AIDS-Related Lymphoma Treatment (PDQ®)


Information for: Patients | Healthcare Professionals

General Information About AIDS-Related Lymphoma

AIDS-related lymphoma is a disease in which malignant (cancer) cells form in the lymph 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. The immune system is then unable to fight infection and diseases that invade the body. People with HIV disease have an increased risk of developing infections, lymphoma, and 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 Web site.

Lymphomas are cancers that affect the white blood cells of the lymph system, part of the body's immune system. The lymph system is made up of the following:

  • Lymph: Colorless, watery fluid that travels through the lymph system and carries white blood cells called lymphocytes. 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 underarm, pelvis, neck, abdomen, 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 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 (clear fluid) moves into and out of the lymph node. Another inset shows a close up of bone marrow with blood cells.
Anatomy of the lymph system, showing the lymph vessels and lymph organs including lymph nodes, tonsils, thymus, spleen, and bone marrow. Lymph (clear fluid) and lymphocytes travel through the lymph vessels and into the lymph nodes where the lymphocytes destroy harmful substances. The lymph enters the blood through a large vein near the heart.

There are many different types of lymphoma.

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

For more information, see the following PDQ summaries:

  • Adult Non-Hodgkin Lymphoma Treatment
  • Childhood Non-Hodgkin Lymphoma Treatment
  • Primary CNS Lymphoma Treatment

AIDS-related lymphomas grow and spread quickly.

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 lymphoma is usually aggressive. There are three main types of AIDS-related lymphoma:

  • Diffuse large B-cell lymphoma.
  • B-cellimmunoblastic lymphoma.
  • Small non-cleaved cell lymphoma.

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

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. (For more information, see the PDQ summary on Sweats and Hot Flashes.)
  • Painless, swollen lymph nodes in the neck, chest, underarm, or groin.
  • A feeling of fullness below the ribs.

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

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.
    Complete blood count (CBC); left panel shows blood being drawn from a vein on the inside of the elbow using a tube attached to a syringe; right panel shows a laboratory test tube with blood cells separated into layers: plasma, white blood cells, platelets, and red blood cells.
    Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
  • 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, 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 signs of cancer.
    Bone marrow aspiration and biopsy; drawing shows a patient lying face down on a table and a Jamshidi needle (a long, hollow needle) being inserted into the hip bone. Inset shows the Jamshidi needle being inserted through the skin into the bone marrow of the hip bone.
    Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
  • 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.
  • 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.

Certain factors affect prognosis (chance of recovery) and treatment options.

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.

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.

The process used to find out if cancercells 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-relatedlymphoma 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 in the organ or tissue that makes it. 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 malignanttumor cells in the body. A small amount of radioactiveglucose (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. 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 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. A pathologist views the cerebrospinal fluid under a microscope to look for signs of cancer.
    Lumbar puncture; drawing shows a patient lying in a curled position on a table and a spinal needle (a long, thin needle) being inserted into the lower back. Inset shows a close-up of the spinal needle inserted into the cerebrospinal fluid (CSF) in the lower part of the spinal column.
    Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.

There are three ways that cancer spreads in the body.

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.

The following stages are used for AIDS-related lymphoma:

Stage I

Stage I AIDS-related lymphoma; drawing shows cancer in one lymph node group above the diaphragm. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node.
Stage I AIDS-related lymphoma. Cancer is found in one lymphatic area (lymph nodes, tonsils, thymus, or spleen). In stage IE (not shown), cancer is found in one organ or area outside the lymph nodes.

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 II AIDS-related lymphoma; drawing shows cancer in lymph node groups above and below the diaphragm. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node.
    Stage II AIDS-related lymphoma. Cancer is found in two or more lymph node groups, and both are either above (a) or below (b) the diaphragm.
  • 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 IIE AIDS-related lymphoma; drawing shows cancer in one lymph node group above the diaphragm and in the left lung. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node.
    Stage IIE AIDS-related lymphoma. Cancer is found in one or more lymph node groups either above or below the diaphragm and outside the lymph nodes in an organ or area on the same side of the diaphragm as the lymph nodes with cancer (a).

Stage III

Stage III AIDS-related lymphoma; drawing shows cancer in lymph node groups above and below the diaphragm, in the left lung, and in the spleen. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node.
Stage III AIDS-related lymphoma. Cancer is found in one or more lymph node groups above and below the diaphragm (a). In 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 (b). In stage IIIS, cancer is found in lymph node groups above and below the diaphragm (a) and in the spleen (c). In stage IIIE plus S, cancer is found in lymph node groups above and below the diaphragm, outside the lymph nodes in a nearby organ or area (b), and in the spleen (c).

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

Stage IV AIDS-related lymphoma; drawing shows cancer in the liver, the left lung, and in one lymph node group below the diaphragm. The brain and pleura are also shown. One inset shows a close-up of cancer spreading through lymph nodes and lymph vessels to other parts of the body. Lymphoma cells containing cancer are shown inside one lymph node. Another inset shows cancer cells in the bone marrow.
Stage IV AIDS-related lymphoma. Cancer is found throughout one or more organs that are not part of a lymphatic area (lymph nodes, tonsils, thymus, or spleen) (a); or in one organ that is not part of a lymphatic area and has spread to lymph nodes far away from that organ (b); or cerebrospinal fluid (not shown), the liver, bone marrow, or lungs.

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 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

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.

Treatment Option Overview

There are different types of treatment for patients with AIDS-related lymphoma.

Different types of treatment are available for patients with AIDS-relatedlymphoma. 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 further damage. 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.

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

Three 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 the type and stage of the cancer being treated.

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

Intrathecal chemotherapy; drawing shows the cerebrospinal fluid (CSF) in the brain and spinal cord, and an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). Top section shows a syringe and needle injecting anticancer drugs into the Ommaya reservoir. Bottom section shows a syringe and needle injecting anticancer drugs directly into the cerebrospinal fluid in the lower part of the spinal column.
Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed.

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

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.

Stem Cell Transplant

Drawing of stem cells being removed from a patient or donor. Blood is collected from a vein in the arm and flows through a machine that removes the stem cells; the remaining blood is returned to a vein in the other arm. Drawing of a health care provider giving a patient treatment to kill blood-forming cells. Chemotherapy is given to the patient through a catheter in the chest. Drawing of stem cells being given to the patient through a catheter in the chest.

Stem cell transplant (Step 1). Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.

Stem cell transplant (Step 2). The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown).

Stem cell transplant (Step 3). The patient receives stem cells through a catheter placed into a blood vessel in the chest.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

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 antibodytherapy is one type of targeted therapy being studied in the treatment of AIDS-related lymphoma.

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.

Patients may want to think about taking part in a clinical trial.

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.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

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. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

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. This is sometimes called re-staging.

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.

Treatment Options for AIDS-Related Lymphoma

AIDS-Related Peripheral/Systemic Lymphoma

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

  • Combination chemotherapy.
  • High-dose chemotherapy and stem cell transplant.
  • A clinical trial of monoclonal antibodies.
  • A clinical trial of different treatment combinations.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with AIDS-related peripheral/systemic lymphoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

AIDS-Related Primary Central Nervous System Lymphoma

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

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with AIDS-related primary CNS lymphoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About AIDS-Related Lymphoma

For more information from the National Cancer Institute about AIDS-related lymphoma, see the following.

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on November 19, 2013.


General Information About AIDS-Related Lymphoma

The AIDS was first described in 1981, and the first definitions included certain opportunistic infections, Kaposi sarcoma, and central nervous system (CNS) lymphomas. In 1984, a multicenter study described the clinical spectrum of non-Hodgkin lymphomas (NHLs) in the populations at risk for AIDS.[1] In 1985 and 1987, the Centers for Disease Control and Prevention (CDC) revised the definition of AIDS to include human immunodeficiency virus (HIV)-infected patients who had aggressive B-cell NHL. The incidence of NHL has increased in an almost parallel course with the AIDS epidemic and accounts for 2% to 3% of newly diagnosed AIDS cases.[2]

Pathologically, AIDS-related lymphomas are comprised of a narrow spectrum of histologic types consisting almost exclusively of B-cell tumors of aggressive type. These include the following:

  • Diffuse large B-cell lymphoma.
  • B-cell immunoblastic lymphoma.
  • Small noncleaved lymphoma, either Burkitt or Burkitt-like.

The HIV-associated lymphomas can be categorized into the following:

  • Aggressive B-cell lymphoma.
  • Primary central nervous system lymphoma (PCNSL), which represents 20% of all NHL cases in AIDS patients.
  • Primary effusion lymphoma.
  • Plasmablastic multicentric Castleman disease.
  • Hodgkin lymphoma.

Primary effusion lymphoma has been associated with Kaposi sarcoma-associated herpes-virus/human herpes virus type-8 (KSHV/HHV-8).[3][4] Primary effusion lymphoma presents as a liquid phase spreading along serous membranes in the absence of masses or adenopathy.[3] In addition to HHV-8, many cases are also associated with Epstein-Barr virus. Extension of lymphoma from the effusion to underlying tissue may occur. Plasmablastic multicentric Castleman disease is also associated with a coinfection of KSHV/HHV-8 and HIV.[5][6] Patients typically present with fever, night sweats, weight loss, lymphadenopathy, and hepatosplenomegaly. Patients may progress to primary effusion lymphoma or to plasmablastic or anaplastic large cell lymphoma. Anecdotal responses to rituximab, an anti-CD20 monoclonal antibody, have been reported.[5][Level of evidence: 3iiiDiv]

An international database of 48,000 HIV-seropositive individuals from the United States, Europe, and Australia found a 42% decline in the incidence of NHLs from 1997 to 1999 compared with 1992 to 1996, both for PCNSL and for systemic lymphoma.[7] The introduction of highly active antiretroviral therapy (HAART) is the proposed explanation for this decline.[8] The diagnosis of AIDS precedes the onset of NHL in approximately 57% of the patients, but in 30% of the patients the diagnosis of AIDS is made at the time of the diagnosis of NHL and HIV positivity.[9] The geographic distribution of these lymphomas is also similar to the geographic spread of AIDS. Unlike Kaposi sarcoma, which has a predilection for homosexual men and appears to be on the decline in incidence, all risk groups appear to have an excess number of NHLs; these risk groups include intravenous drug users and children of HIV-positive individuals.

In general, the clinical setting and response to treatment of patients with AIDS-related lymphoma is very different from that of the non-HIV patients with lymphoma. The HIV-infected individual with aggressive lymphoma usually presents with advanced-stage disease that is frequently extranodal.[10]

Common extranodal sites include the following:

  • Bone marrow.
  • Liver.
  • Meninges.
  • Gastrointestinal tract.

Very unusual sites are also characteristic and include the following:

  • Anus.
  • Heart.
  • Bile duct.
  • Gingiva.
  • Muscles.

The clinical course is more aggressive, and the disease is both more extensive and less responsive to chemotherapy. Immunodeficiency and cytopenias, common in these patients at the time of initial presentation, are exacerbated by the administration of chemotherapy. Treatment of the malignancy increases the risk of opportunistic infections that, in turn, further compromise the delivery of adequate treatment.

Prognoses of patients with AIDS-related lymphoma have been associated with the following:[11]

  • Stage (i.e., extent of disease, extranodal involvement, lactate dehydrogenase level, and bone marrow involvement).
  • Age.
  • Severity of the underlying immunodeficiency (measured by CD4 lymphocyte count in peripheral blood).
  • Performance status.
  • Prior AIDS diagnosis (i.e., history of opportunistic infection or Kaposi sarcoma).

Patients with AIDS-related PCNSL appear to have more severe underlying HIV-related disease than do patients with systemic lymphoma. In one report, this severity was evidenced by patients with PCNSL having a higher incidence of prior AIDS diagnoses (73% vs. 37%), lower median number of CD4 lymphocytes (30/dL vs. 189/dL), and a worse median survival time (2.5 months vs. 6.0 months).[12] This report also showed that patients with poor risk factors—defined as Karnofsky performance status less than 70%, history of prior AIDS diagnosis, and bone marrow involvement—had a median survival time of 4.0 months compared with a good prognosis group without any of these risk factors, who had a median survival time of 11.3 months.

In another report (NIAID-ACTG-142), prognostic factors were evaluated in a group of 192 patients with newly diagnosed AIDS-related lymphoma who were randomly assigned to receive either low-dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) or standard dose m-BACOD with granulocyte-macrophage colony-stimulating factor.[13] No differences existed between these two treatments in terms of efficacy for disease-free survival, median survival, or risk ratio for death.[13][Level of evidence: 1iiA] On multivariate analysis, factors associated with decreased survival included age older than 35 years, history of intravenous drug use, stage III or stage IV disease, and CD4 counts of less than 100 cells/mm3. The median survival rates were 46 weeks for patients with one or no risk factors, 44 weeks for patients with two risk factors, and 18 weeks for patients with three or more risk factors. The International Prognostic Index may also be predictive for survival.[14][15][16] In a multicenter cohort study of 203 patients, in a multivariable Cox model, response to HAART was independently associated with prolonged survival (relative hazard = 0.32; 95% confidence interval, 0.16–0.62).[17][Level of evidence: 3iiiDii]

HIV-associated Hodgkin lymphoma

Multiple reviews of Hodgkin lymphoma occurring in patients at risk for AIDS have been done;[18][19] however, Hodgkin lymphoma is still not part of the CDC definition of AIDS because of no clear demonstration of its increased incidence in conjunction with HIV, as is the case for aggressive NHL. The CDC, in conjunction with the San Francisco Department of Public Health, has reported a cohort study in which HIV-infected men had an excess risk that was attributable to the HIV infection of 19.3 cases of Hodgkin lymphoma per 100,000 person-years and 224.9 cases of NHL per 100,000 person-years. Although an excess incidence of Hodgkin lymphoma was found in HIV-infected homosexual men in this report, additional epidemiologic studies will be needed before the CDC will reconsider Hodgkin lymphoma as an HIV-associated malignancy.[20]

HIV-associated Hodgkin lymphoma presents in an aggressive fashion, often with extranodal or bone marrow involvement.[18][19][21] A distinctive feature of HIV-associated Hodgkin lymphoma is the lower frequency of mediastinal adenopathy compared with non-HIV-associated Hodgkin lymphoma. Most patients in these series had either mixed cellularity or lymphocyte-depleted Hodgkin lymphoma, expression of Epstein-Barr virus-associated proteins in Reed-Sternberg cells, B symptoms, and a median CD4 lymphocyte count of 300/dL or less.[22] In a retrospective multicenter review of 62 patients, those receiving HAART with chemotherapy had a 74% 2-year overall survival (OS) versus a 30% OS for those not receiving HAART (P < .001).[23][Level of evidence: 3iiiA]

Related Summaries

Note: Other PDQ summaries containing information about AIDS-related lymphoma include the following:

  • Kaposi Sarcoma
  • Primary CNS Lymphoma

References:

  1. Ziegler JL, Beckstead JA, Volberding PA, et al.: Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 311 (9): 565-70, 1984.

  2. Rabkin CS, Yellin F: Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1. J Natl Cancer Inst 86 (22): 1711-6, 1994.

  3. Simonelli C, Spina M, Cinelli R, et al.: Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol 21 (21): 3948-54, 2003.

  4. Nador RG, Cesarman E, Chadburn A, et al.: Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 88 (2): 645-56, 1996.

  5. Goedert JJ: Multicentric Castleman disease: viral and cellular targets for intervention. Blood 102 (8): 2710-11, 2003.

  6. Marcelin AG, Aaron L, Mateus C, et al.: Rituximab therapy for HIV-associated Castleman disease. Blood 102 (8): 2786-8, 2003.

  7. International Collaboration on HIV and Cancer.: Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J Natl Cancer Inst 92 (22): 1823-30, 2000.

  8. Stebbing J, Gazzard B, Mandalia S, et al.: Antiretroviral treatment regimens and immune parameters in the prevention of systemic AIDS-related non-Hodgkin's lymphoma. J Clin Oncol 22 (11): 2177-83, 2004.

  9. Knowles DM, Chamulak GA, Subar M, et al.: Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS). The New York University Medical Center experience with 105 patients (1981-1986). Ann Intern Med 108 (5): 744-53, 1988.

  10. Sparano JA: Clinical aspects and management of AIDS-related lymphoma. Eur J Cancer 37 (10): 1296-305, 2001.

  11. Bower M, Gazzard B, Mandalia S, et al.: A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann Intern Med 143 (4): 265-73, 2005.

  12. Levine AM, Sullivan-Halley J, Pike MC, et al.: Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival. Cancer 68 (11): 2466-72, 1991.

  13. Kaplan LD, Straus DJ, Testa MA, et al.: Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 336 (23): 1641-8, 1997.

  14. Navarro JT, Ribera JM, Oriol A, et al.: International prognostic index is the best prognostic factor for survival in patients with AIDS-related non-Hodgkin's lymphoma treated with CHOP. A multivariate study of 46 patients. Haematologica 83 (6): 508-13, 1998.

  15. Rossi G, Donisi A, Casari S, et al.: The International Prognostic Index can be used as a guide to treatment decisions regarding patients with human immunodeficiency virus-related systemic non-Hodgkin lymphoma. Cancer 86 (11): 2391-7, 1999.

  16. Straus DJ, Huang J, Testa MA, et al.: Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142--low-dose versus standard-dose m-BACOD plus granulocyte-macrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseases. J Clin Oncol 16 (11): 3601-6, 1998.

  17. Hoffmann C, Wolf E, Fätkenheuer G, et al.: Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma. AIDS 17 (10): 1521-9, 2003.

  18. Spina M, Vaccher E, Nasti G, et al.: Human immunodeficiency virus-associated Hodgkin's disease. Semin Oncol 27 (4): 480-8, 2000.

  19. Thompson LD, Fisher SI, Chu WS, et al.: HIV-associated Hodgkin lymphoma: a clinicopathologic and immunophenotypic study of 45 cases. Am J Clin Pathol 121 (5): 727-38, 2004.

  20. Hessol NA, Katz MH, Liu JY, et al.: Increased incidence of Hodgkin disease in homosexual men with HIV infection. Ann Intern Med 117 (4): 309-11, 1992.

  21. Re A, Casari S, Cattaneo C, et al.: Hodgkin disease developing in patients infected by human immunodeficiency virus results in clinical features and a prognosis similar to those in patients with human immunodeficiency virus-related non-Hodgkin lymphoma. Cancer 92 (11): 2739-45, 2001.

  22. Dolcetti R, Boiocchi M, Gloghini A, et al.: Pathogenetic and histogenetic features of HIV-associated Hodgkin's disease. Eur J Cancer 37 (10): 1276-87, 2001.

  23. Hentrich M, Maretta L, Chow KU, et al.: Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study. Ann Oncol 17 (6): 914-9, 2006.

Cellular Classification of AIDS-Related Lymphoma

Pathologically, AIDS-related lymphomas are comprised of a narrow spectrum of histologic types consisting almost exclusively of B-cell tumors of aggressive type. These include the following:

  • Diffuse large B-cell lymphoma.
  • B-cell immunoblastic lymphoma.
  • Small noncleaved lymphoma, either Burkitt or Burkitt-like.

All three pathologic types are equally distributed and represent aggressive disease.

AIDS-related lymphomas, though usually of B-cell origin as demonstrated by immunoglobulin heavy-chain gene rearrangement studies, have also been shown to be oligoclonal and polyclonal as well as monoclonal in origin. Although human immunodeficiency virus (HIV) does not appear to have a direct etiologic role, HIV infection does lead to an altered immunologic milieu. HIV generally infects T lymphocytes whose loss of regulation function leads to hypergammaglobulinemia and polyclonal B-cell hyperplasia. B cells are not the targets of HIV infection. Instead, Epstein-Barr virus (EBV) is thought to be at least a cofactor in the etiology of some of these lymphomas. The EBV genome has been detected in varying numbers of patients with AIDS-related lymphomas; molecular analysis suggests that the cells were infected before clonal proliferation began.[1] EBV is detected in 30% of patients with small, noncleaved lymphomas and in 80% of patients with diffuse, large cell lymphomas. The rare, primary effusion lymphoma consistently harbors human herpes virus type-8 and frequently contains EBV.[2] HIV-related T-cell lymphomas have also been identified and appear to be associated with EBV infection.[3]

References:

  1. Thorley-Lawson DA, Gross A: Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 350 (13): 1328-37, 2004.

  2. Simonelli C, Spina M, Cinelli R, et al.: Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol 21 (21): 3948-54, 2003.

  3. Thomas JA, Cotter F, Hanby AM, et al.: Epstein-Barr virus-related oral T-cell lymphoma associated with human immunodeficiency virus immunosuppression. Blood 81 (12): 3350-6, 1993.

Stage Information for AIDS-Related Lymphoma

Although stage is important in selecting the treatment of patients with non-Hodgkin lymphoma (NHL) who do not have AIDS, the majority of patients with AIDS-related lymphomas have far-advanced disease.

Staging Subclassification System

Table 1. Anatomic Stage/Prognostic Groupsa

Stage

Prognostic Groups

I

Involvement of a single lymphatic site (i.e., nodal region, Waldeyer ring, thymus or spleen) (I).

OR

Localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE) (rare in Hodgkin lymphoma).

II

Involvement of two or more lymph node regions on the same side of the diaphragm (II).

OR

Localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). The number of regions involved may be indicated by a subscript Arabic numeral, for example, II3

III

Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE, IIIS). Splenic involvement is designated by the letter S.

IV

Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement.

OR

Isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant site(s). Stage IV includes any involvement of the liver or bone marrow, lungs (other than by direct extension from another site), or cerebrospinal fluid.

aReprinted with permission from AJCC: Hodgkin and non-Hodgkin lymphomas. In Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 607–11.

The Ann Arbor staging system is commonly used for patients with NHL.[1][2] In this system, stage I, II, III, and IV NHL can be subclassified into A and B categories: B for those with well-defined generalized symptoms and A for those without. The B designation is given to patients with any of the following symptoms:

  • Unexplained loss of more than 10% of body weight in the 6 months before diagnosis.
  • Unexplained fever with temperatures higher than 38° C.
  • Drenching night sweats. (Refer to the PDQ summary on Sweats and Hot Flashes for more information.)

Occasionally, specialized staging systems are used. The physician should be aware of the system used in a specific report.

The E designation is used when extranodal lymphoid malignancies arise in tissues separate from, but near, the major lymphatic aggregates. Stage IV refers to disease that is diffusely spread throughout an extranodal site, such as the liver. If pathologic proof of involvement of one or more extralymphatic sites has been documented, the symbol for the site of involvement, followed by a plus sign (+), is listed.

Table 2. Notation for Identification of Sites

N = nodes

H = liver

L = lung

M = marrow

S = spleen

P = pleura

O = bone

D = skin

Current practice assigns a clinical stage (CS) based on the findings of the clinical evaluation and a pathologic stage (PS) based on the findings made as a result of invasive procedures beyond the initial biopsy.

For example, on percutaneous biopsy, a patient with inguinal adenopathy and a positive lymphangiogram without systemic symptoms might be found to have involvement of the liver and bone marrow. The precise stage of such a patient would be CS IIA, PS IVA(H+)(M+).

A number of other factors that are not included in the above staging system are important for the staging and prognosis of patients with NHL. These factors include the following:

  • Age.
  • Performance status.
  • Tumor size.
  • Lactate dehydrogenase (LDH) values.
  • The number of extranodal sites.

To identify subgroups of patients most likely to relapse, an international prognostic index was compiled for 2,031 patients with aggressive NHL.[3] After validation by several cancer centers (NCT00003150),[4][5] the major cooperative groups used this index in the design of new clinical trials. The model has been simple to apply, reproducible, and has predicted outcome even after patients have achieved a complete remission. The model has identified five significant risk factors prognostic of overall survival (OS): age (<60 years vs. >60 years), serum LDH (normal vs. elevated), performance status (0 or 1 vs. 2–4), stage (stage I or stage II vs. stage III or stage IV), and extranodal site involvement (0 or 1 vs. 2–4).

Patients with two or more risk factors were shown to have a less than 50% chance of relapse-free and OS at 5 years. This study also identified patients at high risk of relapse based on specific sites of involvement, including bone marrow, central nervous system, liver, lung, and spleen. Patients at high risk of relapse may benefit from consolidation therapy or other approaches under clinical evaluation.[3] Molecular profiles of gene expression using DNA microarrays may help to stratify patients in the future for therapies directed at specific targets and to better predict survival after standard chemotherapy.[6][7]

References:

  1. Lymphoid neoplasms. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 599-628.

  2. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 49 (10): 2112-35, 1982.

  3. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 329 (14): 987-94, 1993.

  4. Salles G, de Jong D, Xie W, et al.: Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium. Blood 117 (26): 7070-8, 2011.

  5. Advani RH, Chen H, Habermann TM, et al.: Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol 151 (2): 143-51, 2010.

  6. Rosenwald A, Wright G, Chan WC, et al.: The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346 (25): 1937-47, 2002.

  7. Abramson JS, Shipp MA: Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach. Blood 106 (4): 1164-74, 2005.

Treatment Option Overview

The treatment of patients with AIDS-related lymphomas presents the challenge of integrating therapy appropriate for the stage and histologic subset of malignant lymphoma with the limitations imposed by HIV infection, which to date is a chronic incurable illness.[1] In addition to antitumor therapy, essential components of an optimal non-Hodgkin lymphoma treatment strategy include the following:[2]

  • Highly active antiretroviral therapy.
  • Prophylaxis for opportunistic infections.
  • Rapid recognition and treatment of intercurrent infections.

Patients with HIV positivity and underlying immunodeficiency have poor bone marrow reserve, which compromises the potential for drug dose intensity. Intercurrent opportunistic infection is a risk that may also lead to a decrease in drug delivery. Furthermore, chemotherapy itself compromises the immune system and increases the likelihood of opportunistic infection.

References:

  1. Levine AM: Acquired immunodeficiency syndrome-related lymphoma: clinical aspects. Semin Oncol 27 (4): 442-53, 2000.

  2. Tirelli U, Bernardi D: Impact of HAART on the clinical management of AIDS-related cancers. Eur J Cancer 37 (10): 1320-4, 2001.

AIDS-Related Peripheral/Systemic Lymphoma

The treatment of AIDS-related lymphomas involves overcoming several problems. These are all aggressive lymphomas, which by definition are diffuse large cell/immunoblastic lymphoma or small noncleaved cell lymphoma. These lymphomas frequently involve the bone marrow and central nervous system (CNS) and, therefore, are usually in an advanced stage. In addition, the immunodeficiency of AIDS and the leukopenia that is commonly seen with human immunodeficiency virus (HIV) infection makes the use of immunosuppressive chemotherapy difficult.

A large number of retrospective studies and several prospective studies have been reported using regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD), and infusional cyclophosphamide, doxorubicin, and etoposide.[1][2][3][4] The patients who go into remission are more likely to have less disease, no bone marrow or CNS involvement, no prior AIDS-defining illness, and a better performance status. Patients at risk for subsequent CNS involvement include those with bone marrow involvement or those with Epstein-Barr virus identified in the primary tumor or in the cerebrospinal fluid (i.e., by polymerase chain reaction).[5][6][7] Intrathecal chemotherapy is usually considered for those patients at higher risk for CNS involvement.

Prior to the highly active antiretroviral therapy (HAART) era, a randomized trial of patients with HIV and either Burkitt lymphoma (BL) or diffuse large B-cell lymphoma (DLBCL) compared standard dose chemotherapy and growth factor support with reduced-dose chemotherapy.[1] No difference was found in overall survival (OS) between the two dose levels, and no difference was observed between the historic groups (BL and DLBCL); however, the median survival was equally poor at 6 to 7 months.[1][Level of evidence: 1iiA] The introduction of HAART has led to a marked reduction in opportunistic infections, prolonged survival with HIV infection, and a median OS for patients with AIDS-related lymphoma, which is comparable to the outcome in the nonimmunosuppressed population.[4][8][9][10][11][12][13][14][Level of evidence: 3iiiDiv] The use of HAART has also allowed the use of standard dose and even intensive chemotherapy regimens to be given with reasonable safety to patients with AIDS-related lymphomas, which is comparable to the outcome in non-HIV patients.[3][4][13][14][15][16]

In a retrospective review of 363 patients with HIV-associated lymphoma, survival of patients with HIV-DLBCL improved in the HAART era, but survival of similarly treated patients with HIV-BL remained poor.[17][Level of evidence: 3iiiDiv] Future studies will evaluate if more intensive chemotherapy appropriate for non-HIV patients with BL results in better outcomes for patients with HIV-BL.[17] A prospective randomized comparison (AMC-010) of rituximab plus CHOP (R-CHOP) versus CHOP in 150 patients with HIV-DLBCL and HIV-BL showed no difference in (OS); treatment-related infectious deaths occurred in 14% of patients who received R-CHOP versus 2% of patients who received CHOP alone (P = .035).[18][Level of evidence: 1iiA] A Cochrane meta-analysis published in 2009 evaluated 857 patients in four randomized clinical trials; no clinical conclusions regarding the optimal regimen could be reached as a result of varying interventions and the lack of adequately powered trials with a low risk of bias.[19]

Highly selected patients with resistant or relapsed lymphoma after first-line chemotherapy and with continued responsiveness to HAART underwent second-line chemotherapy followed by high-dose therapy and autologous peripheral stem cell transplantation. Long-term survivors have been reported anecdotally for these highly selected patients who relapsed.[20][21][22][23][Level of evidence: 3iiiDiv]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with AIDS-related peripheral/systemic lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kaplan LD, Straus DJ, Testa MA, et al.: Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 336 (23): 1641-8, 1997.

  2. Sparano JA, Lee S, Chen MG, et al.: Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Trial (E1494). J Clin Oncol 22 (8): 1491-500, 2004.

  3. Ratner L, Lee J, Tang S, et al.: Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 19 (8): 2171-8, 2001.

  4. Levine AM, Tulpule A, Espina B, et al.: Liposome-encapsulated doxorubicin in combination with standard agents (cyclophosphamide, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma: results of therapy and correlates of response. J Clin Oncol 22 (13): 2662-70, 2004.

  5. Gill PS, Levine AM, Krailo M, et al.: AIDS-related malignant lymphoma: results of prospective treatment trials. J Clin Oncol 5 (9): 1322-8, 1987.

  6. Cingolani A, Gastaldi R, Fassone L, et al.: Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin's lymphomas. J Clin Oncol 18 (19): 3325-30, 2000.

  7. Scadden DT: Epstein-Barr virus, the CNS, and AIDS-related lymphomas: as close as flame to smoke. J Clin Oncol 18 (19): 3323-4, 2000.

  8. Palella FJ Jr, Delaney KM, Moorman AC, et al.: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338 (13): 853-60, 1998.

  9. Antinori A, Cingolani A, Alba L, et al.: Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS 15 (12): 1483-91, 2001.

  10. Hoffmann C, Wolf E, Fätkenheuer G, et al.: Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma. AIDS 17 (10): 1521-9, 2003.

  11. Tam HK, Zhang ZF, Jacobson LP, et al.: Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer 98 (6): 916-22, 2002.

  12. Vaccher E, Spina M, Talamini R, et al.: Improvement of systemic human immunodeficiency virus-related non-Hodgkin lymphoma outcome in the era of highly active antiretroviral therapy. Clin Infect Dis 37 (11): 1556-64, 2003.

  13. Mounier N, Spina M, Gabarre J, et al.: AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy. Blood 107 (10): 3832-40, 2006.

  14. Weiss R, Mitrou P, Arasteh K, et al.: Acquired immunodeficiency syndrome-related lymphoma: simultaneous treatment with combined cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and highly active antiretroviral therapy is safe and improves survival--results of the German Multicenter Trial. Cancer 106 (7): 1560-8, 2006.

  15. Wang ES, Straus DJ, Teruya-Feldstein J, et al.: Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer 98 (6): 1196-205, 2003.

  16. Cortes J, Thomas D, Rios A, et al.: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Cancer 94 (5): 1492-9, 2002.

  17. Lim ST, Karim R, Nathwani BN, et al.: AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy. J Clin Oncol 23 (19): 4430-8, 2005.

  18. Kaplan LD, Lee JY, Ambinder RF, et al.: Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood 106 (5): 1538-43, 2005.

  19. Martí-Carvajal AJ, Cardona AF, Lawrence A: Interventions for previously untreated patients with AIDS-associated non-Hodgkin's lymphoma. Cochrane Database Syst Rev (3): CD005419, 2009.

  20. Re A, Michieli M, Casari S, et al.: High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors. Blood 114 (7): 1306-13, 2009.

  21. Krishnan A, Molina A, Zaia J, et al.: Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 105 (2): 874-8, 2005.

  22. Costello RT, Zerazhi H, Charbonnier A, et al.: Intensive sequential chemotherapy with hematopoietic growth factor support for non-Hodgkin lymphoma in patients infected with the human immunodeficiency virus. Cancer 100 (4): 667-76, 2004.

  23. Balsalobre P, Díez-Martín JL, Re A, et al.: Autologous stem-cell transplantation in patients with HIV-related lymphoma. J Clin Oncol 27 (13): 2192-8, 2009.

AIDS-Related Primary Central Nervous System Lymphoma

Until the 1980s, primary central nervous system lymphoma (PCNSL) was a rare disease. PCNSL has increased dramatically in association with AIDS.[1] PCNSL accounts for approximately 0.6% of initial AIDS diagnoses and is the second most frequent central nervous system (CNS) mass lesion in adults with AIDS. As with other AIDS-related lymphomas, these are usually aggressive B-cell neoplasms, either diffuse large cell or diffuse immunoblastic non-Hodgkin lymphoma. Unlike AIDS-related systemic lymphomas, in which 30% to 50% of tumors are associated with Epstein-Barr virus (EBV), AIDS-related PCNSL has been reported to have a 100% association with EBV.[2] This percentage indicates a pathogenetic role for EBV in this disease. These patients usually have evidence of far-advanced AIDS, are severely debilitated, and present with focal neurologic symptoms such as seizures, changes in mental status, and paralysis.

Computed tomographic scans show contrast-enhancing mass lesions that may not always be distinguished from other CNS diseases, such as toxoplasmosis, that occur in AIDS patients.[3] Magnetic resonance imaging studies using gadolinium contrast may be a more useful initial diagnostic tool in differentiating lymphoma from cerebral toxoplasmosis or progressive multifocal leukoencephalopathy. Lymphoma tends to present with large lesions, which are enhanced by gadolinium. In cerebral toxoplasmosis, ring enhancement is very common, lesions tend to be smaller, and multiple lesions are seen.[4][5][6] Use of positron emission scanning has demonstrated an improved ability to distinguish PCNSL from toxoplasmosis.[7][8]

PSNCL has an increased uptake while toxoplasmosis lesions are metabolically inactive. Antibodies against toxoplasmosis may also be very useful because the vast majority of cerebral toxoplasmosis occur as a consequence of reactivity of a previous infection. If the IgG titer is less than 1:4, the disease is unlikely to be toxoplasmotic. A lumbar puncture may be useful to detect as many as 23% of patients with malignant cells in their cerebrospinal fluid (CSF). Evaluating the CSF for EBV DNA may be a useful lymphoma-specific tool since EBV is present in all patients with PCNSL. Despite all of these evaluations, however, the majority of patients with PCNSL require a pathologic diagnosis.[9][10][11] Diagnosis is made by biopsy. Sometimes, a biopsy is attempted only after failure of antibiotics for toxoplasmosis, which will produce clinical and radiographic improvement within 1 to 3 weeks in patients with cerebral toxoplasmosis.[12] PCNSL is often identified as a terminal manifestation of AIDS or on postmortem examination.

Radiation therapy alone has usually been used in this group of patients. With doses in the 35 Gy to 40 Gy range, median duration of survival has been only 72 to 119 days.[3][13][14] Survival is longer in younger patients with better performance status and the absence of opportunistic infection.[15] Most patients respond to treatment by showing partial improvement in neurologic symptoms. Autopsies have revealed that these patients die of opportunistic infections as well as tumor progression. Treatment of these patients is also complicated by other AIDS-related CNS infections, including subacute AIDS encephalitis, cytomegalovirus encephalitis, and toxoplasmosis encephalitis. Spontaneous remissions have been reported after highly active antiretroviral therapy.[16]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with AIDS-related primary CNS lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Ziegler JL, Beckstead JA, Volberding PA, et al.: Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 311 (9): 565-70, 1984.

  2. MacMahon EM, Glass JD, Hayward SD, et al.: Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet 338 (8773): 969-73, 1991.

  3. Goldstein JD, Dickson DW, Moser FG, et al.: Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation. Cancer 67 (11): 2756-65, 1991.

  4. Nyberg DA, Federle MP: AIDS-related Kaposi sarcoma and lymphomas. Semin Roentgenol 22 (1): 54-65, 1987.

  5. Fine HA, Mayer RJ: Primary central nervous system lymphoma. Ann Intern Med 119 (11): 1093-104, 1993.

  6. Ciricillo SF, Rosenblum ML: Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients. J Neurosurg 73 (5): 720-4, 1990.

  7. Hoffman JM, Waskin HA, Schifter T, et al.: FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS. J Nucl Med 34 (4): 567-75, 1993.

  8. Pierce MA, Johnson MD, Maciunas RJ, et al.: Evaluating contrast-enhancing brain lesions in patients with AIDS by using positron emission tomography. Ann Intern Med 123 (8): 594-8, 1995.

  9. Cinque P, Brytting M, Vago L, et al.: Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 342 (8868): 398-401, 1993.

  10. Cingolani A, De Luca A, Larocca LM, et al.: Minimally invasive diagnosis of acquired immunodeficiency syndrome-related primary central nervous system lymphoma. J Natl Cancer Inst 90 (5): 364-9, 1998.

  11. Yarchoan R, Jaffe ES, Little R: Diagnosing central nervous system lymphoma in the setting of AIDS: a step forward. J Natl Cancer Inst 90 (5): 346-7, 1998.

  12. Mathews C, Barba D, Fullerton SC: Early biopsy versus empiric treatment with delayed biopsy of non-responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis. AIDS 9 (11): 1243-50, 1995.

  13. Baumgartner JE, Rachlin JR, Beckstead JH, et al.: Primary central nervous system lymphomas: natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome. J Neurosurg 73 (2): 206-11, 1990.

  14. Remick SC, Diamond C, Migliozzi JA, et al.: Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature. Medicine (Baltimore) 69 (6): 345-60, 1990.

  15. Corn BW, Donahue BR, Rosenstock JG, et al.: Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: a multivariate analysis of a multi-institutional experience. Cancer J Sci Am 3 (1): 52-6, 1997 Jan-Feb.

  16. McGowan JP, Shah S: Long-term remission of AIDS-related primary central nervous system lymphoma associated with highly active antiretroviral therapy. AIDS 12 (8): 952-4, 1998.


This information is provided by the National Cancer Institute.

This information was last updated on November 19, 2013.


 
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