastrointestinal tract.
• AIDS-related lymphoma is typically a non-Hodgkin type lymphoma.
• AIDS-related lymphoma in the central nervous system (CNS) is called AIDS-related primary CNS lymphoma.
• Signs and symptoms include fever, weight loss, and night sweats. Painless, enlarged lymph nodes may also be present.
• Treatments for AIDS-related lymphoma include chemotherapy, radiation therapy, targeted therapy, and stem cell transplant in addition to antiretroviral treatments for the HIV infection.

AIDS is caused by the human immunodeficiency virus (HIV), which attacks and weakens the body's immune system. The immune system is then unable to fight infection and disease. People with HIV disease have an increased risk of infection and lymphoma or other types of cancer. A person with HIV disease who develops certain types of infections or cancer is then diagnosed with AIDS. Sometimes, people are diagnosed with AIDS and AIDS-related lymphoma at the same time. For information about AIDS and its treatment, please see the AIDSinfo website.

AIDS-related lymphoma is a type of cancer that affects the lymph system, which is part of the body's immune system. The immune system protects the body from foreign substances, infection, and diseases. The lymph system is made up of the following:

• Lymph: Colorless, watery fluid that carries white blood cells called lymphocytes through the lymph system. Lymphocytes protect the body against infections and the growth of tumors.
• Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream.
• Lymph nodes: Small, bean-shaped structures that filter lymph and store white blood cells that help fight infection and disease. Lymph nodes are located along the network of lymph vessels found throughout the body. Clusters of lymph nodes are found in the neck, underarm, abdomen, pelvis, and groin.
• Spleen: An organ that makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. The spleen is on the left side of the abdomen near the stomach.
• Thymus: An organ in which lymphocytes grow and multiply. The thymus is in the chest behind the breastbone.
• Tonsils: Two small masses of lymph tissue at the back of the throat. The tonsils make lymphocytes.
• Bone marrow: The soft, spongy tissue in the center of large bones. Bone marrow makes white blood cells, red blood cells, and platelets.

Lymph tissue is also found in other parts of the body such as the brain, stomach, thyroid gland, and skin.

Sometimes AIDS-related lymphoma occurs outside the lymph nodes in the bone marrow, liver, meninges (thin membranes that cover the brain) and gastrointestinal tract. Less often, it may occur in the anus, heart, bile duct, gingiva, and muscles.

Lymphomas are divided into two general types:

• Hodgkin lymphoma.
• Non-Hodgkin lymphoma.

Both Hodgkin lymphoma and non-Hodgkin lymphoma may occur in patients with AIDS, but non-Hodgkin lymphoma is more common. When a person with AIDS has non-Hodgkin lymphoma, it is called AIDS-related lymphoma. When AIDS-related lymphoma occurs in the central nervous system (CNS), it is called AIDS-related primary CNS lymphoma.

Non-Hodgkin lymphomas are grouped by the way their cells look under a microscope. They may be indolent (slow-growing) or aggressive (fast-growing). AIDS-related lymphomas are aggressive. There are two main types of AIDS-related non-Hodgkin lymphoma:

• Diffuse large B-cell lymphoma (including B-cell immunoblastic lymphoma).
• Burkitt or Burkitt-like lymphoma.

These and other signs and symptoms may be caused by AIDS-related lymphoma or by other conditions. Check with your doctor if you have any of the following:

• Weight loss or fever for no known reason.
• Night sweats.
• Painless, swollen lymph nodes in the neck, chest, underarm, or groin.
• A feeling of fullness below the ribs.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the sample made up of red blood cells.
• HIV test: A test to measure the level of HIV antibodies in a sample of blood. Antibodies are made by the body when it is invaded by a foreign substance. A high level of HIV antibodies may mean the body has been infected with HIV.
• Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells. One of the following types of biopsies may be done:
  • Excisional biopsy: The removal of an entire lymph node.
  • Incisional biopsy: The removal of part of a lymph node.
  • Core biopsy: The removal of tissue from a lymph node using a wide needle.
  • Fine-needle aspiration (FNA) biopsy: The removal of tissue from a lymph node using a thin needle.
• Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow and bone under a microscope to look for signs of cancer.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

The prognosis (chance of recovery) and treatment options depend on the following:

• The stage of the cancer.
• The age of the patient.
• The number of CD4 lymphocytes (a type of white blood cell) in the blood.
• The number of places in the body lymphoma is found outside the lymph system.
• Whether the patient has a history of intravenous (IV) drug use.
• The patient's ability to carry out regular daily activities.

The process used to find out if cancer cells have spread within the lymph system or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment, but AIDS-related lymphoma is usually advanced when it is diagnosed.

The following tests and procedures may be used in the staging process:

• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease. The blood sample will be checked for the level of LDH (lactate dehydrogenase).
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the lung, lymph nodes, and liver, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium is injected into the patient through a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Lumbar puncture: A procedure used to collect cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that the cancer has spread to the brain and spinal cord. The sample may also be checked for Epstein-Barr virus. This procedure is also called an LP or spinal tap.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Stages of AIDS-related lymphoma may include E and S.

AIDS-related lymphoma may be described as follows:

• E: "E" stands for extranodal and means the cancer is found in an area or organ other than the lymph nodes or has spread to tissues beyond, but near, the major lymphatic areas.
• S: "S" stands for spleen and means the cancer is found in the spleen.

Stage I

Stage I AIDS-related lymphoma is divided into stage I and stage IE.

• Stage I: Cancer is found in one lymphatic area (lymph node group, tonsils and nearby tissue, thymus, or spleen).
• Stage IE: Cancer is found in one organ or area outside the lymph nodes.

Stage II

Stage II AIDS-related lymphoma is divided into stage II and stage IIE.

• Stage II: Cancer is found in two or more lymph node groups either above or below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).
• Stage IIE: Cancer is found in one or more lymph node groups either above or below the diaphragm. Cancer is also found outside the lymph nodes in one organ or area on the same side of the diaphragm as the affected lymph nodes.

Stage III

Stage III AIDS-related lymphoma is divided into stage III, stage IIIE, stage IIIS, and stage IIIE+S.

• Stage III: Cancer is found in lymph node groups above and below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).
• Stage IIIE: Cancer is found in lymph node groups above and below the diaphragm and outside the lymph nodes in a nearby organ or area.
• Stage IIIS: Cancer is found in lymph node groups above and below the diaphragm, and in the spleen.
• Stage IIIE+S: Cancer is found in lymph node groups above and below the diaphragm, outside the lymph nodes in a nearby organ or area, and in the spleen.

Stage IV

In stage IV AIDS-related lymphoma, the cancer:

• is found throughout one or more organs that are not part of a lymphatic area (lymph node group, tonsils and nearby tissue, thymus, or spleen) and may be in lymph nodes near those organs; or
• is found in one organ that is not part of a lymphatic area and has spread to organs or lymph nodes far away from that organ; or
• is found in the liver, bone marrow, cerebrospinal fluid (CSF), or lungs (other than cancer that has spread to the lungs from nearby areas).

Patients who are infected with the Epstein-Barr virus or whose AIDS-related lymphoma affects the bone marrow have an increased risk of the cancer spreading to the central nervous system (CNS).

For treatment, AIDS-related lymphomas are grouped based on where they started in the body, as follows:

Peripheral/systemic lymphoma

Lymphoma that starts in the lymph system or elsewhere in the body, other than the brain, is called peripheral/systemic lymphoma. It may spread throughout the body, including to the brain or bone marrow. It is often diagnosed in an advanced stage.

Primary CNS lymphoma

Primary CNS lymphoma starts in the central nervous system (brain and spinal cord). It is linked to the Epstein-Barr virus. Lymphoma that starts somewhere else in the body and spreads to the central nervous system is not primary CNS lymphoma.

Different types of treatment are available for patients with AIDS-related lymphoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Treatment of AIDS-Related lymphoma combines treatment of the lymphoma with treatment for AIDS.

Patients with AIDS have weakened immune systems and treatment can cause the immune system to become even weaker. For this reason, treating patients who have AIDS-related lymphoma is difficult and some patients may be treated with lower doses of drugs than lymphoma patients who do not have AIDS.

Combined antiretroviral therapy (cART) is used to lessen the damage to the immune system caused by HIV. Treatment with combined antiretroviral therapy may allow some patients with AIDS-related lymphoma to safely receive anticancer drugs in standard or higher doses. In these patients, treatment may work as well as it does in lymphoma patients who do not have AIDS. Medicine to prevent and treat infections, which can be serious, is also used.

For more information about AIDS and its treatment, please see the AIDSinfo website.

Four types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug.

The way the chemotherapy is given depends on where the cancer has formed. Intrathecal chemotherapy may be used in patients who are more likely to have lymphoma in the central nervous system (CNS).

Chemotherapy is used in the treatment of AIDS-related peripheral/systemic lymphoma. It is not yet known whether it is best to give combined antiretroviral therapy at the same time as chemotherapy or after chemotherapy ends.

Colony-stimulating factors are sometimes given together with chemotherapy. This helps lessen the side effects chemotherapy may have on the bone marrow.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on where the cancer has formed. External radiation therapy is used to treat AIDS-related primary CNS lymphoma.

High-dose chemotherapy with stem cell transplant

High-dose chemotherapy with stem cell transplant is a way of giving high doses of chemotherapy and replacing blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is a type of targeted therapy.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. These may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Rituximab is used in the treatment of AIDS-related peripheral/systemic lymphoma.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

AIDS-Related Peripheral/Systemic Lymphoma

Treatment of AIDS-related peripheral/systemic lymphoma may include the following:

• Combination chemotherapy with or without targeted therapy.
• High-dose chemotherapy and stem cell transplant, for lymphoma that has not responded to treatment or has come back.
• Intrathecal chemotherapy for lymphoma that is likely to spread to the central nervous system (CNS).

AIDS-Related Primary Central Nervous System Lymphoma

Treatment of AIDS-related primary central nervous system lymphoma may include the following:

• External radiation therapy.