AIDS-Related Lymphoma

AIDS-related lymphoma is a disease in which malignant (cancer) cells form in the lymphatic system of patients who have acquired immunodeficiency syndrome (AIDS).

AIDS is caused by the human immunodeficiency virus (HIV), which attacks and weakens the body's immune system. Lymphomas are cancers that affect the white blood cells of the lymphatic system, a part of the body's immune system. Infection with HIV greatly increases the risk of lymphoma.^[1] Sometimes, people are diagnosed with AIDS and AIDS-related lymphoma at the same time.

Lymphatic system; drawing shows the lymph vessels and lymph organs including the lymph nodes, tonsils, thymus, spleen, and bone marrow. One inset shows the inside structure of a lymph node and the attached lymph vessels with arrows showing how the lymph moves into and out of the lymph node. Another inset shows a close up of bone marrow with blood cells. Source:NIH

Types

Lymphomas are divided into two general types: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Both types may occur in AIDS patients, but NHL is more common. When a person with AIDS has NHL, it is called an AIDS-related lymphoma.

NHLs are grouped by the way their cells look under a microscope. They may be indolent (slow-growing) or aggressive (fast-growing). AIDS-related lymphoma is usually aggressive. There are three main types of AIDS-related lymphoma: diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, and small non- cleaved cell lymphoma.

Possible signs of AIDS-related lymphoma include weight loss, fever, and night sweats.

Signs and Symptoms

These and other symptoms may be caused by AIDS-related lymphoma. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

• 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.

Diagnosis

Tests that examine the body and lymph system are used to help diagnose AIDS-related lymphoma.

The following tests and procedures may be used:

Physical exam and history

A physical exam of the body will be performed 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)

This is 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.

In lymphoma diagnosis, the white blood cells are of special interest and are often subjected to more extensive examinations such as gene expression profiling or flow cytometry.^[2]

Lymph node biopsy

The removal of all or part of a lymph node may be performed. 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 biopsy(FNA): The removal of tissue from a lymph node using a thin needle.

Bone marrow aspiration and biopsy

In this procedure, bone marrow, blood, and a small piece of bone are removed by inserting a hollow needle into the hipbone or breastbone. A pathologist views the tissue samples under a microscope to look for abnormal cells.

HIV test

A test is conducted 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.

Epstein-Barr virus (EBV) test

This test examines the level of EBV antibodies in a sample of blood, tissue, or cerebrospinal fluid (CSF). Antibodies are made by the body when it is invaded by a foreign substance. A high level of EBV antibodies may mean the body has been infected with EBV.

Chest x-ray

An x-ray of the organs and bones inside the chest is performed to help determine the presence of lymphoma.

Stages of AIDS-Related Lymphoma

After AIDS-related lymphoma has been diagnosed, tests are done to find out if cancer cells have spread within the lymph system or to other parts of the body. Also at this time a determination of the stage of cancer is made. The information gathered from the staging process helps determine the treatment plan. It is important to note, however, that AIDS-related lymphoma is usually advanced when it is diagnosed. The following tests and procedures may be used in the staging process:

• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, 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): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. An imaging dye 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).
• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.
• Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
• 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 in the organ or tissue that makes it. The blood sample will be checked for the level of LDH (lactate dehydrogenase).

AIDS-related lymphoma may be described as either "E" or "S," denoting extranodal or spleen, respectively. Extranodal indicates that 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. Spleen involvement means the cancer is found in the spleen.

The following stages are used for AIDS-related lymphoma:

• Stage I disease is divided into stage I and stage IE. In Stage I disease, cancer is found in one lymph node group. In Stage IE, cancer is found in an area or organ other than the lymph nodes.

• Stage II disease is divided into stage II and stage IIE. Stage II: Cancer is found in two or more lymph node groups on the same side of the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen). In Stage IIE disease, cancer is found in an area or organ other than the lymph nodes and in lymph nodes near that area or organ, and may have spread to other lymph node groups on the same side of the diaphragm.

• Stage III disease is present when cancer is in lymph node groups on both sides of the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen). In Stage IIIE disease, cancer is found in lymph node groups on both sides of the diaphragm and in an area or organ other than the lymph nodes. In Stage IIIS disease, cancer is found in lymph node groups on both sides of the diaphragm and in the spleen. In Stage IIIS+E disease, cancer is found in lymph node groups on both sides of the diaphragm, in an area or organ other than the lymph nodes, and in the spleen.

• Stage IV disease is either found throughout one or more organs other than the lymph nodes and may be in lymph nodes near those organs; or found in one organ other than the lymph nodes and has spread to lymph nodes far away from that organ.

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).

Treatment

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

• Peripheral/systemic lymphoma

This type of lymphoma starts in lymph nodes or other organs of the lymph system is called peripheral/systemic lymphoma. The lymphoma may spread throughout the body, including to the brain or bone marrow.

• Primary CNS lymphoma starts in the central nervous system (brain and spinal cord). Lymphoma that starts somewhere else in the body and spreads to the central nervous system is not primary CNS lymphoma.

There is no standard treatment plan for AIDS-related peripheral/systemic lymphoma. Treatment is adjusted for each patient and usually includes one or more of the following:

Chemotherapy

This is a type of 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 spinal column (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 the type and stage of the cancer being treated.

Intrathecal chemotherapy

This type of chemotherapy may be used in patients who are more likely to have lymphoma in the central nervous system (CNS).

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 the type and stage of the cancer being treated.

High-dose chemotherapy with stem cell transplant

This method involves 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.

New types of treatment are being tested in clinical trials. These include the following:

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.

In general, AIDS-related lymphoma combines treatment of the lymphoma with treatment for AIDS; this can amount to very aggressive use of potentially dangerous drugs. For this reason, patients who have AIDS-related lymphoma are usually treated with lower doses of drugs than lymphoma patients who do not have AIDS.

Highly-active antiretroviral therapy (HAART) is used to slow progression of HIV (which is a retrovirus). Treatment with HAART may allow some patients to safely receive anticancer drugs in standard or higher doses. Medicine to prevent and treat infections, which can be serious, is also used.

AIDS-related lymphoma usually grows faster than lymphoma that is not AIDS-related and it is more likely to spread to other parts of the body. In general, AIDS-related lymphoma is harder to treat.

Treatment of AIDS-related primary central nervous system lymphoma is usually radiation therapy.

Clinical Trials

Clinical trials are taking place in many parts of the country. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

• Gene Therapy-Treated Stem Cells in Treating Patients Undergoing Stem Cell Transplant for Intermediate-Grade or High-Grade AIDS-Related Lymphoma
• Carmustine, Etoposide, Cyclophosphamide, and Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma

Expected Outcome

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

• The stage of the cancer.
• The number of CD4 lymphocytes (a type of white blood cell) in the blood.
• Whether the patient has ever had AIDS-related infections.
• The patient's ability to carry out regular daily activities.

References

1. ↑ Grogg KL, Miller RF, Dogan A. HIV infection and lymphoma. J Clin Pathol. 2007 Dec;60(12):1365-72. Abstract
2. ↑ Dunphy CH. Gene expression profiling data in lymphoma and leukemia: review of the literature and extrapolation of pertinent clinical applications. Arch Pathol Lab Med. 2006 Apr;130(4):483-520. Abstract | PDF

Other Resources

• National Cancer Institute
• Lymphoma Information Network