- General Information About Adult Non-Hodgkin Lymphoma
- Stages of Adult Non-Hodgkin Lymphoma
- Recurrent Adult Non-Hodgkin Lymphoma
- Treatment Option Overview
- Treatment Options for Indolent Non-Hodgkin Lymphoma
- Treatment Options for Aggressive Non-Hodgkin Lymphoma
- Treatment Options for Lymphoblastic Lymphoma
- Treatment Options for Burkitt Lymphoma
- Treatment Options for Recurrent Non-Hodgkin Lymphoma
- Treatment Options for Non-Hodgkin Lymphoma During Pregnancy
- To Learn More About Adult Non-Hodgkin Lymphoma
- About This PDQ Summary
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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
General Information About Adult Non-Hodgkin Lymphoma
Adult non-Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system.
Non-Hodgkin lymphoma is a type of cancer that forms in 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 infection and the growth of tumors. There are three types of lymphocytes:
- B lymphocytes that make antibodies to help fight infection. Also called B cells. Most types of non-Hodgkin lymphoma begin in B lymphocytes.
- T lymphocytes that help B lymphocytes make the antibodies that help fight infection. Also called T cells.
- Natural killer cells that attack cancer cells and viruses. Also called NK cells.
Non-Hodgkin lymphoma can begin in B lymphocytes, T lymphocytes, or natural killer cells. Lymphocytes can also be found in the blood and also collect in the lymph nodes, spleen, and thymus.
- 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. It 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.
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.
Lymph tissue is also found in other parts of the body such as the stomach, thyroid gland, brain, and skin. Cancer can spread to the liver and lungs.
Non-Hodgkin lymphoma during pregnancy is rare. Non-Hodgkin lymphoma in pregnant women is the same as the disease in nonpregnant women of childbearing age. However, treatment is different for pregnant women. This summary includes information on the treatment of non-Hodgkin lymphoma during pregnancy (see the Treatment Options for Non-Hodgkin Lymphoma During Pregnancy section for more information).
Non-Hodgkin lymphoma can occur in both adults and children. Treatment for adults is different than treatment for children. (See the PDQ summary on Childhood Non-Hodgkin Lymphoma Treatment for more information.)
The major types of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma.
Lymphomas are divided into two general types: Hodgkin lymphoma and non-Hodgkin lymphoma. This summary is about the treatment of adult non-Hodgkin lymphoma.
For information about certain types of lymphoma, see the following PDQ summaries:
- Adult Acute Lymphoblastic Leukemia Treatment (lymphoblastic lymphoma)
- Adult Hodgkin Lymphoma Treatment
- AIDS-Related Lymphoma Treatment
- Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma)
- Mycosis Fungoides and the Sézary Syndrome Treatment (cutaneous T-cell lymphoma)
- Primary CNS Lymphoma Treatment
Non-Hodgkin lymphoma can be indolent or aggressive.
Non-Hodgkin lymphoma grows and spreads at different rates and can be indolent or aggressive. Indolent lymphoma tends to grow and spread slowly, and has few signs and symptoms. Aggressive lymphoma grows and spreads quickly, and has signs and symptoms that can be severe. The treatments for indolent and aggressive lymphoma are different.
This summary is about the following types of non-Hodgkin lymphoma:
Indolent non-Hodgkin lymphomas
|Follicular lymphoma. Follicular lymphoma is the most common type of indolent non-Hodgkin lymphoma. It is a very slow-growing type of non-Hodgkin lymphoma that begins in B lymphocytes. It affects the lymph nodes and may spread to the bone marrow or spleen. Most patients with follicular lymphoma are age 50 years and older when they are diagnosed. Follicular lymphoma may go away without treatment. The patient is closely watched for signs or symptoms that the disease has come back. Treatment is needed if signs or symptoms occur after the cancer disappeared or after initial cancer treatment. Sometimes follicular lymphoma can become a more aggressive type of lymphoma, such as diffuse large B-cell lymphoma.|
|Lymphoplasmacytic lymphoma. In most cases of lymphoplasmacytic lymphoma, B lymphocytes that are turning into plasma cells make large amounts of a protein called monoclonal immunoglobulin M (IgM) antibody. High levels of IgM antibody in the blood cause the blood plasma to thicken. This may cause signs or symptoms such as trouble seeing or hearing, heart problems, shortness of breath, headache, dizziness, and numbness or tingling of the hands and feet. Sometimes there are no signs or symptoms of lymphoplasmacytic lymphoma. It may be found when a blood test is done for another reason. Lymphoplasmacytic lymphoma often spreads to the bone marrow, lymph nodes, and spleen. It is also called Waldenström macroglobulinemia.|
Marginal zone lymphoma. This type of non-Hodgkin lymphoma begins in B lymphocytes in a part of lymph tissue called the marginal zone. There are five different types of marginal zone lymphoma. They are grouped by the type of tissue where the lymphoma formed:
|Primary cutaneous anaplastic large cell lymphoma. This type of non-Hodgkin lymphoma is in the skin only. It can be a benign (not cancer) nodule that may go away on its own or it can spread to many places on the skin and need treatment.|
Aggressive non-Hodgkin lymphomas
Diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. It grows quickly in the lymph nodes and often the spleen, liver, bone marrow, or other organs are also affected. Signs and symptoms of diffuse large B-cell lymphoma may include fever, recurring night sweats, and weight loss. These are also called B symptoms.
Primary mediastinal large B-cell lymphoma is a type of diffuse large B-cell lymphoma.
|Follicular large cell lymphoma, stage III. Follicular large cell lymphoma, stage III, is a very rare type of non-Hodgkin lymphoma. It is more like diffuse large B-cell lymphoma than other types of follicular lymphoma.|
Anaplastic large cell lymphoma. Anaplastic large cell lymphoma is a type of non-Hodgkin lymphoma that usually begins in T lymphocytes. The cancer cells also have a marker called CD30 on the surface of the cell.
There are two types of anaplastic large cell lymphoma:
|Extranodal NK -/T-cell lymphoma. Extranodal NK-/T-cell lymphoma usually begins in the area around the nose. It may also affect the paranasal sinus (hollow spaces in the bones around the nose), roof of the mouth, trachea, skin, stomach, and intestines. Most cases of extranodal NK-/T-cell lymphoma have Epstein-Barr virus in the tumor cells. Sometimes hemophagocytic syndrome occurs (a serious condition in which there are too many active histiocytes and T cells that cause severe inflammation in the body). Treatment to suppress the immune system is needed. This type of non-Hodgkin lymphoma is not common in the United States.|
|Lymphomatoid granulomatosis. Lymphomatoid granulomatosis mostly affects the lungs. It may also affect the paranasal sinuses (hollow spaces in the bones around the nose), skin, kidneys, and central nervous system. In lymphomatoid granulomatosis, cancer invades the blood vessels and kills tissue. Because the cancer may spread to the brain, intrathecal chemotherapy or radiation therapy to the brain is given.|
|Angioimmunoblastic T-cell lymphoma. This type of non-Hodgkin lymphoma begins in T cells. Swollen lymph nodes are a common sign. Other signs may include a skin rash, fever, weight loss, or night sweats. There may also be high levels of gamma globulin (antibodies) in the blood. Patients may also have opportunistic infections because their immune systems are weakened.|
Peripheral T-cell lymphoma. Peripheral T-cell lymphoma begins in mature T lymphocytes. This type of T lymphocyte matures in the thymus gland and travels to other lymphatic sites in the body such as the lymph nodes, bone marrow, and spleen. There are three subtypes of peripheral T-cell lymphoma:
|Intravascular large B-cell lymphoma. This type of non-Hodgkin lymphoma affects blood vessels, especially the small blood vessels in the brain, kidney, lung, and skin. Signs and symptoms of intravascular large B-cell lymphoma are caused by blocked blood vessels. It is also called intravascular lymphomatosis.|
|Burkitt lymphoma. Burkitt lymphoma is a type of B-cell non-Hodgkin lymphoma that grows and spreads very quickly. It may affect the jaw, bones of the face, bowel, kidneys, ovaries, or other organs. There are three main types of Burkitt lymphoma (endemic, sporadic, and immunodeficiency related). Endemic Burkitt lymphoma commonly occurs in Africa and is linked to the Epstein-Barr virus, and sporadic Burkitt lymphoma occurs throughout the world. Immunodeficiency-related Burkitt lymphoma is most often seen in patients who have AIDS. Burkitt lymphoma may spread to the brain and spinal cord and treatment to prevent its spread may be given. Burkitt lymphoma occurs most often in children and young adults (See the PDQ summary on Childhood Non-Hodgkin Lymphoma Treatment for more information.) Burkitt lymphoma is also called diffuse small noncleaved-cell lymphoma.|
|Lymphoblastic lymphoma. Lymphoblastic lymphoma may begin in T cells or B cells, but it usually begins in T cells. In this type of non-Hodgkin lymphoma, there are too many lymphoblasts (immature white blood cells) in the lymph nodes and the thymus gland. These lymphoblasts may spread to other places in the body, such as the bone marrow, brain, and spinal cord. Lymphoblastic lymphoma is most common in teenagers and young adults. It is a lot like acute lymphoblastic leukemia (lymphoblasts are mostly found in the bone marrow and blood). (See the PDQ summary on Adult Acute Lymphoblastic Leukemia Treatment for more information.)|
|Adult T-cell leukemia/lymphoma. Adult T-cell leukemia/lymphoma is caused by the human T-cell leukemia virus type 1 (HTLV-1). Signs include bone and skin lesions, high blood calcium levels, and lymph nodes, spleen, and liver that are larger than normal.|
|Mantle cell lymphoma. Mantle cell lymphoma is a type of B-cell non-Hodgkin lymphoma that usually occurs in middle-aged or older adults. It begins in the lymph nodes and spreads to the spleen, bone marrow, blood, and sometimes the esophagus, stomach, and intestines. Patients with mantle cell lymphoma have too much of a protein called cyclin-D1 or a certain gene change in the lymphoma cells. In some patients who do not have signs or symptoms of lymphoma delaying the start of treatment does not affect the prognosis.|
|Posttransplantation lymphoproliferative disorder. This disease occurs in patients who have had a heart, lung, liver, kidney, or pancreas transplant and need lifelong immunosuppressive therapy. Most posttransplant lymphoproliferative disorders affect the B cells and have Epstein-Barr virus in the cells. Lymphoproliferative disorders are often treated like cancer.|
|True histiocytic lymphoma. This is a rare, very aggressive type of lymphoma. It is not known whether it begins in B cells or T cells. It does not respond well to treatment with standard chemotherapy.|
|Primary effusion lymphoma. Primary effusion lymphoma begins in B cells that are found in an area where there is a large build-up of fluid, such as the areas between the lining of the lung and chest wall (pleural effusion), the sac around the heart and the heart (pericardial effusion), or in the abdominal cavity. There is usually no tumor that can be seen. This type of lymphoma often occurs in patients who have AIDS.|
|Plasmablastic lymphoma. Plasmablastic lymphoma is a type of large B-cell non-Hodgkin lymphoma that is very aggressive. It is most often seen in patients with HIV infection.|
Age, gender, and a weakened immune system can affect the risk of adult non-Hodgkin lymphoma.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk.
These and other risk factors may increase the risk of certain types of adult non-Hodgkin lymphoma:
- Being older, male, or white.
- Having one of the following medical conditions:
- An inherited immune disorder (such as hypogammaglobulinemia or Wiskott-Aldrich syndrome).
- An autoimmune disease (such as rheumatoid arthritis, psoriasis, or Sjögren syndrome).
- Human T-lymphotrophic virus type I or Epstein-Barr virus infection.
- Helicobacter pylori infection.
- Taking immunosuppressant drugs after an organ transplant.
Signs and symptoms of adult non-Hodgkin lymphoma include swelling in the lymph nodes, fever, night sweats, weight loss, and fatigue.
These signs and symptoms may be caused by adult non-Hodgkin lymphoma or by other conditions. Check with your doctor if you have any of the following:
- Swelling in the lymph nodes in the neck, underarm, groin, or stomach.
- Fever for no known reason.
- Recurring night sweats.
- Feeling very tired.
- Weight loss for no known reason.
- Skin rash or itchy skin.
- Pain in the chest, abdomen, or bones for no known reason.
When fever, night sweats, and weight loss occur together, this group of symptoms is called B symptoms.
Other signs and symptoms of adult non-Hodgkin lymphoma may occur and depend on the following:
- Where the cancer forms in the body.
- The size of the tumor.
- How fast the tumor grows.
Tests that examine the body and lymph system are used to help detect (find) and diagnose adult non-Hodgkin 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.
- Flow cytometry: A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light. This test is used to diagnose lymphoplasmacytic lymphoma.
Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a needle into the hipbone or breastbone. A pathologist views the bone marrow and bone under a microscope to look for signs of cancer.
Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the patient's hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
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 part of a lymph node using a wide needle.
- Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle.
- Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to take tissue samples to be checked under a microscope for signs of disease.
- Laparotomy: A surgical procedure in which an incision (cut) is made in the wall of the abdomen to check the inside of the abdomen for signs of disease. Tissue samples are taken and checked under a microscope for signs of disease.
If cancer is found, the following tests may be done to study the cancer cells:
- Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer.
- Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.
- FISH (fluorescence in situ hybridization): A laboratory test used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA attach to certain genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light. This type of test is used to look for certain genetic markers.
- Immunophenotyping: A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose specific types of leukemia and lymphoma by comparing the cancer cells to normal cells of the immune system.
Other tests and procedures may be done depending on the signs and symptoms seen and where the cancer forms in 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 type of non-Hodgkin lymphoma.
- The amount of lactate dehydrogenase (LDH) in the blood.
- Whether there are certain changes in the genes.
- The patient's age and general health.
- Whether the lymphoma has just been diagnosed or has recurred (come back).
For non-Hodgkin lymphoma during pregnancy, the treatment options also depend on:
- The wishes of the patient.
- Which trimester of pregnancy the patient is in.
- Whether the baby can be delivered early.
Some types of non-Hodgkin lymphoma spread more quickly than others do. Most non-Hodgkin lymphomas that occur during pregnancy are aggressive. Delaying treatment of aggressive lymphoma until after the baby is born may lessen the mother's chance of survival. Immediate treatment is often recommended, even during pregnancy.
Stages of Adult Non-Hodgkin Lymphoma
After adult non-Hodgkin 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 the type of cancer and 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 of the disease in order to plan treatment. The results of the tests and procedures done to diagnose non-Hodgkin lymphoma are used to help make decisions about treatment.
The following tests and procedures may also be used in the staging process:
Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:
- The number of red blood cells and platelets.
- The number and type of white blood cells.
- The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
- The portion of the blood sample made up of 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.
- 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.
- 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): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
- Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a needle into the hipbone or breastbone. A pathologist views the bone marrow and bone under a microscope to look for signs of cancer.
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. This procedure is also called an LP or spinal tap.
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.
For pregnant women with non-Hodgkin lymphoma, staging tests and procedures that protect the baby from the harms of radiation are used. These tests and procedures include MRI, bone marrow aspiration and biopsy, lumbar puncture, and ultrasound. An ultrasound exam is a procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.
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 adult non-Hodgkin lymphoma may include E and S.
Adult non-Hodgkin 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 adult non-Hodgkin lymphoma:
Stage I adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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 adult non-Hodgkin 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).
Adult non-Hodgkin lymphomas may be grouped for treatment according to whether the cancer is indolent or aggressive and whether affected lymph nodes are next to each other in the body.
See the General Information section for more information on the types of indolent (slow-growing) and aggressive (fast-growing) non-Hodgkin lymphoma.
Non-Hodgkin lymphoma can also be described as contiguous or noncontiguous:
- Contiguous lymphomas: Lymphomas in which the lymph nodes with cancer are next to each other.
- Noncontiguous lymphomas: Lymphomas in which the lymph nodes with cancer are not next to each other, but are on the same side of the diaphragm.
Recurrent Adult Non-Hodgkin Lymphoma
Recurrent adult non-Hodgkin lymphoma is cancer that has recurred (come back) after it has been treated. The lymphoma may come back in the lymph system or in other parts of the body. Indolent lymphoma may come back as aggressive lymphoma. Aggressive lymphoma may come back as indolent lymphoma.
Treatment Option Overview
There are different types of treatment for patients with non-Hodgkin lymphoma.
Different types of treatment are available for patients with non-Hodgkin 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.
For pregnant women with non-Hodgkin lymphoma, treatment is carefully chosen to protect the baby. Treatment decisions are based on the mother's wishes, the stage of the non-Hodgkin lymphoma, and the age of the baby. The treatment plan may change as the signs and symptoms, cancer, and pregnancy change. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.
Patients with non-Hodgkin lymphoma should have their treatment planned by a team of health care providers who are experts in treating lymphomas.
Treatment will be overseen by a medical oncologist, a doctor who specializes in treating cancer, or a hematologist, a doctor who specializes in treating blood cancers. The medical oncologist may refer you to other health care providers who have experience and are experts in treating adult non-Hodgkin lymphoma and who specialize in certain areas of medicine. These may include the following specialists:
- Radiation oncologist.
- Rehabilitation specialist.
- Other oncology specialists.
Patients may develop late effects that appear months or years after their treatment for non-Hodgkin lymphoma.
Side effects from cancer treatment that begin during or after treatment and continue for months or years are called late effects. Treatment with chemotherapy, radiation therapy, or stem cell transplant for non-Hodgkin lymphoma may increase the risk of late effects.
Late effects of cancer treatment may include the following:
- Heart problems.
- Infertility (inability to have children).
- Loss of bone density.
- Neuropathy (nerve damage that causes numbness or trouble walking).
- A second cancer, such as:
- Lung cancer.
- Brain cancer.
- Kidney cancer.
- Bladder cancer.
- Hodgkin lymphoma.
- Myelodysplastic syndrome.
- Acute myeloid leukemia.
Some late effects may be treated or controlled. It is important to talk with your doctor about the effects cancer treatment can have on you. Regular follow-up to check for late effects is important.
Nine types of standard treatment are used:
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.
Total-body irradiation is a type of external radiation therapy that is given to the entire body. It may be given before a stem cell transplant.
The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used to treat adult non-Hodgkin lymphoma, and may also be used as palliative therapy to relieve symptoms and improve quality of life.
For pregnant women with non-Hodgkin lymphoma, radiation therapy should be given after delivery, if possible, to avoid any risk to the baby. If treatment is needed right away, pregnant women may decide to continue the pregnancy and receive radiation therapy. However, lead used to shield the baby may not protect it from scattered radiation that could possibly cause cancer in the future.
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 two or more anticancer drugs. Steroid drugs may be added, to lessen inflammation and lower the body's immune response.
The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Intrathecal chemotherapy may also be used in the treatment of lymphoma that first forms in the testicles or sinuses (hollow areas) around the nose, diffuse large B-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and some aggressive T-cell lymphomas. It is given to lessen the chance that lymphoma cells will spread to the brain and spinal cord. This is called CNS prophylaxis.
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.
In pregnant women, the baby is exposed to chemotherapy when the mother is treated, and some anticancer drugs cause birth defects. Because anticancer drugs are passed to the baby through the mother, both must be watched closely when chemotherapy is given.
See Drugs Approved for Non-Hodgkin Lymphoma for more information.
Immunotherapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer.
Immunomodulators are a type of immunotherapy. Lenalidomide is an immunomodulator used to treat adult non-Hodgkin lymphoma.
See Drugs Approved for Non-Hodgkin Lymphoma for more information.
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, proteasome inhibitor therapy, and kinase inhibitor therapy are types of targeted therapy used to treat adult non-Hodgkin 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. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Rituximab is a monoclonal antibody used to treat many types of non-Hodgkin lymphoma. Monoclonal antibodies that have been joined to radioactive material are called radiolabeled monoclonal antibodies. Yttrium-90-labeled ibritumomab tiuxetan is an example of a radiolabeled monoclonal antibody. Monoclonal antibodies are given by infusion.
Proteasome inhibitor therapy blocks the action of proteasomes in cancer cells and may prevent the growth of tumors.
Kinase inhibitor therapy, such as idelalisib, blocks certain proteins, which may help keep lymphoma cells from growing and may kill them. It is used to treat indolent lymphoma. Ibrutinib, a type of Bruton's tyrosine kinase inhibitor therapy, is used to treat lymphoplasmacytic lymphoma and mantle cell lymphoma.
See Drugs Approved for Non-Hodgkin Lymphoma for more information.
If the blood becomes thick with extra antibody proteins and affects circulation, plasmapheresis is done to remove extra plasma and antibody proteins from the blood. In this procedure, blood is removed from the patient and sent through a machine that separates the plasma (the liquid part of the blood) from the blood cells. The patient's plasma contains the unneeded antibodies and is not returned to the patient. The normal blood cells are returned to the bloodstream along with donated plasma or a plasma replacement. Plasmapheresis does not keep new antibodies from forming.
Watchful waiting is closely monitoring a patient's condition without giving any treatment until signs or symptoms appear or change.
Antibiotic therapy is a treatment that uses drugs to treat infections and cancer caused by bacteria and other microorganisms.
See Drugs Approved for Non-Hodgkin Lymphoma for more information.
Surgery may be used to remove the lymphoma in certain patients with indolent or aggressive non-Hodgkin lymphoma.
The type of surgery used depends on where the lymphoma formed in the body:
- Local excision for certain patients with mucosa-associated lymphoid tissue (MALT) lymphoma, PTLD, and small bowel T-cell lymphoma.
- Splenectomy for patients with marginal zone lymphoma of the spleen.
Patients who have a heart, lung, liver, kidney, or pancreas transplant usually need to take drugs to suppress their immune system for the rest of their lives. Long-term immunosuppression after an organ transplant can cause a certain type of non-Hodgkin lymphoma called post-transplant lymphoproliferative disorder (PLTD).
Small bowel surgery is often needed to diagnose celiac disease in adults who develop a type of T-cell lymphoma.
Stem cell transplant
Stem cell transplant is a method of giving high doses of chemotherapy and/or total-body irradiation and then 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 (autologous transplant) or a donor (allogeneic transplant) and are frozen and stored. After the chemotherapy and/or radiation therapy 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. (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. (Step 2): The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown). (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 website.
Vaccine therapy is a type of biologic therapy. Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy. Vaccine therapy can also be a type of targeted therapy.
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.
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 Indolent Non-Hodgkin Lymphoma
Treatment of indolent, stage I and contiguous stage II adult non-Hodgkin lymphoma may include the following:
- Radiation therapy.
- Monoclonal antibody therapy and/or chemotherapy.
- Watchful waiting.
If the tumor is too large to be treated with radiation therapy, the treatment options for indolent, noncontiguous stage II, III, or IV adult non-Hodgkin lymphoma will be used.
Treatment of indolent, noncontiguous stage II, III, or IV adult non-Hodgkin lymphoma may include the following:
- Watchful waiting for patients who do not have signs or symptoms.
- Monoclonal antibody therapy with or without chemotherapy.
- Chemotherapy with or without steroids.
- Combination chemotherapy.
- Kinase inhibitor therapy.
- Radiolabeled monoclonal antibody therapy.
- Monoclonal antibody therapy after treatment with combination chemotherapy.
- A clinical trial of high-dose chemotherapy with or without total-body irradiation or radiolabeled monoclonal antibody therapy, followed by autologous or allogeneic stem cell transplant.
- A clinical trial of chemotherapy with or without vaccine therapy.
- A clinical trial of new types of monoclonal antibodies.
- A clinical trial of radiation therapy that includes nearby lymph nodes, for patients who have stage III disease.
- A clinical trial of low-dose radiation therapy, to relieve symptoms and improve quality of life.
After initial treatment with the monoclonal antibody rituximab with or without chemotherapy, more treatment with rituximab may be given.
Other treatments for indolent non-Hodgkin lymphoma depend on the type of non-Hodgkin lymphoma. Treatment may include the following:
- For follicular lymphoma, treatment may be within a clinical trial of new monoclonal antibody therapy, new chemotherapy regimen, or a stem cell transplant.
- For lymphoplasmacytic lymphoma, Bruton's tyrosine kinase inhibitor therapy and/or plasmapheresis (if needed to make the blood thinner) is used. Other treatments that are like those used for follicular lymphoma may also be given.
- For gastric mucosa-associated lymphoid tissue (MALT) lymphoma, antibiotic therapy to treat Helicobacter pyloriinfection is given first. For tumors that do not respond to antibiotic therapy, treatment is radiation therapy, surgery, or rituximab with or without chemotherapy.
- For extragastric MALT lymphoma of the eye and Mediterranean abdominal lymphoma, antibiotic therapy is used to treat infection.
- For splenic marginal zone lymphoma, rituximab with or without chemotherapy and B-cell receptor therapy is used as initial treatment. If the tumor does not respond to treatment, a splenectomy may be done.
Treatment Options for Aggressive Non-Hodgkin Lymphoma
Treatment of aggressive, stage I and contiguous stage II adult non-Hodgkin lymphoma may include the following:
- Monoclonal antibody therapy and combination chemotherapy. Sometimes radiation therapy is given later.
- A clinical trial of a new regimen of monoclonal antibody therapy and combination chemotherapy.
Treatment of aggressive, noncontiguous stage II, III, or IV adult non-Hodgkin lymphoma may include the following:
- Monoclonal antibody therapy with combination chemotherapy.
- Combination chemotherapy.
- A clinical trial of monoclonal antibody therapy with combination chemotherapy followed by radiation therapy.
Other treatments depend on the type of aggressive non-Hodgkin lymphoma. Treatment may include the following:
- For extranodal NK -/T-cell lymphoma, radiation therapy that may be followed by chemotherapy and CNS prophylaxis.
- For posttransplantation lymphoproliferative disorder, treatment with immunosuppressive drugs may be stopped. If this does not work or cannot be done, monoclonal antibody therapy alone or with chemotherapy may be given. For cancer that has not spread, surgery to remove the cancer or radiation therapy may be used.
- For plasmablastic lymphoma, treatments are like those used for lymphoblastic lymphoma or Burkitt lymphoma.
For information on the treatment of lymphoblastic lymphoma, see Treatment Options for Lymphoblastic Lymphoma and for information on the treatment of Burkitt lymphoma, see Treatment Options for Burkitt Lymphoma.
Treatment Options for Lymphoblastic Lymphoma
Treatment of adult lymphoblastic lymphoma may include the following:
- Combination chemotherapy and CNS prophylaxis. Sometimes radiation therapy is also given to shrink a large tumor.
- A clinical trial of stem cell transplant after initial treatment.
Treatment Options for Burkitt Lymphoma
Treatment of adult Burkitt lymphoma may include the following:
- Combination chemotherapy with or without monoclonal antibody therapy.
- CNS prophylaxis.
Treatment Options for Recurrent Non-Hodgkin Lymphoma
Treatment of indolent, recurrent adult non-Hodgkin lymphoma may include the following:
- Chemotherapy with one or more drugs.
- Monoclonal antibody therapy.
- Radiolabeled monoclonal antibody therapy.
- Radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
- A clinical trial of an autologous or allogeneic stem cell transplant.
Treatment of aggressive, recurrent adult non-Hodgkin lymphoma may include the following:
- Chemotherapy with or without stem cell transplant.
- Monoclonal antibody therapy with or without combination chemotherapy followed by autologous stem cell transplant.
- Radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
- Radiolabeled monoclonal antibody therapy.
- For mantle cell lymphoma, treatment may include the following:
- Bruton's tyrosine kinase inhibitor therapy.
- A clinical trial of lenalidomide with monoclonal antibody therapy.
- A clinical trial comparing lenalidomide to other therapy.
- A clinical trial of autologous or allogeneic stem cell transplant.
Treatment of indolent lymphoma that comes back as aggressive lymphoma depends on the type of non-Hodgkin lymphoma and may include radiation therapy as palliative therapy to relieve symptoms and improve quality of life. Treatment of aggressive lymphoma that comes back as indolent lymphoma may include chemotherapy.
Treatment Options for Non-Hodgkin Lymphoma During Pregnancy
Indolent Non-Hodgkin Lymphoma During Pregnancy
Women who have indolent (slow-growing) non-Hodgkin lymphoma during pregnancy may be treated with watchful waiting until after they give birth. (See the Treatment Options for Indolent Non-Hodgkin Lymphoma section for more information.)
Aggressive Non-Hodgkin Lymphoma During Pregnancy
Treatment of aggressive non-Hodgkin lymphoma during pregnancy may include the following:
- Treatment given right away based on the type of non-Hodgkin lymphoma to increase the mother's chance of survival. Treatment may include combination chemotherapy and rituximab.
- Early delivery of the baby followed by treatment based on the type of non-Hodgkin lymphoma.
- If in the first trimester of pregnancy, medical oncologists may advise ending the pregnancy so that treatment may begin. Treatment depends on the type of non-Hodgkin lymphoma.
To Learn More About Adult Non-Hodgkin Lymphoma
For more information from the National Cancer Institute about adult non-Hodgkin lymphoma, see the following:
- Non-Hodgkin Lymphoma Home Page
- What You Need to Know About™ Non-Hodgkin Lymphoma
- Drugs Approved for Non-Hodgkin Lymphoma
- Targeted Cancer Therapies
- Biological Therapies for Cancer
For general cancer information and other resources from the National Cancer Institute, see the following:
- Chemotherapy and You: Support for People With Cancer
- Radiation Therapy and You: Support for People With Cancer
- Coping with Cancer
- Questions to Ask Your Doctor about Cancer
- For Survivors and Caregivers
About This PDQ Summary
Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.
PDQ is a service of the NCI. The NCI is part of the National Institutes of Health (NIH). NIH is the federal government's center of biomedical research. The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH.
Purpose of This Summary
This PDQ cancer information summary has current information about the treatment of adult non-Hodgkin lymphoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.
Reviewers and Updates
Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change.
The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.
Clinical Trial Information
A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." 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.
Clinical trials are listed in PDQ and can be found online at NCI's website. Many cancer doctors who take part in clinical trials are also listed in PDQ. For more information, call the Cancer Information Service 1-800-4-CANCER (1-800-422-6237).
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The best way to cite this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Adult Non-Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389337]
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Last Revised: 2016-08-03
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