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Lymphoma - Non-Hodgkin - Overview

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find some basic information about this disease and the parts of the body it may affect. This is the first page of Cancer.Net’s Guide to Non-Hodgkin Lymphoma. To see other pages, use the menu on the side of your screen. Think of that menu as a roadmap to this full guide.

About the lymphatic system

The lymphatic system is made up of thin tubes and groups of tiny, bean-shaped organs called lymph nodes that are located throughout the body. The largest clusters of lymph nodes are found in the abdomen, groin, pelvis, underarms, and neck.

The lymphatic system carries lymph, a colorless fluid containing lymphocytes (a type of white blood cell). Lymphocytes are part of the immune system and help fight germs in the body. B-lymphocytes (also called B cells) make antibodies that fight bacteria, while T-lymphocytes (also called T cells) kill viruses and foreign cells and trigger the B cells to make antibodies. Natural killer cells (NK cells) also kill viruses and can directly kill cells infected by viruses.

Other parts of the lymphatic system include the spleen, which makes lymphocytes and filters the blood; the thymus, an organ under the breastbone; the tonsils, located in the throat; and the bone marrow, the spongy red tissue inside bones that makes white blood cells (cells that fight infection), red blood cells (cells that carry oxygen throughout the body), and platelets (cells that help the blood to clot).

About non-Hodgkin lymphoma

Lymphoma begins when B cells, T cells, or NK cells in the lymphatic system change and grow uncontrollably, which sometimes may form a tumor. Hodgkin lymphoma is a specific type of lymphoma that is covered in another section of this website. Non-Hodgkin lymphoma (NHL) is a term that refers to the many other types of cancer of the lymphatic system, which can have different symptoms and signs, physical findings, and treatments.

Because lymphatic tissue is found in most parts of the body, NHL can start almost anywhere and can spread to almost any organ. It most often begins in the lymph nodes, liver, spleen, or bone marrow, but it can also involve the stomach, intestines, skin, thyroid gland, brain, or any other part of the body.

It is very important to know which type and subtype has been diagnosed because this information helps doctors determine the best treatment and a patient’s prognosis (chance of recovery). More specific information can be found in the Subtypes of NHL section of this guide.

This guide covers NHL in adults. Learn more about childhood NHL.

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If you would like additional introductory information, explore these related items. Please note these links take you to other sections on Cancer.Net:

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Lymphoma - Non-Hodgkin - Statistics

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find information about how many people learn they have this type of lymphoma each year and some general survival information. Remember, survival rates depend on several factors. To see other pages, use the menu on the side of your screen.

This year, an estimated 70,800 people (38,270 men and 32,530 women) in the United States will be diagnosed with NHL. While some subtypes of NHL are common in children, NHL is more common in adults overall. NHL is the sixth most common cancer in women and the seventh most common cancer in men.

It is estimated that 18,990 deaths (10,470 men and 8,520 women) from this disease will occur this year, making it the eighth most common cause of cancer death among women and the ninth most common cause of cancer death in men. The one-year relative survival rate is the percentage of people who survive at least one year after the cancer is detected, excluding those who die from other diseases. The one-year relative survival rate of patients with NHL is 81%. The five-year and 10-year relative survival rates are 69% and 58%, respectively, but vary depending on the subtype.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of people with different types and subtypes of lymphoma in the United States and may not apply to a single person or type of lymphoma. It is not possible to tell a person how long he or she will live with NHL. Because the survival statistics are often measured in multi-year intervals, they may not represent advances made in the treatment or diagnosis of this cancer. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2014.

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Lymphoma - Non-Hodgkin - Risk Factors

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find out more about what factors increase the chance of developing this type of lymphoma. To see other pages, use the menu on the side of your screen.

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The exact cause of NHL is not known, but the following factors may raise a person’s risk of developing NHL:

Age. The risk of NHL increases with age. The most common types occur most often in people in their 60s and 70s.

Gender. Men are more likely to develop NHL than women.

Bacterial infections. Some types of NHL are associated with specific infections. For example, MALT lymphoma of the stomach is thought to be caused by an infection with bacteria called Helicobacter pylori. If this lymphoma is diagnosed very early, it will sometimes go away if the infection is cured with antibiotics. Other types of MALT lymphoma, including those affecting the lungs, tear glands, and skin, may also be caused by infections.

Viruses. Viruses cause some types of NHL. For example, as explained in the Subtypes section, Epstein-Barr virus (EBV, the virus that causes mononucleosis, also known as "mono") is associated with some types of NHL, including Burkitt lymphoma and lymphomas occurring after an organ transplant. EBV may also cause some types of NHL in people between 60 and 90 years old. However, the virus is probably not the only factor, so people who have had mono do not necessarily have an increased risk of developing NHL in the future. In addition, hepatitis C infection has been associated with an increased risk of marginal zone lymphomas (see Subtypes). Other viruses have also been found to be important in causing other, rare types of lymphoma.

Immune deficiency disorders. Immune system disorders, such as HIV/AIDS, increase the risk of NHL, especially the aggressive B-cell lymphomas.

Autoimmune disorders. People with autoimmune disorders, such as rheumatoid arthritis and Sjögren syndrome, have an increased risk of developing certain types of NHL. Also, some drugs used to treat autoimmune disorders may increase the risk of NHL.

Organ transplantation. Organ transplant recipients have a higher risk of NHL because of the drugs that must be taken to lower immune system function to protect the transplanted organ.

Previous cancer treatment. Previous treatment with certain drugs for other types of cancer may increase the risk of NHL.

Chemical exposure. Exposure to certain chemicals, such as pesticides and petrochemicals, may increase the risk of NHL.

To continue reading this guide, use the menu on the side of your screen to select another section.  

Lymphoma - Non-Hodgkin - Symptoms and Signs

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. To see other pages, use the menu on the side of your screen.

People with NHL may experience a variety of symptoms. Many of these symptoms can also be caused by conditions other than lymphoma. There are very few symptoms that are specific to lymphoma, and this explains why it can sometimes be difficult to make a diagnosis. If you are concerned about a symptom on this list, please talk with your doctor.

The symptoms of NHL depend on where the cancer started and the organ that is involved.

General symptoms:

  • Enlarged lymph nodes in the abdomen, groin, neck, or underarms
  • Enlarged spleen or liver
  • Fever that cannot be explained by an infection or other illness
  • Weight loss with no known cause
  • Sweating and chills
  • Fatigue

Examples of symptoms related to a specific tumor location:

  • A tumor in the abdomen can cause a stretched belly or pain in the back or abdomen.
  • A tumor in the center of the chest may press on the trachea and cause chest pain, difficulty breathing, or other respiratory problems.

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you’ve been experiencing the symptom(s) and how often.

If lymphoma is diagnosed, your doctor may also use certain symptoms to help describe the disease, called staging. Each stage of NHL may be subdivided into "A" and "B" categories based on a person’s symptoms.

A means that a person has not experienced B symptoms, listed below.

B means that a person has experienced the following symptoms:

  • Unexplained weight loss of more than 10% of their original body weight during the six months before diagnosis
  • Unexplained fever with temperatures above 100.4º F (38º C)
  • Drenching night sweats. Most patients say that either their nightclothes or the sheets on the bed are actually wet. Sometimes, heavy sweating occurs during the day.

Once NHL has been diagnosed and staged, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

The next section helps explain what tests and scans may be needed to learn more about the cause of the symptoms. Use the menu on the side of your screen to select Diagnosis, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Diagnosis

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find a list of the common tests, procedures, and scans that doctors can use to find out what’s wrong and identify the cause of the problem. To see other pages, use the menu on the side of your screen.

Doctors use many tests to diagnose cancer and determine if it has spread. Some tests may also determine which treatments may be the most effective. A biopsy is the only way to make a definitive diagnosis of lymphoma. Imaging tests may be used to find out whether the lymphoma has spread. This list describes options for diagnosing this type of cancer, and not all tests listed will be used for every person. Your doctor may consider these factors when choosing a diagnostic test:

  • Age and medical condition
  • Type of lymphoma suspected
  • Signs and symptoms
  • Previous test results

To determine if a person has NHL, the doctor will first take a complete medical history and do a physical examination, paying special attention to the lymph nodes, liver, and spleen. The doctor will also look for signs of infection that may cause the lymph nodes to swell and may prescribe an antibiotic. If the swelling in the lymph nodes still does not go down after antibiotic treatment, the swelling may be caused by something other than an infection. If the doctor suspects lymphoma, he or she will recommend a biopsy, as well as laboratory and imaging tests.

The following tests may be used to diagnose and manage NHL:

Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. This tissue may be removed using a fine needle, a cutting needle, or surgery. To diagnose lymphoma, the most common places tissue is removed from during a biopsy are the lymph nodes in the neck, under an arm, or in the groin. A biopsy may also be taken from the chest or abdomen using a fine needle during a computed tomography (CT) scan (see below) or from the stomach or intestine during an endoscopy (a test that allows the doctor to see inside the body with a thin, lighted, flexible tube). A biopsy of the skin may also be needed depending on the suspected subtype of lymphoma.

A biopsy is the only way to make a definite diagnosis of lymphoma and find out the subtype. Having enough tissue is very important to make a diagnosis. Very rarely, needle biopsy samples are sufficient to make a definite diagnosis of lymphoma. In most cases, a core biopsy or surgical biopsy is needed to remove enough tissue to diagnose and classify the lymphoma correctly. The tissue sample removed during the biopsy should be analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) or a hematopathologist (a pathologist who has extra training in the diagnosis of blood cancers) who is experienced in the diagnosis of lymphoma. Because there are so many subtypes of lymphoma and because some of these subtypes are very uncommon or rare, getting a second opinion may be helpful.

Molecular testing. Your doctor may recommend running laboratory tests on the lymphoma cells to identify specific genes, proteins, chromosome changes, and other factors unique to the disease. Results of these tests will help decide on your treatment options. There are different types of molecular and genetic testing, including cytogenetics (a study of normal and abnormal chromosomes in dividing cancer cells), fluorescent in situ hybridization (FISH, using fluorescent probes under a special microscope to detect chromosomal abnormalities), flow cytometry (looking at proteins that are on the surface or inside a cancer cell), and polymerase chain reaction (PCR, used to detect specific DNA sequences that occur in some cancers).

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. A CT scan can also be used to measure the size of a tumor. Sometimes, a contrast medium (a special dye) is injected into a patient’s vein or given orally (by mouth) to provide better detail and find the exact position of a tumor. A radiologist (a doctor who specializes in performing imaging tests to diagnose disease) interprets CT scans. CT scans of the chest, abdomen, and pelvis can help find cancer that has spread to the lungs, lymph nodes, and liver.

Magnetic resonance imaging (MRI) scan. An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A contrast medium may be injected into a patient’s vein or given orally to create a clearer picture. A radiologist interprets the scan. 

Positron emission tomography (PET) scan. A PET scan is another imaging test that can help find cancer in the body. A small amount of a radioactive substance (called radioactive glucose) is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the substance. A scanner then detects this substance to produce images of the inside of the body. A nuclear medicine physician interprets the scan.

Integrated PET-CT scan. This scanning method collects images from both a CT and PET scan at the same time, and then combines the images. This technique can be used to look at both the structure and how much energy is used by the tumor and healthy tissues.

If after having one or more imaging tests the doctor decides the lymphoma might be affecting the bone marrow, he or she would recommend having a bone marrow biopsy.

Bone marrow biopsy and aspiration. These two procedures are often done at the same time. Bone marrow has both a solid and a liquid part. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. An aspiration removes a sample of fluid with a needle. The sample(s) are then analyzed by a pathologist. The most common site for a bone marrow biopsy and aspiration is the iliac crest of the pelvic bone, located in the lower back of the hip. The skin and bone in that area are numbed with medication beforehand, and other types of anesthesia (medication to block the awareness of pain) may be used.

Lymphoma often spreads to the bone marrow, so looking at a sample of the bone marrow can be important for doctors to diagnose lymphoma and determine the stage. The sample removed during the aspiration is also used to find any chromosome changes.

After these diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is cancer, these results also help the doctor describe the cancer; this is called staging.

The next section helps explain the different types and subtypes of NHL that may be diagnosed. Use the menu on the side of your screen to select Subtypes, or you can select another section, to continue reading this guide.

Lymphoma - Non-Hodgkin - Subtypes

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find descriptions of the most common types and subtypes of NHL, as well as information about how each may be treated. To see other pages, use the menu on the side of your screen.

There are different types and many subtypes of NHL, and it is very important to know which type and subtype has been diagnosed. Below are the most common types and subtypes, including information about how each may be treated. For more information about the treatment information described here, please read the Treatment Options section.

First, the doctor will determine what type of cell the lymphoma started in and classify the disease within three major groups:

B-cell lymphoma. About 90% of people with lymphoma have B-cell lymphoma.

T-cell lymphoma. About 10% of people with lymphoma have T-cell lymphoma.

NK-cell lymphoma. Less than 1% of people with lymphoma have NK-cell lymphoma.

NHL is also described by how quickly the cancer is growing: indolent or aggressive. Indolent and aggressive NHL are equally common in adults. In children, aggressive NHL is more common.

Indolent NHL. These types of lymphoma grow very slowly. As a result, people with indolent NHL may not need to start treatment when it is first diagnosed. They are followed closely, and treatment is only started when they develop symptoms or the disease begins to change; this is called watchful waiting. When indolent lymphoma is located only in one area (called localized disease, stages I and II; see the Stages section), radiation therapy may eliminate the NHL. However, most patients with this type of lymphoma have later-stage disease, stage III or IV, at the time of diagnosis. There are many effective treatments for these stages of indolent lymphoma, but it may come back months or years after treatment is complete, requiring additional treatment.

Aggressive NHL. These types of lymphoma may develop rapidly, and treatment is usually started immediately. These types of lymphoma usually need more intensive chemotherapy. Radiation treatment may be recommended in addition to chemotherapy, especially in patients with limited stage disease (stage I or II). Many forms of aggressive lymphoma may be cured with effective treatment.

Some subtypes of lymphoma cannot easily be classified as indolent or aggressive. For example, mantle cell lymphoma (see below) has features of both indolent and aggressive NHL.

Subtyping

In addition to determining if the NHL is indolent or aggressive and whether it is B-cell, T-cell, of NK-cell lymphoma, it is very important to determine the subtype of NHL because each subtype can behave differently and may require different treatments. There are about 35 subtypes of NHL. The most common subtypes are described below, along with some basic information about different treatments (learn more in the Treatment Options section).

Distinguishing between the different subtypes of NHL can be difficult and requires pathologists or hematopathologists who are experts in the diagnosis of lymphoma. Such specialists will use sophisticated techniques and work closely with experienced oncologists. The diagnosis is based on how the lymphoma looks under the microscope and confirmed by additional information from other tests, including tests of genetic material within the lymphoma cells. For more information on this process, see the Diagnosis section.

Subtypes of B-cell lymphoma

The most common subtypes of B-cell lymphoma are described below.

Diffuse large B-cell lymphoma (DLBCL). This is the most common form of lymphoma; about 30% of people in the United States with NHL have this type. It is an aggressive form of NHL that involves organs other than the lymph nodes about 40% of the time. DLBCL is often curable with chemotherapy given in combination with rituximab (Rituxan); see the Treatment Options section for more information. Radiation therapy is also used for some patients, especially if the lymphoma is localized (in a small area). Treatments to prevent the lymphoma from spreading to the brain, called central nervous system (CNS) prophylaxis, may be given, but most patients do not need this type of treatment. Recent research has shown that there are different types of DLBCL, known as germinal center and non-germinal center. Clinical trials (research studies) to find out whether different types of treatment should be used for these different types of DLBCL are ongoing.

Follicular lymphoma. This is the second most common form of lymphoma in the United States and Europe. About 20% of people with NHL have this type. It usually begins in the lymph nodes, is most often indolent, and grows very slowly. There is no known cure; however, recent studies show that about 80% of patients live for at least five years after being diagnosed with follicular lymphoma, and 50% are estimated to live longer than 12 years. Patients with follicular lymphoma may receive a combination of chemotherapy, monoclonal antibodies (a type of targeted therapy), and/or radiation therapy, or they may be followed closely with watchful waiting (see the Treatment Options section).

Recent clinical trials have suggested that the survival for patients with follicular lymphoma has improved over the last few years, although more research is needed to confirm this. Newer drugs such as bendamustine (Treanda) and lenalidomide (Revlimid) have been shown to be effective for this subtype and are being studied in clinical trials as part of first-line treatment (initial treatment given after diagnosis).

Over time, follicular lymphoma may turn into DLBCL (see above), which will then require more aggressive treatment. This is called transformation. Stem cell transplantation, tumor vaccines, and monoclonal antibody treatments may also be available in clinical trials.

Localized radiation therapy is often a common treatment choice for early-stage disease (stages I and II), but it may be combined with other treatments as well.

Mantle cell lymphoma. About 7% of people with NHL have mantle cell lymphoma. It most often appears in people older than 60 and is more common in men than women. It usually involves the bone marrow, lymph nodes, spleen, and gastrointestinal system (esophagus, stomach, intestines). Mantle cell lymphoma is usually identified by a protein called the cyclin D1 protein.

The initial approach to treating mantle cell lymphoma is to use a combination of chemotherapy drugs with rituximab. Because many people with mantle cell lymphoma will have the disease return after finishing chemotherapy, some patients may be offered high-dose chemotherapy followed by autologous stem cell transplantation at the end of their initial chemotherapy treatment. Patients who do not have a stem cell transplant may be offered maintenance therapy with monoclonal antibodies.  

When chemotherapy does not work, there are differing opinions on the best way to treat mantle cell lymphoma. Newer drugs such as bortezomib (Velcade), bendamustine, and lenalidomide have been shown to be effective for this subtype and are being studied in clinical trials as part of first-line treatment. Other new drugs are also being studied for mantle cell lymphoma. Some patients may have a slower growing form of the disease that may be managed like follicular lymphoma (see above).

Small lymphocytic lymphoma. This type of lymphoma is very closely related to a disease called B-cell chronic lymphocytic leukemia (CLL), and about 5% of people with NHL have this subtype. It is considered an indolent lymphoma. Patients with small lymphocytic lymphoma may receive a combination of chemotherapy, monoclonal antibodies, and/or radiation therapy, or they may be followed closely with watchful waiting. Stem cell transplantation, tumor vaccines, and monoclonal antibody treatments may also be available in clinical trials.

Mediastinal large B-cell lymphoma. This is an aggressive form of DLBCL (see above). It appears as a large mass in the chest area, which may cause breathing problems or superior vena cava syndrome (SVCS), a collection of symptoms caused by the partial blockage or compression of the superior vena cava, the major vein that carries blood from the head, neck, upper chest, and arms to the heart. Mediastinal large B-cell lymphoma is most common in women between 30 and 40 years old, and about 2.5% of people with NHL have this subtype. It is treated most often with anthracycline-based chemotherapy, and most patients also receive rituximab and radiation therapy to the chest. There are newer chemotherapy treatments that may eliminate the need for radiation therapy.

Splenic marginal zone B-cell lymphoma. This type of lymphoma begins in the spleen and can also involve the blood. It is usually slow growing, and the treatment approach is often watchful waiting. Sometimes, surgical removal of the spleen is recommended.

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). This type of lymphoma most commonly occurs in the stomach, but it may also occur in the lung, skin, thyroid, salivary gland, or eye. Patients with this type of lymphoma sometimes have a history of autoimmune disease, such as lupus, rheumatoid arthritis, or Sjögren’s syndrome. When MALT occurs in the stomach, it is often successfully treated with antibiotics to treat an infection with Helicobacter pylori bacteria, which is thought to cause the lymphoma. Other times, radiation therapy, surgery, chemotherapy, monoclonal antibodies, or a combination of these is the most common treatment plan. For disease in only one part of the body, radiation therapy can often cure the NHL.

Nodal marginal zone B-cell lymphoma. This type of indolent lymphoma involves the lymph nodes. It is rare; about 1% of people with lymphoma have this subtype. In general, this subtype of lymphoma is treated similarly to follicular lymphoma (see above).

Lymphoplasmacytic lymphoma. This is an indolent form of lymphoma, and 1% of people with NHL have this subtype. This form of lymphoma most often involves the bone marrow, lymph nodes, and spleen. In many patients, this lymphoma produces proteins (called an “M protein”) that are found at high levels in the blood. When this occurs, the condition is called Waldenstrom’s macroglobulinemia (WM). Patients with WM sometimes have thickened blood, which may cause symptoms such as headache, blurry vision, dizziness, and shortness of breath. Treatment is similar to chronic lymphocytic lymphoma/leukemia and may include watchful waiting, chemotherapy, monoclonal antibodies, or combinations of chemotherapy and monoclonal antibodies. Chemotherapy followed by stem cell transplantation is being studied in clinical trials.

Primary effusion lymphoma. This very aggressive form of lymphoma most often occurs in people who have the human immunodeficiency virus (HIV, the virus that causes autoimmune deficiency syndrome or AIDS), people whose immune system does not work well for other reasons, or people who are elderly. It begins in the lung, heart, or abdominal cavities; often, there is not one tumor. It is treated the same as other diffuse large cell lymphomas (see above).

Burkitt lymphoma/Burkitt cell leukemia. This is a very rare and aggressive form of lymphoma. There are three forms of Burkitt lymphoma: endemic, sporadic, and immunodeficiency-related lymphoma. It occurs most commonly in Africa, appears most often in the jawbones of children, and is usually associated with infection with EBV. It can also be associated with HIV. In the United States, Burkitt lymphoma appears most commonly with a mass in the abdomen. Because this type of lymphoma spreads quickly, it needs immediate treatment that includes intensive chemotherapy, usually with some treatment for the central nervous system to prevent it from spreading to the brain. This type of NHL is often curable with immediate treatment.

Subtypes of T-cell and natural killer (NK) lymphoma

The most common subtypes of T-cell and a cell called natural killer (NK; cells that fight microbes and cancer cells) lymphoma are described below.

Anaplastic large cell lymphoma, primary cutaneous type. This subtype of lymphoma only involves the skin. It is often indolent, although aggressive subtypes of the disease are possible. When the cancer is localized, radiation therapy is often effective. If it has spread, chemotherapy is the usual treatment. New drugs have recently been developed for the treatment of cutaneous lymphomas, some of which can be given orally (by mouth) as a pill.

Anaplastic large cell lymphoma, systemic type. This form makes up about 2% of all lymphomas and about 10% of all childhood lymphomas. An increased amount of the ALK-1 protein may be found in the cancer cells of this subtype for some people. Those who have this subtype of lymphoma with the ALK-1 protein in the cells often have a better prognosis (chance of recovery) than those who have this subtype without the ALK-1 protein in the cell. It is an aggressive form of lymphoma, but treatment often works well, including new treatments such as the monoclonal antibody brentuximab vendotin (Adcetris) (see the Treatment Options section).

Peripheral T-cell lymphoma, NOS. This is an aggressive form of lymphoma that is most often found when it is advanced. It is most common in people older than 60 and makes up about 6% of all lymphomas in the United States and Europe. The cells of this lymphoma are variable in size, and they have certain types of proteins (called CD4 or CD8) on their surface. It is treated with chemotherapy like DLBCL (see above) or other drugs. Many new drugs are also being studied in clinical trials. Stem cell transplantation may sometimes be an option.

Angioimmunoblastic T-cell lymphoma. This is an aggressive form of lymphoma with specific symptoms: swollen lymph nodes, fever, weight loss, rash, and high levels of antibodies called gamma globulin in the blood. Since patients with angioimmunoblastic lymphoma have lowered immune systems, infections are also common. This type of lymphoma is identified by what it looks like under a microscope and by certain proteins found in the tumor cells. It is treated like other diffuse large cell lymphomas.

Precursor T-lymphoblastic lymphoma/leukemia (precursor T-cell acute lymphoblastic leukemia). This is a rare type of lymphoma that makes up about 2% of all NHL. It is most common for young adults and is more common for men than women. This type of lymphoma is the same as a form of leukemia called acute lymphoblastic leukemia (ALL). When it is mainly located in the lymph nodes it is called lymphoblastic lymphoma, and when it is mainly found in the blood or bone marrow it is called ALL. When it is mainly in the lymph nodes, it most commonly involves the lymph nodes in the center of the chest. Both lymphoblastic lymphoma and ALL are aggressive diseases that require intensive chemotherapy, including treatment for the central nervous system to prevent it from spreading to the brain. Stem cell transplantation is sometimes used. It is often cured with these treatments.

Adult T-cell lymphoma/leukemia (human T-cell lymphotropic virus type I positive). This type of lymphoma is caused by a virus called the human T-cell lymphotropic virus type I. It is an aggressive disease that most often involves the bone and skin. Often, lymphoma cells are found in the blood, which is why this condition is sometimes also called leukemia. Chemotherapy does not usually work well for this form of lymphoma, although zidovudine (Retrovir) and interferon have helped some patients. About two-thirds of patients experience remission (temporary or permanent absence of cancer symptoms).

Extranodal NK/T-cell lymphoma, nasal type. This is an aggressive type of lymphoma that is very rare in the United States and Europe overall but more common in Asian and Hispanic communities. It can occur in children or adults, most often involving the nasal area and sinuses. It can also involve the trachea (windpipe), gastrointestinal tract, skin, or a man’s testicles. Standard chemotherapy does not always work well for this type of NHL, and combining radiation therapy with chemotherapy appears to be an important addition to treatment. Recently, a drug used for acute lymphoblastic leukemia called asparaginase (Elspar) has helped treat this subtype of lymphoma for patients who have been newly diagnosed or had the disease come back after treatment. Stem cell transplantation for this type of lymphoma is being studied in clinical trials.

Enteropathy-associated T-cell lymphoma. This type of lymphoma is rare in the United States but is more common in Europe. It is an aggressive form of T-cell lymphoma that involves the intestines of patients who have celiac disease (gluten intolerance). High-dose chemotherapy may be used to treat enteropathy type T-cell lymphoma.

Gamma/delta hepatosplenic T-cell lymphoma. This is an aggressive form of peripheral T-cell lymphoma that involves the liver and spleen. It occurs most often in adolescent and young men. It is treated as a high-risk diffuse large cell lymphoma (see above).

Subcutaneous panniculitis-like T-cell lymphoma. This is a form of peripheral T-cell lymphoma that is similar to gamma/delta hepatosplenic T-cell lymphoma (see above). It involves the tissue under the skin and is often first diagnosed as panniculitis (inflammation of fatty tissues). It is treated as a high-risk aggressive lymphoma.

Mycosis fungoides. This is a rare T-cell lymphoma that primarily involves the skin. It often has a very long and indolent course, but may become more aggressive and spread to lymph nodes or internal organs. Radiation therapy, chemotherapy, or immunotherapy can help treat this form of NHL. New drugs have been developed for the treatment of cutaneous lymphomas, some of which can be taken orally as a pill.

More information on the specific treatment options described above can be found in the Treatment Options section.

The next section helps explain the different stages for this type of cancer. Use the menu on the side of your screen to select Stages, or you can select another section, to continue reading this guide. 

Lymphoma - Non-Hodgkin - Stages

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will learn about how doctors describe lymphoma’s location and spread. This is called the stage. To see other pages, use the menu on the side of your screen.

Staging helps to describe where NHL is located, if or where it has spread, and whether it is affecting other parts of the body. Doctors use diagnostic tests to determine the cancer’s stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis. There are different stage descriptions for different types of cancer.

When staging NHL, doctors evaluate the following:

  • The number of cancerous lymph node areas
  • The location of the cancerous lymph nodes: regional (in the same area the cancer started) or distant (in other parts of the body)
  • Whether the cancerous lymph nodes are on one or both sides of the diaphragm (the thin muscle under the lungs and heart that separates the chest from the abdomen)
  • Whether the disease has spread to the bone marrow, spleen, or extralymphatic organs (organs that are not part of the lymphatic system), such as the liver, lungs, or brain

The stage of lymphoma describes the extent of spread of the tumor using the Roman numerals one through four (I, II, III, or IV). This staging system is helpful for the most common subtypes of lymphoma, but for other subtypes, the disease has often spread throughout the body when it is diagnosed. In these situations, the prognostic factors become more important (see International Prognostic Index and Functional status, below). It is important to remember that even stage IV lymphomas are often highly treatable. As explained in the Symptoms and Signs section, each stage may also be subdivided into “A” and “B” categories, based on the presence or absence of specific symptoms. 

Stage I: Either one of these conditions:

  • The cancer is found in one lymph node region (stage I).
  • The cancer has invaded one extralymphatic organ or site (identified using the letter “E”) but not any lymph node regions (stage IE).

Stage II: Either one of these conditions:

  • The cancer is in two or more lymph node regions on the same side of the diaphragm (stage II).
  • The cancer involves a single organ and its regional lymph nodes, with or without cancer in other lymph node regions on the same side of the diaphragm (stage IIE).

Stage III: There is cancer in lymph node areas on both sides of the diaphragm (stage III). There may also be involvement of an extralymphatic organ (stage IIIE); the spleen, using the letter “S” (stage IIIS); or both (stage IIIES).

Stage IV: Lymphoma is called stage IV if it has spread throughout organs beyond the lymph nodes. Lymphoma commonly spreads to the liver, bone marrow, or lungs. Stage IV lymphomas are common, and this stage is still very treatable.

Progressive: If the cancer becomes larger or spreads while the patient is being treated for the original lymphoma, it is called progressive disease. This is also called refractory NHL.

Recurrent: Recurrent lymphoma is lymphoma that has come back after treatment. It may return in the area where it first started or in another part of the body. Recurrence may occur shortly after the first treatment or years later. If there is a recurrence, the cancer may need to be staged again (called re-staging) using the system above.

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer-Verlag New York, www.cancerstaging.net.

International Prognostic Index

In addition to stage, a scale called the International Prognostic Index (IPI) is important in planning treatment for aggressive lymphomas. The IPI was developed based on evidence from thousands of patients with lymphoma. The results showed that certain features could help predict how well treatment would work, with patients classified into low-risk or high-risk groups depending on the risk factors listed below.

Features that the IPI identifies as risk factors:

  • Age 60 or older
  • Stage III or stage IV disease
  • Blood test results showing higher than normal levels of LDH (a group of substances found in the blood called lactate dehydrogenase)
  • Lower overall health or performance status
  • Cancer in more than one organ or site outside the lymph node region

For patients with follicular lymphoma, additional factors, such as the level of a patient’s hemoglobin (part of the blood) and the number of lymph node groups involved, are also considered.

These factors are used to estimate the chance of cure. For noncurable lymphoma, they help to predict how aggressive the lymphoma might be. This index is now used widely to help doctors make decisions about treatment recommendations.

Functional status

To determine a patient’s prognosis, the doctor may also test how well a patient is able to function and carry out daily activities by using a functional assessment scale, such as the Eastern Cooperative Oncology Group (ECOG) Performance Status or the Karnofsky Performance Scales (KPS).

ECOG Performance Status. A lower score indicates a better functional status. Typically, the better someone is able to walk and care for himself or herself, the better the prognosis.

0: Fully active, able to carry on all pre-disease performance without restriction

1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light house work or office work

2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours

3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours

4: Completely disabled; cannot carry on any self-care; totally confined to bed or chair

5: Dead

KPS. A higher score indicates a better functional status.

100: Normal, no complaints, no evidence of disease

90: Able to carry on normal activity; minor symptoms of disease

80: Normal activity with effort; some symptoms of disease

70: Cares for self; unable to carry on normal activity or active work

60: Requires occasional assistance but is able to care for needs

50: Requires considerable assistance and frequent medical care

40: Disabled; requires special care and assistance

30: Severely disabled; hospitalization is indicated, but death is not imminent

20: Very sick; hospitalization necessary; active treatment necessary

10: Approaching death; fatal processes progressing rapidly

0: Dead

Information about the cancer’s type, subtype, and stage, as well as prognostic factors, will help the doctor recommend a treatment plan. The next section helps explain the treatment options for this type of cancer. Use the menu on the side of your screen to select Treatment Options, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Treatment Options

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will learn about the different ways doctors use to treat people with this type of lymphoma. To see other pages, use the menu on the side of your screen.

This section outlines treatments that are the standard of care (the best proven treatments available) for this specific type of cancer. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study to test a new treatment to evaluate whether it is safe, effective, and possibly better than the standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials and Latest Research sections.

Treatment overview

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team.

There are three main treatments for NHL: chemotherapy, radiation therapy, and immunotherapy. Occasionally, surgery or stem cell transplantation may be considered. Often, combinations of these treatments are used. Descriptions of these treatment options are listed below. Treatment options and recommendations depend on several factors, including the type and stage of NHL, possible side effects, and the patient’s preferences and overall health. Take time to learn about your treatment options and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with your doctor and what you can expect while receiving the treatment. Learn more about making treatment decisions.

Watchful waiting

Some patients with indolent lymphoma may not need immediate treatment if they are otherwise healthy and the lymphoma is not causing any symptoms or problems with other organs. During watchful waiting (also called watch-and-wait or active surveillance), patients are closely monitored using physical examinations, CT scans or other imaging tests, and laboratory tests on a regular basis. Treatment only begins if the person develops symptoms or tests indicate that the cancer is getting worse. For some patients with indolent lymphoma, the watch-and-wait approach does not affect the chances of survival as long as they have regular and careful follow-up care.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells in the lymph nodes, lymph organs, and bone marrow, usually by stopping the cancer cells’ ability to grow and divide. It is the main treatment for NHL. Chemotherapy may be given by mouth or injected into a vein. Systemic chemotherapy is delivered through the bloodstream to reach cancer cells throughout the body. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication. A medical oncologist is most often the primary cancer specialist for patients with lymphoma. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

The chemotherapy regimen used depends on the stage and type of the NHL. The most common chemotherapy combination for the initial treatment of NHL is called CHOP and contains four drugs: cyclophosphamide (Cytoxan, Neosar), doxorubicin (Adriamycin), vincristine (Vincasar, Oncovin), and prednisone (multiple brand names). Recent evidence has shown that, for most patients with B-cell lymphoma, adding rituximab (see the section on monoclonal antibodies below) to CHOP works better than using CHOP alone.

The side effects of chemotherapy depend on the individual, type of drug and dose used, and how long it is taken, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. These side effects can be managed during treatment and usually go away once treatment is finished. Chemotherapy may also cause long-term side effects, also called late effects.

Learn more about chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Radiation therapy

Radiation therapy is the use of high energy x-rays or other particles to kill cancer cells and shrink cancerous tumors. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. Radiation treatment for NHL is usually external-beam radiation therapy, which is radiation given from a machine outside the body. A radiation therapy regimen usually consists of a specific number of treatments given over a set period of time.

Radiation therapy is usually given following or in addition to chemotherapy, depending on the NHL subtype. It is most often given for patients who have lymphomas that are located in only one area of the body or who have a lymph node that is particularly large (usually more than 10 centimeters). It may also be given for the treatment of pain or in very low doses to patients with advanced disease who have localized symptoms.

General side effects from radiation therapy may include fatigue and mild skin reactions. There may also be side effects related to the part of the body that received the radiation. For example, patients who have had radiation therapy directed at the chest may experience lung swelling and irritation, and patients who had radiation therapy to the bones may have low blood counts. Most side effects go away soon after treatment is finished, but radiation therapy may also cause late effects.

Learn more about radiation therapy.

Immunotherapy

Immunotherapy (also called biologic therapy) is designed to boost the body’s natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. Monoclonal antibodies, interferon, and vaccines are biologic therapies being tested in clinical trials as treatments for different subtypes of NHL. Each is described below.

Monoclonal antibodies. Monoclonal antibodies are directed against a specific protein and do not affect cells that don’t have the protein. A monoclonal antibody called rituximab is used to treat many different types of B-cell lymphoma. Rituximab works by targeting a molecule called CD20 that is located on the surface of all B cells and B-cell lymphomas. When the antibody attaches to this molecule, some lymphoma cells die, and others appear to become more likely to die with chemotherapy. Although it works well by itself, research shows that it worked better when added to chemotherapy for patients with most types of B-cell NHL. Rituximab is also given after remission for indolent lymphomas to increase the length of the remission.

Another monoclonal antibody, brentuximab vedotin, was approved in 2011 for the treatment of systemic anaplastic large cell lymphoma for patients who did not benefit from at least one type of chemotherapy and for Hodgkin lymphoma patients who did not benefit from stem cell transplantation or were unable to undergo stem cell transplantation. Research on the benefits of other newer monoclonal antibodies for lymphoma is ongoing.

Radiolabeled antibodies. Radiolabeled antibodies are monoclonal antibodies with radioactive particles attached that are designed to focus the radiation directly to the lymphoma cells. These types of drugs are new, and research is ongoing. In general, the radioactive antibodies are thought to be stronger than regular monoclonal antibodies but more damaging to the bone marrow. This type of therapy is also called radioimmunotherapy (RIT).

Learn more about immunotherapy.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which bone marrow that contains cancer is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than a bone marrow transplant, because it is stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

Stem cell transplantation is often an aggressive treatment and is generally used only for patients with NHL whose disease is progressive or recurrent (see the Stages section). However, in some NHL subtypes, such as mantle cell lymphoma and some T-cell lymphomas, stem cell transplantation may be recommended to prevent recurrence. Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of NHL, results of any previous treatment, and patient’s age and general health. It is very important to talk with a doctor at an experienced transplant center about the risks and benefits of stem cell transplantation.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cell: allogeneic (ALLO) and autologous (AUTO). The cells used in AUTO transplants come from the patients themselves, while those used in ALLO transplants come from “matched,” healthy donors.

In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and allow replacement blood stem cells to create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. These high doses are used since patients who undergo this treatment have disease that has proven to be resistant to normal chemotherapy doses. Higher doses of chemotherapy are more effective against recurrent NHL than standard doses of chemotherapy. Learn more about bone marrow and stem cell transplantation.

Getting care for symptoms and side effects

Lymphoma and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the disease, an important part of care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care can help a person at any stage of illness. People often receive treatment for the lymphoma and treatment to ease side effects at the same time. In fact, patients who receive both often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the cancer, such as chemotherapy, surgery, and radiation therapy. Talk with your doctor about the goals of each treatment in your treatment plan.

Before treatment begins, talk with your health care team about the possible side effects of your specific treatment plan and supportive care options. And during and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it is addressed as quickly as possible. Learn more about palliative care.

Recurrent NHL

A remission is when lymphoma cannot be detected in the body and there are no symptoms. This may also be called “no evidence of disease” or NED. 

A remission can be temporary or permanent. This uncertainty leads to many survivors feeling worried or anxious that the disease will come back. While many remissions are permanent, it’s important to talk with your doctor about the possibility of the disease returning. Understanding the risk of recurrence and the treatment options may help you feel more prepared if the lymphoma does return. Learn more about coping with the fear of recurrence.  

As explained in the Stages section, if the cancer does return after a remission, it is called recurrent cancer. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence).

When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence, including whether the cancer’s stage has changed. After testing is done, you and your doctor will talk about your treatment options. Treatment for recurrent NHL depends on three factors: where the cancer is, the type of treatment given previously, and the patient’s overall health. Often the treatment plan will include the therapies described above (such as chemotherapy, radiation therapy, immunotherapy, or stem cell transplantation), but they may be used in a different combination or given at a different pace. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent cancer.

People with recurrent cancer often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.

Progressive NHL

Some patients with NHL may not experience a complete remission and will have small amounts of residual disease that is stable or will have residual disease that is actively growing despite treatment. If there is a small amount of residual disease that is stable, some patients with indolent NHL may be observed for a period of time or be treated with monoclonal antibodies or other drugs. These patients may have breaks in treatment, sometimes lasting many years. If the lymphoma begins to grow or spread, this is called progression of disease, and active treatment would begin again. It is important to understand that remission is not always possible in some indolent lymphomas; however, patients can be safely monitored even if there is leftover disease, as long as there are no symptoms and the lymphoma has not affected blood counts or other organs.

For NHL patients with residual disease that is growing despite active treatment, see Refractory NHL below.

Refractory NHL

Sometimes, standard treatments stop working well for NHL (called progressive NHL), or the lymphoma may come back very quickly (within six months of standard treatment). This is called refractory NHL. Patients with this diagnosis are encouraged to talk with doctors who are lymphoma experts to discuss options for the best treatment plan. Learn more about seeking a second opinion before starting treatment, so you are comfortable with the treatment plan chosen. This discussion may include clinical trials.

Choice of treatment for refractory NHL depends on three factors: where the cancer is, the type of treatment given previously, and the patient’s overall health. The doctor may suggest chemotherapy, stem cell transplantation, or a clinical trial. Supportive care will also be important to help relieve symptoms and side effects.

For most patients, a diagnosis of refractory NHL is very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.

If treatment fails

Recovery from NHL is not always possible. If treatment is not successful or diagnosed at a very late stage, the disease may be called advanced lymphoma.

This diagnosis is stressful, and this is difficult to discuss for many people. However, people with advanced NHL, especially those with indolent lymphomas, may continue to live for a long time after a diagnosis of advanced cancer. It is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Making sure a person is physically comfortable and free from pain is extremely important.

Patients who have advanced cancer and who are expected to live less than six months may want to consider a type of palliative care called hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to think about where you would be most comfortable: at home, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative for many families. Learn more about advanced care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and bereavement.

The next section helps explain clinical trials, which are research studies. Use the menu on the side of your screen to select About Clinical Trials, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - About Clinical Trials

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will learn more about clinical trials, which are the main way that new medical approaches are tested to see how well they work. To see other pages, use the menu on the side of your screen.

Doctors and scientists are always looking for better ways to treat patients with NHL. To make scientific advances, doctors create research studies involving volunteers, called clinical trials.

Many clinical trials are focused on new treatments, evaluating whether a new treatment is safe, effective, and possibly better than the current (standard) treatment. These types of studies evaluate new drugs, different combinations of existing treatments, new approaches to radiation therapy or surgery, and new methods of treatment. Patients who participate in clinical trials are often among the first to receive new treatments before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

There are also clinical trials that study new ways to ease symptoms and side effects during treatment and manage the late effects that may occur after treatment. Talk with your doctor about clinical trials regarding side effects. In addition, there are ongoing studies about ways to prevent the disease.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that these studies are the only way to make progress in treating NHL. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with NHL.

Sometimes people have concerns that, by participating in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill.” The use of placebos in cancer clinical trials is rare. When a placebo is used in a study, it is done with the full knowledge of the participants. Find out more about placebos in cancer clinical trials.

To join a clinical trial, patients must participate in a process known as informed consent. During informed consent, the doctor should list all of the patient's options so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.

For specific topics being studied for NHL, learn more in the Latest Research section.

Patients who participate in a clinical trial may stop participating at any time for any personal or medical reason. This may include that the new treatment is not working or there are serious side effects. Clinical trials are also closely monitored by experts who watch for any problems with each study. It is important that patients participating in a clinical trial talk with their doctor and researchers about who will be providing their treatment and care during the clinical trial, after the clinical trial ends, and/or if the patient chooses to leave the clinical trial before it ends. 

Cancer.Net offers a lot of information about cancer clinical trials in other areas of the website, including a complete section on clinical trials and places to search for clinical trials for a specific type of cancer.

The next section helps explain the areas of research going on today about this type of cancer. Use the menu on the side of your screen to select Latest Research, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Latest Research

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will read about the scientific research being done now to learn more about this type of lymphoma and how to treat it. To see other pages, use the menu on the side of your screen.

Doctors are working to learn more about NHL, ways to prevent it, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Always talk with your doctor about the diagnostic and treatment options best for you.

Gene profiling. As scientists learn more about the genetics and the specific role that gene mutations (changes) have in the development of cancer, they are better able to classify and diagnose subtypes of NHL. These gene profiling methods can help estimate prognosis for patients with certain types of lymphoma and are used primarily in lymphoma research, but in the next few years it is likely that treatments will be designed that work against specific genetic changes and counteract their effects.

Immunotherapy. As explained in the Treatment Options section, many new antibodies are being developed that boost the body’s natural defenses against cancer. Some attach to the surface of tumor cells, while others have radioactive substances or chemotherapy attached to them and can deliver treatment directly to lymphoma cells.

Targeted therapies. Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to the cancer's growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to normal cells. There are many targeted treatments for lymphoma in early clinical trials and being studied in laboratories including BCL-2 inhibitors and aurora kinase inhibitors.

Vaccines. Several therapeutic vaccines have been studied in clinical trials, mostly for indolent lymphoma (see the Subtypes section for a description of this type of NHL). They are not meant to prevent lymphoma but to lower the chance that a lymphoma will come back after treatment with chemotherapy or antibody therapy. So far, results from vaccine studies have not shown better results than other treatments, but research to improve vaccines is ongoing.   

Other drug studies. Different combinations of chemotherapy and different chemotherapy schedules (sometimes with antibodies or radiolabeled antibodies) are being studied in clinical trials. Also, many new drugs that work differently from standard chemotherapy are now being evaluated in clinical trials.

Stem cell transplantation. The use of different types of stem cell transplantation, including allogeneic or reduced intensity (mini-allogeneic or non-ablative) transplants, are also being tested for patients with newly diagnosed disease and for those who have had a recurrence after the initial treatment. For many types of lymphoma, the best way to use stem cell transplantation is still uncertain, which is why clinical trials on this treatment are in progress. Learn more about stem cell transplantation.

Supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current NHL treatments in order to improve patients’ comfort and quality of life.

Looking for More about the Latest Research?

If you would like additional information about the latest areas of research regarding NHL, explore these related items that take you outside of this guide:

The next section addresses how to cope with the symptoms of the disease or the side effects of its treatment. Use the menu on the side of your screen to select Coping with Side Effects, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Coping with Side Effects

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find out more about steps to take to help cope with physical, social, and emotional side effects. This page includes several links outside of this guide to other sections of this website. To see other pages, use the menu on the side of your screen.

Fear of treatment side effects is common after a diagnosis of lymphoma, but it may help to know that preventing and controlling side effects is a major focus of your health care team. This is called palliative or supportive care, and it is an important part of the overall treatment plan, regardless of the stage of disease.

Common side effects from each treatment option for NHL are described in detail within the Treatment Options section. Learn more about the most common side effects of lymphoma and different treatments, along with ways to prevent or control them. Side effects depend on a variety of factors, including the stage, the length and dosage of treatment(s), and your overall health.

Before treatment begins, talk with your doctor about possible side effects of each type of treatment you will be receiving. Ask which side effects are most likely to happen, when they are likely to occur, and what can be done to prevent or relieve them. And, ask about the level of caregiving you may need during treatment and recovery, as family members and friends often play an important role in the care of a person with NHL. Learn more about caregiving.

In addition to physical side effects, there may be psychosocial (emotional and social) effects as well. Patients and their families are encouraged to share their feelings with a member of their health care team who can help with coping strategies. Learn more about the importance of addressing such needs, including concerns about managing the cost of your cancer care

During and after treatment, be sure to tell the health care team about the side effects you experience, even if you feel they are not serious. Sometimes, side effects can last beyond the treatment period, called a long-term side effect. A side effect that occurs months or years after treatment is called a late effect. Treatment of both types of effects is an important part of survivorship care. Learn more by reading the Late Effects of Treatment and After Treatment sections or talking with your doctor.

The next section helps explain some late effects of cancer and cancer treatment. Use the menu on the side of your screen to select After Treatment, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Late Effects of Treatment

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find out more about side effects that can occur long after treatment for this type of lymphoma has ended. To see other pages, use the menu on the side of your screen.

Patients who have been treated for lymphoma have an increased risk of developing other diseases or conditions later in life, as chemotherapy and radiation therapy can cause permanent damage to healthy parts of the body. Treatments have improved in the last 30 years, and now patients who have received treatment for lymphoma are less likely to experience late effects; however, there is still some risk. Therefore, it is important that people receive follow-up care to watch for the late effects explained below.

  • People who have received radiation therapy to the pelvis, high doses of cyclophosphamide, and high-dose chemotherapy for stem cell transplantation are at risk for infertility (inability to have children). Learn more about fertility and cancer treatment.
  • All survivors of lymphoma have a higher risk than the general population of developing a secondary cancer. This increased risk continues for up to 20 years after treatment. The most common secondary cancers include cancer of the lung, brain, kidney, or bladder; melanoma; Hodgkin lymphoma; or leukemia.
  • Women who have received radiation therapy to the chest before age 35 have an increased risk of breast cancer.
  • Patients who have received doxorubicin-based chemotherapy or radiation treatment to the chest may be at higher risk for developing heart problems.
  • Adults who have received chemotherapy, such as alkylating agents and methotrexate (multiple brand names), or radiation therapy to the chest area may be at risk for lung damage and shortness of breath later in life.
  • Patients who have received radiation therapy to the neck have an increased risk of low levels of thyroid hormones later in life.
  • Patients who have received stem cell transplantation may be at higher risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
  • Children who have received radiation therapy and chemotherapy to the brain and spinal cord area may be at risk for growth problems, learning disabilities, and delayed puberty. Teenagers who receive chemotherapy may be at higher risk for low sperm counts (for boys) or damage to the ovaries (for girls).
  • Children who have received total body irradiation (TBI) as part of the stem cell transplantation process may experience thyroid problems.

Learn more about late effects of cancer treatment.

The next section helps explain medical tests and check-ups needed after finishing cancer treatment to help identify and manage these late effects. Use the menu on the side of your screen to select After Treatment, or you can select another section, to continue reading this guide.

Lymphoma - Non-Hodgkin - After Treatment

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will read about your medical care after treatment for NHL has finished and why this follow-up care is important. To see other pages, use the menu on the side of your screen.

After completing your treatment for NHL, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years. For the first two years, visits to the doctor are usually scheduled every two or three months. If there is no evidence of disease, patients will not have to see the doctor as often but should still return at least once a year for a checkup. Normally, follow-up visits are most frequent in the first three years after treatment. Follow-up visits should continue throughout the person’s lifetime.

During this time, most doctors will monitor the disease with CT scans or PET scans. Although these are very important tools for determining the disease’s response to treatment and monitoring for recurrence, there is some debate over how often CT scans and PET scans should be used. As described in the Diagnosis section, both of these imaging tests cause the person to be exposed to a small amount of radiation, and an integrated (combined) PET-CT scan causes more radiation exposure than either one alone. In the past, these types of imaging tests were done every four to six months for up to five years after the last chemotherapy treatment. Now most physicians agree that performing routine scans, particularly when the person has no symptoms, may be exposing patients to unnecessary radiation, but there is limited guidance on how often these scans should be performed. Talk with your doctor about the risks and benefits of these tests and whether another type of test that involves less exposure to radiation can be done.

ASCO offers cancer treatment summary forms to help keep track of the cancer treatment you received and develop a survivorship care plan once treatment is completed.

People recovering from NHL are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, not smoking, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about the next steps to take in survivorship, including making positive lifestyle changes.

The next section offers a list of questions you may want to ask. Use the menu on the side of your screen to select Questions to Ask the Doctor, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Questions to Ask the Doctor

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find some questions to ask your doctor or other members of your health care team, to help you better understand your diagnosis, treatment plan, and overall care. To see other pages, use the menu on the side of your screen.

Talking often with the doctor is important to make informed decisions about your health care. These suggested questions are a starting point to help you learn more about your cancer care and treatment. You are also encouraged to ask additional questions that are important to you. You may want to print this list and bring it to your next appointment, or download Cancer.Net’s free mobile app for an e-list and other interactive tools to manage your care.

  • Which type and subtype of lymphoma do I have?
  • Did a pathologist experienced in the diagnosis of lymphoma review the biopsy?
  • Can you explain my pathology report (laboratory test results) to me?
  • Should I get a second opinion? Will this include a specialized pathologist reviewing the biopsy?
  • How many patients do you see with this type of lymphoma each year?
  • Are you Board certified? Do you have sub-specialty boards in hematology, oncology, or radiation oncology?
  • Where in my body has the disease spread?
  • What stage is the lymphoma? What does this mean?
  • What are my treatment options?
  • Will I need surgery?
  • Will I need chemotherapy?
  • Will I need radiation therapy?
  • What is immunotherapy? Is this treatment appropriate for me?
  • What clinical trials are open to me?
  • Why is it sometimes appropriate to “watch and wait?” Is this an option for me?
  • What treatment plan do you recommend?
  • What is the goal of each treatment? Is it to eliminate the cancer, help me feel better, or both?
  • Is my lymphoma curable? If so, what are the chances for a cure? If not, can the disease be controlled?
  • Who will be part of my health care team, and what does each member do?
  • Who will be coordinating my overall treatment and follow-up care?
  • What are the possible side effects of this treatment, both in the short term and the long term?
  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
  • Could this treatment affect my sex life? If so, how and for how long?
  • Could this treatment affect my ability to become pregnant or have children? If so, should I talk with a fertility specialist before cancer treatment begins?
  • If I’m worried about managing the costs related to my cancer care, who can help me with these concerns?
  • What caused my lymphoma?
  • How can I stay as healthy as possible during and after treatment?
  • What follow-up tests will I need, and how often will I need them?
  • What support services are available to me? To my family?
  • Whom should I call for questions or problems?

The next section offers some more resources that may be helpful to you. Use the menu on the side of your screen to select Additional Resources, or you can select another section, to continue reading this guide.  

Lymphoma - Non-Hodgkin - Additional Resources

This section has been reviewed and approved by the Cancer.Net Editorial Board, 09/2013

ON THIS PAGE: You will find some helpful links to other areas of Cancer.Net that provide information about cancer care and treatment. This is the final page of Cancer.Net’s Guide to Non-Hodgkin Lymphoma. To go back and review other pages, use the menu on the side of your screen.

Cancer.Net includes many other sections about the medical and emotional aspects of cancer, both for the person diagnosed and their family members and friends. This website is meant to be a resource for you and your loved ones from the time of diagnosis, through treatment, and beyond. Here are a few sections that may get you started in exploring the rest of Cancer.Net:

This is the end of Cancer.Net’s Guide to Non-Hodgkin Lymphoma. Use the menu on the side of your screen to select another section, to continue reading this guide.