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Lymphoma - Non-Hodgkin - Introduction

Approved by the Cancer.Net Editorial Board, 08/2019

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. Use the menu to see other pages. Think of that menu as a roadmap for this complete 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, chest, underarms, and neck.

The lymphatic system carries lymph, a colorless fluid that contains a type of white blood cell called lymphocytes. Lymphocytes are part of the immune system and help fight germs in the body. Types of lymphocytes include:

  • B-lymphocytes, also called B cells, which make antibodies that fight bacteria and other infections

  • T-lymphocytes, also called T cells, which destroy viruses and foreign cells and trigger the B cells to make antibodies

  • Natural killer cells (NK cells), which destroy certain invaders, such as viruses, cells infected by viruses, and some cancer cells

Other parts of the lymphatic system include the:

  • Spleen, which makes lymphocytes and filters the blood

  • Thymus, an organ under the breastbone

  • Tonsils, located in the throat

  • Bone marrow, the spongy red tissue inside bones that makes:

    • White blood cells, which fight infection

    • Red blood cells, which carry oxygen throughout the body

    • Platelets, which help the blood clot

About non-Hodgkin lymphoma

Lymphoma is a cancer of the lymphatic system. Lymphoma begins when healthy B cells, T cells, or NK cells in the lymphatic system change and grow out of control, which 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 a group of cancers of the lymphatic system. These cancers can have different symptoms and signs, findings on a physical examination, and treatments.

Because lymphatic tissue is found in most parts of the body, NHL can start almost anywhere and can spread, or metastasize, to almost any organ. It often begins in the lymph nodes, liver, spleen, or bone marrow. However, 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 of lymphoma has been diagnosed. That information can help the doctor figure out the best treatment, as well as a patient’s prognosis, which is the chance of recovery. More information can be found in the Subtypes section of this guide.

This guide covers NHL in adults. A different guide on this website covers childhood NHL.

Looking for More of an Introduction?

If you would like more of an introduction, explore these related items. Please note that these links will take you to other sections on Cancer.Net:

The next section in this guide is Statistics. It helps explain the number of people who are diagnosed with NHL and general survival rates. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Statistics

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will find information about the number of people who are diagnosed with NHL each year. You will also read general information on surviving the disease. Remember, survival rates depend on several factors. Use the menu to see other pages.

This year, an estimated 74,200 people (41,090 men and 33,110 women) in the United States will be diagnosed with NHL. While some subtypes of NHL are common in children, NHL is far more common in adults and risk increases with age. Over half of patients are age 65 or older when diagnosed. NHL is the seventh most common cancer in both men and women. The disease accounts for 4% of all cancers in the United States.

It is estimated that 19,970 deaths (11,510 men and 8,460 women) from this disease will occur this year. It is the ninth most common cause of cancer death among both men and women. The survival rate has been improving since the late 1990s, thanks to treatment advances. From 2007 to 2016, the death rate decreased by 2% annually.

The 5-year survival rate tells you what percent of people live at least 5 years after the cancer is found. Percent means how many out of 100. The overall 5-year survival rate for people with NHL is 71%. For men, the 5-year survival rate is 69%. For women, it’s 72%. For stage I NHL, the 5-year survival rate is almost 82%. For stage II the 5-year survival rate is 75% and for stage III it is 69%. For stage IV NHL, the 5-year survival rate is almost 62%. These survival rates vary depending on the cancer’s stage and subtype.

It is important to remember that statistics on the survival rates for people with NHL are an estimate. The estimate comes from annual data based on the number of people with this cancer in the United States. Also, experts measure the survival statistics every 5 years. So the estimate may not show the results of better diagnosis or treatment available for less than 5 years. Talk with your doctor if you have any questions about this information. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society’s (ACS) publications, Cancer Facts & Figures 2019 and Cancer Facts & Figures 2017, the ACS website (January 2019), and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database.

The next section in this guide is Medical Illustrations. It offers drawings of body parts often affected by NHL. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Medical Illustrations

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will find a drawing of the parts of the lymphatic system. Use the menu to see other pages.

This illustration of the lymphatic system shows the lymphatic vessels, which are thin tubes that branch out to all parts of the body. It also shows the spleen, located on the left side of the body under the liver, and the thymus, located behind the breastbone. Groups of lymph nodes, tiny bean-shaped organs, are located throughout the body at different areas in the lymphatic system. The largest groups of lymph nodes are shown in the abdomen, groin, pelvis, underarms, and neck. A cross section of a lymph node shows that veins, arteries, and lymphatic vessels allow blood and lymph to flow through a system of lymph nodules in the cortex of the lymph node. Copyright 2004 American Society of Clinical Oncology. Robert Morreale/Visual Explanations, LLC

The next section in this guide is Risk FactorsIt explains the factors that may increase the chance of developing NHL. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Risk Factors

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will find out more about the factors that increase the chance of developing NHL. Use the menu to see other pages.

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. 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, and most people diagnosed with NHL will not learn what caused it. However, the following factors may raise a person’s risk of developing NHL:

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

  • Gender. Men are very slightly more likely to develop NHL than women.

  • Bacterial infections. Some types of NHL are associated with specific infections. For example, mucosa-associated lymphoid tissue (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. Infections may also cause other types of MALT lymphoma, including those affecting the lungs, tear glands, and skin.

  • Viruses. Viruses cause some types of NHL. The Epstein-Barr virus (EBV) is the virus that causes mononucleosis, also known as "mono," and it is associated with some types of NHL. These include Burkitt lymphoma, lymphomas occurring after an organ transplant, and, rarely, other lymphomas in people who are otherwise healthy. Nearly everyone has EBV, so the virus is probably not the only factor that determines cancer risk. NHL that arises from EBV is likely the result of the body’s inability to regulate the virus. Therefore, people who have had mononucleosis 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 of the spleen (see Subtypes). Researchers have also found other viruses 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. Some drugs used to treat autoimmune disorders may increase the risk of NHL.

  • Organ transplantation. Organ transplant recipients have a higher risk of NHL. This is because of the drugs patients must take to reduce immune system function in order to protect the transplanted organ from rejection.

  • 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 may increase the risk of NHL. This may include pesticides, herbicides (like Agent Orange), and petrochemicals.

  • Genetic factors. Currently there are no widely accepted genetic tests to identify inherited risk factors for NHL or that reliably predict a person’s risk of developing NHL. These possible risks are being studied in ongoing clinical trials.

  • Vaccines. The relationship between vaccinations and lymphoma remains unclear and controversial. A number of studies have found an association between Bacillus Calmette–Guerin (BCG) vaccination and an increased risk of NHL. BCG is a vaccine for tuberculosis disease that is used to treat some cases of bladder cancer. Conversely, research has also associated other vaccinations with a decreased risk of NHL, such as those for smallpox, cholera, yellow fever, influenza, measles, tetanus, and polio.

  • Breast implants. Having breast implants can increase the risk of breast lymphomas.

  • Exposure to ionizing radiation. This can include exposure to radiation from atomic bombs, nuclear reactor accidents, and medical radiation therapy.

  • Diet/weight. There is some inconclusive evidence that being overweight or having a diet filled with fatty foods or red meat may slightly increase the risk of lymphoma.

The next section in this guide is Symptoms and Signs. It explains what body changes or medical problems NHL can cause. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Symptoms and Signs

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. Use the menu to see other pages.

People with NHL may experience a variety of symptoms. However, many people, especially those with follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, and indolent subtypes, will have no symptoms. Conditions that are not lymphoma can also cause many of these symptoms.

There are very few changes, or symptoms, that are specific to lymphoma. This explains why it is sometimes difficult to make a diagnosis. 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.

  • An enlarged spleen may cause back pain and a feeling that the stomach is full.

  • A tumor in the groin may cause swelling in the legs.

  • A tumor in the underarms may cause swelling in the arms.

  • If the lymphoma spreads to the brain, there may be symptoms similar to those of a stroke.

  • A tumor in the center of the chest may press on the trachea and cause coughing, chest pain, difficulty breathing, or other respiratory problems.

If you are concerned about any changes you experience, please talk with your doctor. Your doctor will ask you how long and often you’ve been experiencing the symptoms, in addition to other questions. This is to help figure out the cause of the problem, called a diagnosis.

If NHL is diagnosed, your doctor may also use certain symptoms to help describe the disease, called staging. For many decades, doctors divided each stage of NHL into “A” and “B” categories based on specific symptoms, as listed below. However, the most recent staging system published in 2014, known as the Lugano Classification, removed these categories because they do not necessarily change the way the lymphoma is treated.

  • A means that a person has not experienced B symptoms.

  • B means that a person experienced the following symptoms:

    • Unexplained weight loss of more than 10% of their original body weight during the 6 months before diagnosis.

    • Unexplained fever with temperatures above 100.4ºF (38ºC).

    • Drenching night sweats. Most patients say that either their nightclothes or the sheets on the bed are actually soaked. Sometimes, heavy sweating occurs during the day.

Once a doctor diagnoses and stages NHL, relieving symptoms remains an important part of cancer care and treatment. This may be called palliative care or supportive care. It is often started soon after diagnosis and continued throughout treatment. Be sure to talk with your health care team about the symptoms you experience, including any new symptoms or a change in symptoms.

The next section in this guide is Diagnosis. It explains what tests may be needed to learn more about the cause of the symptoms. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Diagnosis

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will find a list of common tests, procedures, and scans that doctors use to find the cause of a medical problem. Use the menu to see other pages.

Doctors use many tests to find, or diagnose, cancer. They also do tests to learn what parts of the body are affected by the cancer. Because the lymph system is throughout the body, any lymph organ may be involved with NHL. Imaging tests can show pictures of the inside of the body and help doctors find which areas of the body may be involved with the cancer. Doctors may also do tests to learn which treatments could work best.

For most types of cancer, a biopsy is the only sure way for the doctor to know if an area of the body has cancer. In a biopsy, the doctor takes a small sample of tissue for testing in a laboratory. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis.

This section describes options for diagnosing NHL. Not all tests listed below will be used for every person. Your doctor may consider these factors when choosing a diagnostic test:

  • The type of lymphoma suspected

  • Your signs and symptoms

  • Your age and general health

  • The results of earlier medical tests

To determine if a person has NHL, the doctor will first take a complete medical history. He or she will also 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, they will recommend a biopsy, as well as laboratory and imaging tests.

In addition to a physical examination, 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. Other tests can suggest that cancer is present, but only a biopsy can make a definitive diagnosis and find out the subtype. This tissue may be removed using a core biopsy needle or surgery. To diagnose lymphoma, tissue is usually taken from 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 scan (CT scan, see below) or an ultrasound (see below) or from the stomach or intestine during an endoscopy. An endoscopy is 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 which subtype of lymphoma is suspected.

    Having enough tissue in the biopsy sample is very important in making a diagnosis. Needle biopsy samples are rarely big enough to make a definite diagnosis of lymphoma. In most cases, a core biopsy or surgical biopsy is needed to correctly diagnose and classify the lymphoma. A pathologist or a hematopathologist experienced in diagnosing lymphoma then analyzes the samples. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. A hematopathologist is a pathologist who has additional training in the diagnosis of blood cancer. Because there are so many subtypes of lymphoma and because some of these subtypes are uncommon or rare, getting a second opinion that includes a formal hematopathology review of previous tissue biopsies may be helpful.

  • Computed tomography (CT or CAT) scan. A CT scan takes pictures of the inside of the body using x-rays taken from different angles. A computer combines these pictures into a detailed, 3-dimensional image that shows any abnormalities or tumors. A CT scan can be used to measure the tumor’s size. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein, given as a pill or liquid to swallow, or both. A doctor who specializes in performing imaging tests to diagnose disease, called a radiologist, interprets CT scans. CT scans of the chest, abdomen, and pelvis can help find cancer that has spread to the lungs, lymph nodes, spleen, and liver.

  • Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. MRI can be used to measure the tumor’s size. A special dye called contrast medium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein. A radiologist interprets the scan.

  • Positron emission tomography (PET) or PET-CT scan. A PET scan is usually combined with a CT scan (see above), called a PET-CT scan. However, you may hear your doctor refer to this procedure just as a PET scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive sugar substance is injected into the patient’s body. This sugar substance is taken up by cells that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body. A nuclear medicine physician interprets the scan. A doctor can use this technique to look at both the structure of the tumor and how much energy the tumor and healthy tissues use. If, after 1 or more imaging tests, the doctor decides the lymphoma might be affecting the bone marrow, they may recommend a bone marrow biopsy.

  • Bone marrow aspiration and biopsy. These 2 procedures are similar and typically done at the same time to examine the bone marrow. Bone marrow has both a solid and a liquid part. A bone marrow aspiration removes a sample of the fluid with a needle. A bone marrow biopsy is the removal of a small core of solid tissue using a needle.

    A pathologist or hematopathologist then analyzes the sample(s). A common site for a bone marrow aspiration and biopsy is the pelvic bone, which is located in the lower back by the hip. Doctors generally give a type of medication called "local anesthesia" beforehand to numb the area. Anesthesia is medication that blocks the awareness of pain. Stronger types of anesthesia can also be used to lessen the pain.

    Lymphoma often spreads to the bone marrow, so looking at a sample of the bone marrow can be important for diagnosing lymphoma and determining the stage. The doctor can also use the sample removed during the aspiration to find any genetic changes. With certain types of lymphoma, these procedures may not be required if a PET scan has been done.

  • Testing of the tumor. Your doctor may recommend running laboratory tests on a tumor and/or bone marrow sample to identify specific genes, proteins, and other factors unique to the disease. Results of these tests can help determine your treatment options. There are several types of molecular and genetic testing:

    • Cytogenetics studies healthy and abnormal chromosomes in dividing cancer cells.

    • Fluorescent in situ hybridization (FISH) uses fluorescent probes under a special microscope to detect changes in specific chromosomes.

    • Flow cytometry looks at proteins that are on the surface or inside a cancer cell.

    • Immunohistochemistry (IHC) is a special staining process to look at proteins on the surface of or inside the cancer cell.

    • Polymerase chain reaction (PCR) detects specific DNA sequences that occur in some cancers.

    • Extended molecular profiling is used to evaluate changes in specific genes in the tumor cells.

After diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is NHL, these results also help the doctor describe the subtype and stage of the NHL.

The next section helps explain the different subtypes of NHL that may be diagnosed. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Subtypes

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will find descriptions of the most common types and subtypes of NHL. You will also find information about how each subtype may be treated. Use the menu to see other pages.

There are different types and subtypes of NHL. It is very important to know which type and subtype have been diagnosed. Below are the most common types and subtypes, including information about how each may be treated. For more information about the treatment options described here, see the Types of Treatment section.

Types of NHL

First, the doctor will determine what type of cell the lymphoma started in and classify the disease within 1 of the 3 major groups:

  • B-cell lymphoma. About 90% of people in western countries with lymphoma have B-cell lymphoma.

  • T-cell lymphoma. About 10% of people with lymphoma have T-cell lymphoma. These lymphomas are more frequent in Asian countries.

  • 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, either “indolent” or “aggressive.” Indolent and aggressive NHL are equally common in adults. In children, aggressive NHL is more common. Some subtypes of lymphoma cannot easily be classified as indolent or aggressive. For example, mantle cell lymphoma (see below) has both indolent and aggressive NHL features.

Indolent NHL

These types of lymphoma grow 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 usually started when they develop symptoms or the disease begins to change. This is called watchful waiting or active surveillance. In cases where there are many cancer cells in the body, called high-burden disease, treatment will be started even if there are no symptoms.

When indolent lymphoma is located only in 1 or 2 adjacent areas, it is called localized disease (stages I and II, see the Stages section). For people with localized disease, radiation therapy is often used. However, most patients with indolent NHL have stage III or IV disease at the time of diagnosis. There are many effective treatments for these stages of indolent NHL. However, it may come back months or years after treatment has finished and require more treatment.

Aggressive NHL

These types of lymphoma may develop rapidly, and treatment is usually started within weeks. These types of lymphoma usually need more intensive chemotherapy. The doctor may recommend adding radiation therapy to treat stage I or II disease or to treat lymphoma where the site of the disease is large, sometimes called “bulky” disease. Some forms of aggressive lymphoma may be cured with effective treatment.

Subtypes of NHL

In addition to determining if the NHL is indolent or aggressive and whether it is B-cell, T-cell, or NK-cell lymphoma, it is very important to determine the subtype of NHL. This is because each subtype can behave differently and may require different treatments. There are more than 60 NHL subtypes, although some are quite rare. The most common subtypes are described below, along with some basic information about different treatments. Learn more in the Types of Treatment section.

Distinguishing among the different subtypes of NHL can be difficult and requires pathologists or hematopathologists who are experts in the diagnosis of lymphoma. These specialists use sophisticated techniques and work closely with experienced oncologists. The diagnosis is based on how the lymphoma looks under the microscope. The doctors confirm the diagnosis with 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

These are the common subtypes of B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common form of lymphoma. About 30% of NHL in the United States is DLBCL. It is an aggressive form of NHL that involves organs other than the lymph nodes about 40% of the time. About 2 out of 3 people with DLBCL are cured with chemotherapy given in combination with rituximab (Rituxan). Radiation therapy is also used for some people, especially if the lymphoma is found in a limited area. Your doctor may check the fluid around the brain, called cerebrospinal fluid (CSF), in certain cases at diagnosis and recommend treatments to prevent the lymphoma from spreading to the brain, called central nervous system (CNS) prophylaxis. However, most people do not need this type of treatment.

Recent research shows that there are different types of DLBCL, including germinal center and non-germinal center. Research studies, called clinical trials, continue to look at whether patients should receive different types of treatment for these different types of DLBCL.

Follicular lymphoma. Follicular lymphoma is the second most common form of lymphoma in the United States and Europe. About 20% of people with NHL have this subtype. It usually begins in the lymph nodes, is most often indolent, and grows very slowly. People with early, stage I follicular lymphoma may be cured with radiation therapy. For some, bone marrow/stem cell transplantation may cure the disease. Patients with follicular lymphoma may receive a combination of chemotherapy, targeted therapy, and/or radiation therapy. Or, they may be followed closely with watchful waiting and start treatment only when symptoms appear.

Recent clinical trials suggest that people with follicular lymphoma have lived longer over the last few decades. Research shows that some monoclonal antibodies alone or in combination with drugs such as bendamustine (Treanda) and lenalidomide (Revlimid) are effective for this subtype. There are many new drugs being tested for the treatment of follicular lymphoma. Over time, follicular lymphoma may turn into DLBCL (see above), which will then require more aggressive treatment. This is called transformation. If follicular lymphoma transforms, it can be treated the same way as DLBCL.

Localized radiation therapy is often a common treatment choice for people with stage I follicular lymphoma and for some people with stage II follicular lymphoma.

Mantle cell lymphoma. About 5% to 7% of people with NHL have mantle cell lymphoma. It most often appears in people older than 60 and is much more common in men than in women. It usually involves the bone marrow, lymph nodes, spleen, and gastrointestinal system, which includes the esophagus, stomach, and intestines. Mantle cell lymphoma is identified by a protein called cyclin D1 or by a genetic change within the lymphoma cells involving chromosomes 11 and 14. Some patients have a slower-growing form of the disease and if they do not have symptoms or a significant amount of disease, some may be monitored using the watchful waiting approach.

Treatment of mantle cell lymphoma often uses a combination of chemotherapy and a monoclonal antibody, which is a type of targeted therapy. For younger patients who are otherwise healthy, high-dose chemotherapy and autologous bone marrow transplantation often results in the longest remission, and they may receive maintenance therapy with the rituximab. For older patients or those who are not able to receive an autologous bone marrow transplant, maintenance therapy with rituximab is a standard treatment approach.

If chemotherapy does not work or the disease comes back, called recurrence, there are differing opinions on the best way to treat mantle cell lymphoma. Research shows that drugs such as acalabrutinib (Calquence), ibrutinib (Imbruvica), and lenalidomide may be effective. Researchers are studying these drugs as part of first-line treatment. Researchers are also studying new drugs for mantle cell lymphoma.

Small lymphocytic lymphoma. This type of lymphoma is the same disease as B-cell chronic lymphocytic leukemia (CLL) without a significant amount of disease in the blood. About 5% of people with NHL have this subtype, which is considered indolent lymphoma. People with small lymphocytic lymphoma may not require treatment, but instead receive watchful waiting. Some patients receive a combination of chemotherapy and a targeted therapy.

First-line treatment may include a combination of ibrutinib and obinutuzumab (Gazyva), which is a monoclonal antibody. Ibrutinib alone is also approved by the U.S. Food and Drug Administration (FDA) to treat small lymphocytic lymphoma that has come back after treatment. Another targeted therapy, venetoclax (Venclexta), in combination with obinutuzumab is approved as a first treatment for small lymphocytic lymphoma. Venetoclax may also be used in combination with rituximab.

Double hit/triple hit lymphoma. This is a highly aggressive subtype, accounting for about 5% of cases. Rarely, low-grade follicular lymphoma may also transform into double hit lymphoma. Double hit lymphomas have changes in the MYC gene and in either the BCL2 or BCL6 gene. Double hit lymphoma is often diagnosed in older adults. There is currently no established treatment regimen, although combinations of chemotherapy and rituximab are the most common options. Triple hit lymphomas have changes in the MYC, BCL2, and BCL6 genes.

Primary mediastinal large B-cell lymphoma. This is an aggressive form of DLBCL (see above). It appears as a large mass in the chest area. The mass may cause breathing problems or superior vena cava (SVC) syndrome, a collection of symptoms caused by the partial blockage or compression of the superior vena cava. The superior vena cava is 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. About 2.5% of people with NHL have this subtype. Most often, doctors treat it with combination chemotherapy plus rituximab. Radiation therapy to the chest may be used in people for whom chemotherapy did not work. For lymphoma that has not responded to chemotherapy and radiation, CAR T-cell therapy may be an option. A closely related lymphoma called mediastinal grey-zone lymphoma (MGZL) may also occur in the same age group. It is treated in a manner similar to that of primary mediastinal large B-cell lymphoma.

Splenic marginal zone B-cell lymphoma. This type of lymphoma begins in the spleen and usually involves the bone marrow and the blood. It is usually slow growing, and the treatment approach is often watchful waiting. If treatment is needed, rituximab is often used, although some patients may also need chemotherapy. In some circumstances, surgical removal of the spleen may be needed.

Extranodal marginal zone B-cell lymphoma of MALT. This type of lymphoma most commonly occurs in the stomach. However, it may also occur in the lung, skin, thyroid, salivary gland, or in the orbit, adjacent to the eye, or in the bowel. Patients with this type of lymphoma sometimes have a history of autoimmune disease, such as lupus, rheumatoid arthritis, or Sjögren syndrome. When MALT occurs in the stomach, it is sometimes caused by a bacteria called Helicobacter pylori. When MALT is caused by this bacteria, antibiotics can sometimes effectively treat the disease. For disease only affecting only 1 organ, radiation therapy can sometimes cure MALT. Rituximab with or without chemotherapy is also sometimes used to treat MALT.

Nodal marginal zone B-cell lymphoma. This rare type of indolent lymphoma involves the lymph nodes. About 1% of people with lymphoma have this subtype. In general, doctors treat this subtype of lymphoma 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 often involves the bone marrow, sometimes lymph nodes, and spleen. In many patients, this lymphoma produces a protein, called an “M protein,” that is found in the blood. When this occurs, the condition is called Waldenstrom’s macroglobulinemia (WM). Patients with WM sometimes have elevated serum viscosity, or “thickened” blood, which may cause symptoms such as headache, blurry vision, dizziness, and shortness of breath. Changes in the MYD88 gene are detected in more than 90% of cases of lymphoplasmacytic lymphoma and WM. Looking for mutations in this gene may be helpful in diagnosing lymphoplasmacytic lymphoma. Treatment may include:

  • Watchful waiting

  • Chemotherapy

  • Targeted therapy with monoclonal antibodies

  • Combinations of chemotherapy and monoclonal antibodies

Clinical trial researchers are studying using chemotherapy followed by bone marrow transplantation as a treatment option, which may be useful if the lymphoma returns after initial treatment.

Primary effusion lymphoma. This rare and very aggressive form of lymphoma most often occurs in people:

  • Who have the human immunodeficiency virus (HIV), which causes autoimmune deficiency syndrome (AIDS)

  • Whose immune system does not work well for other reasons

  • Who are elderly

This lymphoma often shows up as fluid around the lung, heart, or abdominal cavity. Often, there are no tumor masses. It is treated the same way 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 3 forms of Burkitt lymphoma:

  • Endemic

  • Sporadic

  • Immunodeficiency-related lymphoma

The endemic subtype 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 sometimes appears with a mass in the abdomen, but it can affect many other parts of the body. Because this type of lymphoma spreads quickly, it needs immediate treatment. This subtype often has abnormalities involving the MYC gene, which can contribute to cancer growth.

Burkitt lymphoma is often curable. A series of treatments with chemotherapy, each usually given over several days in a hospital, can lead to long-term remission in more than 80% of patients.

Subtypes of T-cell and NK-cell lymphoma

These are the most common subtypes of T-cell and NK-cell lymphoma:

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.

Anaplastic large cell lymphoma, systemic type. This form makes up about 2% of all lymphomas and about 10% of all childhood lymphomas. In people with this subtype, an increased amount of the ALK-1 protein may be found in the cancer cells. Those who have ALK-1 protein in the cancer cells often have a better prognosis than those who do not have the ALK-1 protein in the cancer cells. This is an aggressive form of lymphoma, but chemotherapy often works well. New treatments, such as the targeted therapy brentuximab vedotin (Adcetris) or bone marrow transplantation, may sometimes be a treatment option.

Breast implant-associated anaplastic large cell lymphoma. This is a relatively recently recognized subtype that arises in areas near breast implants. It is usually less aggressive than the systemic type of anaplastic large cell lymphoma, and treatment includes surgical removal of the implant.

Peripheral T-cell lymphoma, not otherwise specified (NOS). This is an aggressive form of lymphoma that is often advanced when doctors find it. 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 vary in size, and they have certain types of proteins, called CD4 or CD8, on their surface. It is treated with chemotherapy. Researchers are studying many new drugs in clinical trials to treat this subtype. Bone marrow transplantation may sometimes be an option.

Angioimmunoblastic T-cell lymphoma. This is an aggressive form of lymphoma with specific symptoms:

  • Enlarged, often tender, lymph nodes

  • Fever

  • Weight loss

  • Rash

  • High levels of immunoglobulins in the blood

Patients with angioimmunoblastic lymphoma have lowered immune system functions, so infections are also common. Doctors identify this type of lymphoma by what it looks like under a microscope and by certain proteins found in the tumor cells. It is treated like other aggressive lymphomas.

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 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 interferon and zidovudine (Retrovir) help some patients. Allogenic (ALLO) bone marrow transplantation may be the best approach for treatment of this type of lymphoma in people whose disease is under control after chemotherapy.

Extranodal NK/T-cell lymphoma, nasal type. This is an aggressive type of lymphoma that is very rare in the United States and Europe in general, 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 gastrointestinal tract, skin, the testicles, or other areas in the body. Radiation therapy in combination with chemotherapy is an important part of the treatment for disease that involves the nasal/sinus area. This subtype responds well to chemotherapy with asparaginase (Elspar), and some people may benefit from a bone marrow transplant.

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. Some people with this subtype have celiac disease or a history of gluten intolerance. High-dose chemotherapy may be used to treat the disease.

Hepatosplenic T-cell lymphoma. This is an aggressive form of peripheral T-cell lymphoma that involves the liver and spleen. The disease occurs most often in teenaged and young men. It is usually managed with chemotherapy followed by ALLO bone marrow transplantation.

Subcutaneous panniculitis-like T-cell lymphoma. This is a form of peripheral T-cell lymphoma that is similar to hepatosplenic T-cell lymphoma (see above). The disease involves the tissue under the skin and is often first diagnosed as panniculitis, which is 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. Mycosis fungoides can be managed with topical medications, controlled exposure to specialized radiation in the form of lights or radiation therapy, and systemic treatments, such as chemotherapy or targeted therapy. This type of NHL usually cannot be cured, but it is often manageable.

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

The next section in this guide is Stages. It explains the system doctors use to describe the extent of the disease. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Stages

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will learn about how doctors describe lymphoma’s location and spread. This is called the stage. Use the menu to see other pages.

Staging is a way of describing 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 find out 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:

  • How many cancerous lymph node areas there are

  • Where the cancerous lymph nodes are: regional (in the same area of the body) or distant (in other parts of the body)

  • If the cancerous lymph nodes are on 1 or both sides of the diaphragm, the thin muscle under the lungs and heart that separates the chest from the abdomen

  • If 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 I, II, III, or IV (1 through 4). This staging system is helpful for the most common subtypes of lymphoma. For other subtypes, the disease has often spread throughout the body by the time 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 can often be treated successfully.

  • Stage I: Either of these conditions applies:

    • The cancer is found in 1 lymph node region (stage I).

    • The cancer has invaded 1 extralymphatic organ or site (identified using the letter “E”) but not any lymph node regions (stage IE).

  • Stage II: Either of these conditions:

    • The cancer is in 2 or more lymph node regions on the same side of the diaphragm (stage II).

    • The cancer involves 1 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-IV: There is cancer in lymph node areas on both sides of the diaphragm (stage III), or the cancer has spread throughout the body beyond the lymph nodes (stage IV). Lymphoma most often spreads to the liver, bone marrow, or lungs. Stage III-IV lymphomas are common, still very treatable, and often curable, depending on the NHL subtype. Stage III and stage IV are now considered a single category because they have the same treatment and prognosis.

  • Progressive/refractory: If the cancer grows 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/relapsed: 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. This is also called relapsed NHL.

The original source for this material is Cheson BD, Fisher RI, Barrington SF, et al.: Recommendations for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma—the Lugano Classification, published in the Journal of Clinical Oncology, September 20, 2014; vol. 32, no. 27: 3059–3067.

International Prognostic Index

In addition to stage, a scale called the International Prognostic Index (IPI) is important in determining the prognosis of aggressive lymphomas. Prognosis is the chance of recovery. Each type of NHL has specific criteria as a part of the IPI. Patients are classified into low-risk or high-risk groups depending on several factors, including:

  • Age 60 or older

  • Stage III-IV disease

  • Blood test results showing higher-than-normal levels of lactate dehydrogenase (LDH), an enzyme found in the blood

  • Lower overall health, known as performance status (see below)

  • Cancer in more than 1 organ or site outside the lymph node region

For people with follicular lymphoma, doctors consider the hemoglobin level, which is a part of the blood, the number of lymph node groups involved, LDH level, stage, and age.

Doctors use these factors to estimate the prognosis of a lymphoma. For incurable lymphoma, they help predict how aggressive the lymphoma might be.

Functional status

To determine someone’s prognosis, the doctor may also test how well they are able to function and carry out daily activities by using a functional assessment scale. The Eastern Cooperative Oncology Group (ECOG) Performance Status or the Karnofsky Performance Scales (KPS) are 2 of those scales.

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

  1. Fully active, able to carry on all pre-disease performance without restriction

  2. Restricted in physically strenuous activity but able to walk and carry out light work while standing or sitting, such as light house work or office work

  3. Able to walk and capable of all self-care but unable to carry out any work activities; up and about for more than 50% of waking hours

  4. Capable of only limited self-care; confined to bed or chair for more than 50% of waking hours

  5. Completely disabled; cannot carry out any self-care; totally confined to bed or chair

  6. 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 out 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 in this guide is Types of Treatment. Use the menu to choose a different section to read in this guide.

Lymphoma - Non-Hodgkin - Types of Treatment

Approved by the Cancer.Net Editorial Board, 08/2019

ON THIS PAGE: You will learn about the different types of treatments doctors use for people with NHL. Use the menu to see other pages.

This section explains the types of treatments that are the standard of care for NHL. “Standard of care” means the best treatments known. When making treatment plan decisions, you are encouraged to consider clinical trials as an option. A clinical trial is a research study that tests a new approach to treatment. Doctors want to learn whether the new treatment is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Clinical trials are an option to consider for treatment and care for all stages of cancer. Your doctor can help you consider all your treatment options. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

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. Cancer care teams include a variety of other health care professionals, such as physician assistants, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

There are 4 main treatments for NHL:

  • Chemotherapy

  • Radiation therapy

  • Immunotherapy

  • Targeted therapy

Often, patients receive a combination of these treatments. Occasionally, the doctor and patient may consider surgery or bone marrow/stem cell transplantation.

Descriptions of the common types of treatments used for NHL are described below. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

Treatment options and recommendations depend on several factors, including:

  • The type and stage of NHL

  • Possible side effects

  • The patient’s preferences and overall health

Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment. These types of talks are called "shared decision making." Shared decision making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision making is particularly important for NHL because there are different treatment options. Learn more about making treatment decisions.

Watchful waiting

Some people 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. This is called watchful waiting, or sometimes called watch-and-wait or active surveillance. During watchful waiting, doctors closely monitor patients 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 people with indolent lymphoma, watchful waiting does not affect the chances of survival, but regular and careful follow-up care is recommended.

Therapies using medication

Systemic therapy is the use of medication to destroy cancer cells. This type of medication is given through the bloodstream to reach cancer cells throughout the body. Systemic therapies are generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication, or a hematologist, a doctor who specializes in treating blood disorders. A medical oncologist or hematologist is most often the primary cancer specialist for people with lymphoma.

Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

The types of systemic therapies used for NHL include:

  • Chemotherapy

  • Targeted therapy

  • Immunotherapy

Each of these types of therapies is discussed below in more detail. A person may receive 1 type of systemic therapy at a time or a combination of systemic therapies given at the same time. They can also be given as part of a treatment plan that includes radiation therapy.

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. It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications. Learn more about your prescriptions by using searchable drug databases.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. It is the main treatment for NHL.

A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. A patient may receive 1 drug at a time or a combination of different drugs given at the same time. The stage and type of NHL determines which chemotherapy is used. The most common chemotherapy combination for the first treatment of aggressive NHL is called CHOP and contains 4 medications:

  • Cyclophosphamide (available as a generic drug)

  • Doxorubicin (available as a generic drug)

  • Prednisone (multiple brand names)

  • Vincristine (Vincasar)

For patients with B-cell lymphoma, adding an anti-CD20 monoclonal antibody, such as rituximab or obinutuzumab, to CHOP works better than using CHOP alone (see “Targeted therapy,” below). There are other common combinations of chemotherapy regimens, including:

  • BR, which includes bendamustine (Treanda) and rituximab

  • Combinations using fludarabine (available as a generic drug)

  • R-CVP (cyclophosphamide, prednisone, rituximab, and vincristine)

The side effects of chemotherapy depend on the individual drug and the dose used. They can include fatigue, temporary lowering of blood counts, risk of infection, nausea and vomiting, hair loss, loss of appetite, rash, and diarrhea. These side effects can be managed during treatment and usually go away after treatment is finished.

Chemotherapy may also cause long-term side effects, also called late effects. People with lymphoma may also have concerns about if or how their treatment may affect their sexual health and fertility. Talk with the members of the health care team about these topics before treatment begins. Learn more about late effects of treatment.

Learn more about the basics of chemotherapy.

Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells.

Not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

Talk with your doctor about possible side effects for a specific medication and how they can be managed.

Monoclonal antibodies

For NHL, monoclonal antibodies are the main form of targeted therapy used in the treatment plan. A monoclonal antibody recognizes and attaches to a specific protein and does not affect cells that do not have that protein. A monoclonal antibody called rituximab is used to treat many different types of B-cell NHL. Rituximab works by targeting a molecule called CD20 that is located on the surface of all B cells and B-cell NHL. When the antibody attaches to this molecule, the patient’s immune system is activated to destroy some lymphoma cells or to make lymphoma cells more susceptible to being destroyed by chemotherapy.

Although the antibody may work 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 lymphoma to increase the length of the remission. There are 3 other monoclonal antibodies against CD20 that are approved by the FDA for use in lymphomas: obinutuzumab (Gazyva), ofatumumab (Arzerra), rituximab-abbs (Truxima), and rituximab-pvvr (Ruxience). Rituximab-abbs and rituximab-pvvr are called biosimilars, which means they function in a way similar to rituximab (Rituxan). Learn more about biosimilars.

Brentuximab vedotin (Adcetris) is another type of monoclonal antibody, called an antibody-drug conjugate. Antibody-drug conjugates attach to targets on cancer cells and then release a small amount of chemotherapy or other toxins directly into the tumor cells. Brentuximab vedotin combined with chemotherapy is approved to treat adults with certain types of peripheral T-cell lymphoma, such as systemic anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphoma, not otherwise specified, as long as they express the CD30 protein. The drug was previously approved for people with Hodgkin lymphoma who did not benefit from or were unable to have a bone marrow/stem cell transplant and for preventive treatment following a bone marrow transplant for higher-risk Hodgkin lymphoma. Research on the benefits of other newer monoclonal antibodies for lymphoma is ongoing.

Polatuzumab vedotin-piiq (Polivy) is a monoclonal antibody that targets CD79b. Like brentuximab vedotin, it is also an antibody-drug conjugate. Polatuzumab is used in combination with bendamustine and rituximab to treat DLBCL that has come back after at least 2 other treatments.

Radiolabeled antibodies are monoclonal antibodies with radioactive particles attached. The particles are designed to focus the radiation directly to the lymphoma cells. 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).

Talk with your doctor about possible side effects for a specific medication and how they can be managed.

Kinase inhibitors (updated 12/2019)

Kinase inhibitors are another type of targeted therapy used to treat NHL.

Acalabrutinib (Calquence) targets the Bruton’s tyrosine kinase pathway. It is approved to treat adults with mantle cell lymphoma who have received at least 1 other treatment. It is also approved to treat adults with small lymphocytic lymphoma, which is the same disease as chronic lymphocytic leukemia. The most common side effects of acalabrutinib are headache, diarrhea, muscle and join pain, upper respiratory tract infection, and bruising.

Copanlisib (Aliquopa) targets the phosphoinositide 3-kinase (PI3K) pathway. It is used to treat adults with follicular lymphoma that has come back after treatment with at least 2 previous therapies. The common side effects of copanlisib include high blood sugar, diarrhea, fatigue, high blood pressure, low white blood cell count, nausea, lung infections, and low blood platelet count.

Duvelisib (Copiktra) also targets the PI3K pathway. It is used to treat adults with small lymphocytic lymphoma that has not been stopped by at least 2 previous therapies. This targeted therapy is also used to treat chronic lymphocytic leukemia. The common side effects of duvelisib include diarrhea, intestinal problems, low white blood cell count, rash, fatigue, pain, cough, nausea, respiratory infection, pneumonia, pain, and anemia.

Ibrutinib (Imbruvica) targets the Bruton’s tyrosine kinase pathway. This drug is approved to treat several B-cell lymphomas, including mantle cell lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma, as well as chronic lymphocytic leukemia and Waldenström’s macroglobulinemia. Common side effects of ibrutinib include diarrhea, muscle and bone pain, rash, nausea, bruising, tiredness, and, less commonly, bleeding, irregular heartbeat (atrial fibrillation), or fever.

Zanubrutinib (Brukinsa) is another Bruton’s tyrosine kinase inhibitor. It is approved to treat mantle cell lymphoma in people who have received at least 1 previous therapy. The common side effects of zanubrutinib are lowered white blood cell counts, lowered platelet count, upper respiratory tract infection, lowered hemoglobin levels, rash, bruising, diarrhea and cough.

Immunomodulatory drugs

Immunomodulatory drugs modulate, or influence, how the body's immune system responds or works. Lenalidomide (Revlimid) is a thalidomide analog used to treat follicular lymphoma and mantle cell lymphoma that have not been stopped by other treatments. Lenalidomide is also used to treat multiple myeloma and myelodysplastic syndromes.

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.

In chimeric antigen receptor (CAR) T-cell therapy, some T cells are removed from a patient’s blood. Then, the cells are changed in a laboratory so they have specific proteins called receptors. The receptors allow those T cells to recognize the cancer cells. The changed T cells are grown in large numbers in the laboratory and returned to the patient’s body. Once there, they seek out and destroy cancer cells.

Axicabtagene ciloleucel (Yescarta) is a CAR T-cell therapy that is approved to treat patients with DLBCL who have received at least 2 previous types of treatment. Tisagenlecleucel (Kymriah) is another CAR T-cell therapy that is approved for the treatment of refractory B-cell lymphoma, including DLBCL, after 2 previous systemic treatments or more. Further CAR T-cell therapies are in development and being studied in clinical trials.

Checkpoint inhibitors block specific pathways to stop or slow the growth of cancer. The PD-1 pathway is a target for several checkpoint inhibitors. One of these, pembrolizumab (Keytruda), can be used to treat primary mediastinal large B-cell lymphoma that has not been stopped by at least 2 other treatments.

Different types of immunotherapy can cause different side effects. Common side effects include skin reactions, flu-like symptoms, diarrhea, and weight changes. Talk with your doctor about possible side effects for the immunotherapy recommended for you. Learn more about the basics of immunotherapy.

Radiation therapy

Radiation therapy is the use of high-energy x-rays, electrons, or protons to destroy cancer cells. 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, or schedule, usually consists of a specific number of treatments given over a set period of time.

Radiation therapy is usually given after or in addition to chemotherapy, depending on the NHL subtype. It is most often given to people who have localized lymphoma, which means that it involves only 1 or 2 adjacent areas, or to people who have a lymph node that is particularly large, usually more than 7 to 10 centimeters across. It may also be given for the treatment of pain or in very low doses (just 2 treatments) to people with advanced disease who have localized symptoms that can be relieved using radiation therapy.

General side effects from radiation therapy may include fatigue and nausea. Most side effects are related to the region of the body receiving radiation. These side effects may include mild skin reactions, dry mouth, temporary hair loss, or loose bowel movements. People who have had radiation therapy directed at the chest may experience lung inflammation called pneumonitis. People who had radiation therapy directed at the bones may experience low blood counts. Talk with your doctor about what you can expect regarding side effects and how they can be managed.

Most side effects go away soon after treatment is finished, but radiation therapy may also cause late effects, such as second cancers or damage to the heart and blood vessels if they were within the field of radiation. Sexual problems and infertility may occur after radiation therapy to the pelvis. Before treatment begins, talk with your doctor about possible sexual and fertility-related side effects of your treatment and the available options for preserving fertility for both men and women.

Learn more about the basics of radiation therapy.

Bone marrow transplantation/stem cell transplantation

A bone marrow transplant is a medical procedure in which bone marrow or peripheral blood cells containing highly specialized cells, called hematopoietic stem cells, are used as part of a treatment plan. Hematopoietic stem cells are blood-forming cells found in the bloodstream and the bone marrow. This procedure is also called a stem cell transplant. This is because stem cells collected from the blood are typically being transplanted, not cells from the actual bone marrow tissue.

Transplantation is considered an aggressive treatment. It is generally used only for people with NHL whose disease is progressive or recurrent (see Stages). For some NHL subtypes, such as mantle cell lymphoma and some T-cell lymphomas, doctors may recommend transplantation as part of the initial treatment plan to prevent recurrence.

Before recommending transplantation, the doctor will talk with you about the risks of this treatment. Doctors also consider several other factors, such as the type of NHL, results of any previous treatment, and your age and general health. It is important to talk with an experienced doctor at a specialized transplant center about the risks and benefits of this treatment.

There are 2 types of bone marrow transplantation, depending on the source of the replacement blood stem cell:

  • Allogeneic (ALLO). ALLO transplantation uses donated stem cells from a healthy individual, ideally a sibling or matched unrelated donor. Treatment includes immunochemotherapy, radiation therapy, or immunotherapy plus “graft versus lymphoma” activity, which is where the donor cells recognize and destroy the patient’s lymphoma cells. ALLO transplantation presents higher risks than AUTO transplantation, including graft-versus-host disease, which is when donor cells damage the patient’s tissues or organs.

  • Autologous (AUTO). AUTO transplantation uses the patient’s own stem cells after high-dose chemotherapy. In AUTO transplantation, the goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body using high doses of chemotherapy, immunotherapy, and/or radiation therapy. The AUTO stem cells are returned to the patient’s body after the high-dose therapy is completed. The AUTO stem cells then work to create healthy bone marrow.

Side effects of a bone marrow transplant depend on the type of transplant, your general health, and other factors. Learn more about the basics of stem cell and bone marrow transplantation.

Physical, emotional, and social effects of cancer

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer 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, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative care options.

During treatment, your health care team may ask you to answer questions about your symptoms and side effects and to describe each problem. Be sure to tell the health care team if you are experiencing a problem. This helps the health care team treat any symptoms and side effects as quickly as possible. It can also help prevent more serious problems in the future.

Learn more about the importance of tracking side effects in another part of this guide. Learn more about palliative care in a separate section of this website.

Remission and the chance of recurrence

A complete remission is when lymphoma cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED. Partial remission is when the lymphoma has regressed by more than 50% from its pretreatment state but can still be detected.

A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. While many remissions are permanent, it is important to talk with your doctor about the possibility of the disease returning. Understanding your 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 returns after the original treatment, 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 new cycle of testing will begin again to learn as much as possible about the recurrence. In most cases, another tissue biopsy is needed to prove that the lymphoma has not changed or transformed into a more aggressive subtype. After this testing is done, you and your doctor will talk about the treatment options.

Treatment for recurrent NHL depends on 3 factors:

  • Where the cancer is and whether it has transformed into a more aggressive subtype

  • Type(s) of treatment given before

  • The patient’s overall health

Often the treatment plan will include the treatments described above, such as chemotherapy, radiation therapy, targeted therapy, immunotherapy, or bone marrow/stem cell transplantation. However, they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat recurrent NHL. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

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

Progressive NHL

Some people with NHL may not experience a complete remission and will have small amounts of residual disease that is stable. Or, they will have residual disease that is actively growing despite treatment. If there is a small amount of residual disease that is stable, some people with indolent NHL may be observed with watchful waiting for a period of time or be treated with targeted therapy or other drugs. Radiation therapy to the local area may also be a possibility. 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 will begin again.

It is important to understand that remission is not always possible in some indolent lymphomas. However, some people can be safely monitored even if there is leftover disease. This is possible as long as there are no symptoms and the lymphoma has not affected blood counts or other organs.

If there is residual disease that is growing despite active treatment, it is called "refractory NHL," see below.

Refractory NHL

If standard treatments stop working well for NHL or the lymphoma comes back within 6 months after 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 chosen treatment plan. This discussion may include clinical trials.

Treatment options for refractory NHL depend on 4 factors:

  • Where the cancer is

  • The lymphoma subtype

  • The type of treatment given before

  • The patient’s overall health

The doctor may suggest chemotherapy, immunotherapy, bone marrow/stem cell transplantation, or a clinical trial. Palliative care will also be important to help relieve symptoms and side effects.

For most people, a diagnosis of refractory NHL is very stressful and, at times, difficult to bear. You and your family are encouraged to talk about how you fell 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 does not work

Recovery from NHL is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and for many people, advanced cancer is difficult to discuss. However, people with advanced NHL, especially those with indolent lymphoma, 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 health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

People who have advanced cancer and who are expected to live less than 6 months may want to consider 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 talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment can make staying at home a workable option for many families. Learn more about advanced cancer 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 loss.

The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. Use the menu to choose a different section to read in this guide.

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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. Use the menu to see other pages.

What are clinical trials?

Doctors and scientists are always looking for better ways to care for people with NHL. To make scientific advances, doctors create research studies involving volunteers, called clinical trials. In fact, every drug that is now approved by the U.S. Food and Drug Administration (FDA) was tested in clinical trials.

Clinical trials are used for all types and stages of NHL. Many focus on new treatments to learn if a new treatment is safe, effective, and possibly better than the existing treatments. These types of studies evaluate new drugs, different combinations of treatments, new approaches to radiation therapy or surgery, and new methods of treatment.

People who participate in clinical trials can be some of the first to get a treatment before it is available to the public. However, there are some risks with a clinical trial, including possible side effects and the chance that the new treatment may not work. People are encouraged to talk with their health care team about the pros and cons of joining a specific study.

Some clinical trials study new ways to relieve symptoms and side effects during treatment. Others study ways to manage the late effects that may happen a long time after treatment. Talk with your doctor about clinical trials for symptoms and side effects.

Deciding to join a clinical trial

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

Insurance coverage and the costs of clinical trials differ by location and by study. In some programs, some of the expenses from participating in the clinical trial are reimbursed. In others, they are not. It is important to talk with the research team and your insurance company first to learn if and how your treatment in a clinical trial will be covered. Learn more about health insurance coverage of clinical trials.

Sometimes people have concerns that, in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill.” When used, placebos are usually combined with standard treatment in most cancer clinical trials. 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.

Patient safety and informed consent

To join a clinical trial, people must participate in a process known as informed consent. During informed consent, the doctor should:

  • Describe all of the treatment options so that the person understands how the new treatment differs from the standard treatment.

  • List all of the risks of the new treatment, which may or may not be different than the risks of standard treatment.

  • Explain what will be required of each person in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.

Clinical trials also have certain rules called “eligibility criteria” that help structure the research and keep patients safe. You and the research team will carefully review these criteria together.

People who participate in a clinical trial may stop participating at any time for personal or medical reasons. Reasons 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 people 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 they choose to leave the clinical trial before it ends.

Finding a clinical trial

Research through clinical trials is ongoing for all types of cancer. For specific topics being studied for NHL, learn more in the Latest Research section.

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.

PRE-ACT, Preparatory Education About Clinical Trials

In addition, you can find a free video-based educational program about cancer clinical trials in another section of this website.

The next section in this guide is Latest Research. It explains areas of scientific research for NHL. Use the menu to choose a different section to read in this guide.

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ON THIS PAGE: You will read about the scientific research being done to learn more about NHL and how to treat it. Use the menu to see other pages.

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 best diagnostic and treatment options for you.

  • Gene profiling. Scientists are learning more about the genetics and the specific role that gene changes, called mutations, have in the development of cancer. As a result, they are better able to classify and diagnose subtypes of NHL. These gene profiling methods can help estimate the prognosis for people with certain types of lymphoma, and these tests are mostly used in lymphoma research. However, in the next few years, it is likely that treatments will be designed to target specific genetic changes.

  • Immunotherapy. There is ongoing research to change healthy (not cancerous) T cells so that they recognize and eliminate lymphoma cells, called CAR T-cell therapy. As explained in Types of Treatment, there are 2 approved CAR T-cell therapies for the treatment of DLBCL, and others are being tested in clinical trials.

  • Targeted therapies. As described in Types of Treatment, there are many targeted treatments approved to treat lymphoma. Many other targeted therapies are being studied in clinical trials. Those treatments include BCL-2 inhibitors and aurora kinase inhibitors.

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

  • Improving chemotherapy. Different combinations of chemotherapy and different chemotherapy schedules, sometimes including antibodies or radiolabeled antibodies, are being studied in clinical trials. Researchers are evaluating many new drugs that work differently from standard chemotherapy.

  • Bone marrow transplantation/stem cell transplantation. The use of different types of bone marrow transplantation is also being tested for people with newly diagnosed disease and for those who have had a recurrence after the first treatment. Those types include including allogeneic transplants or reduced-intensity transplants, also called mini-allogeneic or nonablative transplants. For many types of lymphoma, the best way to use transplantation is still uncertain and is being studied in clinical trials. Learn more about bone marrow transplantation.

  • Palliative care/supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current NHL treatments to improve comfort and quality of life for patients.

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 in this guide is Coping with Treatment. It offers some guidance in how to cope with the physical, emotional, social, and financial changes that cancer and its treatment can bring. Use the menu to choose a different section to read in this guide.

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ON THIS PAGE: You will learn more about coping with the physical, emotional, social, and financial effects of cancer and its treatment. Use the menu to see other pages.

Every cancer treatment can cause side effects or changes to your body and how you feel. For many reasons, people do not experience the same side effects even when they are given the same treatment for the same type of cancer. This can make it hard to predict how you will feel during treatment.

As you prepare to start cancer treatment, it is normal to fear treatment-related side effects. It may help to know that your health care team will work to prevent and relieve side effects. Doctors call this part of cancer treatment “palliative care” or "supportive care." It is an important part of your treatment plan, regardless of your age or the stage of disease.

Coping with physical side effects

Common physical side effects from each treatment option for NHL are listed in the Types of Treatment section. Learn more about side effects of cancer and its treatment, along with ways to prevent or control them. Changes to your physical health depend on several factors, including the type and stage of NHL, the length and dose of treatment, and your general health.

Talk with your health care team regularly about how you are feeling. It is important to let them know about any new side effects or changes in existing side effects. If they know how you are feeling, they can find ways to relieve or manage your side effects to help you feel more comfortable and potentially keep any side effects from worsening.

You may find it helpful to keep track of your side effects so it is easier to explain any changes with your health care team. Learn more about why tracking side effects is helpful.

Sometimes, physical side effects can last after treatment ends. Doctors call these long-term side effects. They call side effects that occur months or years after treatment late effects. Treating long-term side effects and late effects is an important part of survivorship care. Learn more by reading the Follow-up Care section of this guide or talking with your doctor.

Coping with emotional and social effects

You can have emotional and social effects as well as physical effects after a cancer diagnosis. This may include dealing with difficult emotions, such as sadness, anxiety, or anger, or managing your stress level. Sometimes, people find it difficult to express how they feel to their loved ones. Some have found that talking to an oncology social worker, counselor, or member of the clergy can help them develop more effective ways of coping and talking about cancer.

You can also find coping strategies for emotional and social effects in a separate section of this website. This section includes many resources for finding support and information to meet your needs.

Coping with financial effects

Cancer treatment can be expensive. It is often a big source of stress and anxiety for people with cancer and their families. In addition to treatment costs, many people find they have extra, unplanned expenses related to their care. For some people, the high cost of medical care stops them from following or completing their cancer treatment plan. This can put their health at risk and may lead to higher costs in the future. Patients and their families are encouraged to talk about financial concerns with a member of their health care team. Learn more about managing financial considerations in a separate part of this website.

Caring for a loved one with cancer

Family members and friends often play an important role in taking care of a person with NHL. This is called being a caregiver. Caregivers can provide physical, practical, and emotional support to the patient, even if they live far away.

Caregivers may have a range of responsibilities on a daily or as-needed basis, including:

  • Providing support and encouragement

  • Talking with the health care team

  • Giving medications

  • Helping manage symptoms and side effects

  • Coordinating medical appointments

  • Providing a ride to and from appointments

  • Assisting with meals

  • Helping with household chores

  • Handling insurance and billing issues

Learn more about caregiving.

Talking with your health care team about side effects

Before starting treatment, talk with your doctor about possible side effects. Ask:

  • Which side effects are most likely?

  • When are they likely to happen?

  • What can we do to prevent or relieve them?

Be sure to tell your health care team about any side effects that happen during treatment and afterward, too. Tell them even if you do not think the side effects are serious. This discussion should include physical, emotional, and social effects of cancer.

Also, ask how much care you may need at home and with daily tasks during and after treatment. This can help you make a caregiving plan. Create a caregiving plan with this 1-page fact sheet that includes an action plan to help make caregiving a team effort. This free fact sheet is available as a PDF, so it is easy to print out.

Looking for More on How to Track Side Effects?

Cancer.Net offers several resources to help you keep track of your symptoms and side effects. Please note that these links will take you to other sections of Cancer.Net:

  • Cancer.Net Mobile: The free Cancer.Net mobile app allows you to securely record the time and severity of symptoms and side effects.

  • ASCO Answers Managing Pain: Get this 36-page booklet about the importance of pain relief that includes a pain tracking sheet to help patients record how pain affects them. The free booklet is available as a PDF, so it is easy to print out.

  • ASCO Answers Fact Sheets: Read 1-page fact sheets on diarrhea and rash that provide a tracking sheet to record the timing and severity of the side effect. These free fact sheets are available as a PDF, so they are easy to print out.

The next section in this guide is Late Effects of Treatment. It describes side effects that may develop months or years after treatment has ended. Use the menu to choose a different section to read in this guide.

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ON THIS PAGE: You will find out more about the late effects of treatment, which are side effects that can occur long after treatment for NHL has ended. Use the menu to see other pages.

People who have been treated for lymphoma have an increased risk of developing other diseases or conditions later in life. This is because cancer medications and radiation therapy can cause permanent damage to healthy parts of the body. Treatments have improved in the last 30 years, and now people who are treated for lymphoma recently are less likely to experience late effects. However, there is still some risk. Therefore, it is important for people to receive follow-up care to watch for the following late effects.

  • People who have received radiation therapy to the pelvis, high doses of cyclophosphamide, and high-dose chemotherapy for bone marrow transplantation are at risk for infertility. Learn more about fertility concerns and preservation for men and women.

  • All survivors of NHL have a higher risk 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 received radiation therapy to the chest before age 35 have an increased risk of developing breast cancer.

  • People who have received doxorubicin-based chemotherapy or radiation therapy to the chest may be at higher risk for developing heart problems, such as heart failure, valvular disease, pericarditis, and rhythm abnormalities.

  • Adults who have received radiation therapy to the chest area may be at risk for lung damage and shortness of breath later in life.

  • People who have received radiation therapy to the neck have an increased risk of having low levels of thyroid hormones later in life.

  • People who have received a bone marrow transplant may be at higher risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Learn more about late effects of cancer treatment.

The next section in this guide is Follow-up Care. It explains the importance of checkups after cancer treatment is finished. Use the menu to choose a different section to read in this guide.

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ON THIS PAGE: You will read about your medical care after cancer treatment is completed and why this follow-up care is important. Use the menu to see other pages.

Care for people diagnosed with cancer does not end when active treatment has finished. Your health care team will continue to check that the cancer has not come back, manage any side effects, and monitor your overall health. This is called follow-up care.

Your follow-up care may include regular physical examinations, medical tests, or both. Doctors want to keep track of your recovery in the months and years ahead. For people treated for an aggressive lymphoma, visits are most frequent in the first 3 years following the end of treatment. For many aggressive lymphomas, there are very few recurrences after 5 years, and some oncologists stop routine follow-up visits at this time. However, these people should continue routine follow-up with their primary care physician to watch for late effects of treatment.

For slow-growing, or indolent, lymphomas, follow-up visits may continue throughout the person’s lifetime. Most doctors will see a person treated for an indolent lymphoma between 2 and 4 times per year for a physical examination and blood tests. During this time, doctors may also monitor the disease with CT scans or PET scans if there are any abnormal test or exam results or if symptoms are getting worse.

Although CT scans and PET scans are very important tools for determining the disease’s response to treatment and monitoring for recurrence, there is debate over when and how often scans should be used. As discussed in Diagnosis, both of these imaging tests expose the person to a small amount of radiation. An integrated (combined) PET-CT scan causes more radiation exposure than either alone.

Most doctors agree that performing routine scans, particularly when the person has no symptoms, may be exposing patients to unnecessary radiation. However, there are few recommendations 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 used.

Learn more about the importance of follow-up care.

Watching for recurrence

One goal of follow-up care is to check for a recurrence, which means that the cancer has come back. Cancer recurs because small areas of cancer cells may remain undetected in the body. Over time, these cells may increase in number until they show up on test results or cause signs or symptoms. During follow-up care, a doctor familiar with your medical history can give you personalized information about your risk of recurrence. Your doctor will ask specific questions about your health. Some people may have blood tests or imaging tests done as part of regular follow-up care, but testing recommendations depend on several factors, including the type and stage of cancer originally diagnosed and the types of treatment given.

The anticipation before having a follow-up test or waiting for test results can add stress to you or a family member. This is sometimes called “scan-xiety.” Learn more about how to cope with this type of stress.

Managing long-term and late side effects

Most people expect to experience side effects when receiving treatment. However, it is often surprising to survivors that some side effects may linger beyond the treatment period. These are called long-term side effects. Other side effects called late effects may develop months or even years afterwards. Long-term and late effects can include both physical and emotional changes (see Late Effects of Treatment).

Talk with your doctor about your risk of developing such side effects based on the type of cancer, your individual treatment plan, and your overall health. If you had a treatment known to cause specific late effects, you may have certain physical examinations, scans, or blood tests to help find and manage them.

Keeping personal health records

You and your doctor should work together to develop a personalized follow-up care plan. Be sure to discuss any concerns you have about your future physical or emotional health. ASCO offers forms to help keep track of the cancer treatment you received and develop a survivorship care plan when treatment is completed.

This is also a good time to talk with your doctor about who will lead your follow-up care. As mentioned above, some survivors continue to see their oncologist, while others transition back to the care of their family doctor or another health care professional. This decision depends on several factors, including the type and stage of cancer, side effects, health insurance rules, and your personal preferences.

If a doctor who was not directly involved in your cancer care will lead your follow-up care, be sure to share your cancer treatment summary and survivorship care plan forms with him or her and with all future health care providers. Details about your cancer treatment are very valuable to the health care professionals who will care for you throughout your lifetime.

The next section in this guide is Survivorship. It describes how to cope with challenges in everyday life after a cancer diagnosis. Use the menu to choose a different section to read in this guide.

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ON THIS PAGE: You will read about how to cope with challenges in everyday life after a cancer diagnosis. Use the menu to see other pages.

What is survivorship?

The word “survivorship” means different things to different people. Common definitions include:

  • Having no signs of cancer after finishing treatment.

  • Living with, through, and beyond cancer. According to this definition, cancer survivorship begins at diagnosis and includes people who continue to have treatment over the long term, to either reduce the risk of recurrence or to manage chronic disease.

Survivorship is one of the most complicated parts of having cancer. This is because it is different for everyone.

Survivors may experience a mixture of strong feelings, including joy, concern, relief, guilt, and fear. Some people say they appreciate life more after a cancer diagnosis and have gained a greater acceptance of themselves. Others become very anxious about their health and uncertain about coping with everyday life.

Survivors may feel some stress when their frequent visits to the health care team end after completing treatment. Often, relationships built with the cancer care team provide a sense of security during treatment, and people miss this source of support. This may be especially true when new worries and challenges surface over time, such as any late effects of treatment, emotional challenges including fear of recurrence, sexuality and fertility concerns, and financial and workplace issues.

Every survivor has individual concerns and challenges. With any challenge, a good first step is being able to recognize your fears and talk about them. Effective coping requires:

  • Understanding the challenge you are facing

  • Thinking through solutions

  • Asking for and allowing the support of others

  • Feeling comfortable with the course of action you choose

Many survivors find it helpful to join an in-person support group or an online community of survivors. This allows you to talk with people who have had similar first-hand experiences. Other options for finding support include talking with a friend or member of your health care team, individual counseling, or asking for assistance at the learning resource center of the place where you received treatment.

Changing role of caregivers

Family members and friends may also go through periods of transition. A caregiver plays a very important role in supporting a person diagnosed with cancer, providing physical, emotional, and practical care on a daily or as-needed basis. Many caregivers become focused on providing this support, especially if the treatment period lasts for many months or longer.

However, as treatment is completed, the caregiver's role often changes. Eventually, the need for caregiving related to the cancer diagnosis will become much less or come to an end. Caregivers can learn more about adjusting to life after caregiving.

A new perspective on your health

For many people, survivorship serves as a strong motivator to make lifestyle changes.

People recovering from NHL are encouraged to follow established guidelines for good health, such as not smoking, limiting alcohol, eating well, and managing stress. Regular physical activity can help rebuild your strength and energy level. Your health care team can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about making healthy lifestyle choices.

It is important to have recommended medical checkups and tests (see Follow-up Care) to take care of your health. Cancer rehabilitation may be recommended. This could mean any of a wide range of services such as physical therapy, career counseling, pain management, nutritional planning, and/or emotional counseling. The goal of rehabilitation is to help people regain control over many aspects of their lives and remain as independent and productive as possible.

Talk with your health care team to develop a survivorship care plan that is best for your needs.

Looking for More Survivorship Resources?

For more information about cancer survivorship, explore these related items. Please note that these links will take you to other sections of Cancer.Net:

  • ASCO Answers Cancer Survivorship Guide: Get this 44-page booklet that helps people transition into life after treatment. It includes blank treatment summary and survivorship care plan forms. The free booklet is available as a PDF, so it is easy to print out.

  • Cancer.Net Patient Education Video: View a short video led by an ASCO expert that provides information about what comes after finishing treatment.

  • Survivorship Resources: Cancer.Net offers an entire area of this website with resources to help survivors, including those in different age groups.

The next section offers Questions to Ask the Health Care Team to help start conversations with your cancer care team. Use the menu to choose a different section to read in this guide.

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

Talking often with the health care team 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 a digital list and other interactive tools to manage your care. It may also be helpful to ask a family member or friend to come with you to appointments to help take notes.

Questions to ask after getting a diagnosis

  • 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 subspecialty boards in hematology, oncology, or radiation oncology?

  • Where in my body has the disease spread?

  • Which stage is the lymphoma? What does this mean?

  • Is my lymphoma curable? If so, what are the chances of a cure? If not, can the disease be controlled?

Questions to ask about choosing a treatment and managing side effects

  • What are my treatment options?

  • What clinical trials are available for me? Where are they located, and how do I find out more about them?

  • Why is watchful waiting sometimes appropriate? Is this an option for me?

  • Will I need surgery, therapy using medications, and/or radiation therapy?

  • What treatment plan do you recommend? Why?

  • What is the goal of each treatment? Is it to eliminate the cancer, help me feel better, or both?

  • What are the possible side effects of this treatment, both in the short term and the long term?

  • Who will be part of my health care team, and what does each member do?

  • Who will be leading my overall treatment?

  • 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 of cancer care, who can help me?

  • 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?

  • If I have questions or problems, who should I call?

Questions to ask about having therapy using medications

  • What type of treatment is recommended?

  • What is a monoclonal antibody? Is this treatment appropriate for me?

  • What is the goal of this treatment?

  • How long will it take to give this treatment?

  • What side effects can I expect during treatment?

  • Who should I contact about any side effects I experience? And how soon?

  • What are the possible long-term effects of having this treatment?

  • What can be done to relieve the side effects?

Questions to ask about having radiation therapy

  • What type of treatment is recommended?

  • What is the goal of this treatment?

  • How long will it take to give this treatment?

  • What side effects can I expect during treatment?

  • Who should I contact about any side effects I experience? And how soon?

  • What are the possible long-term effects of having this treatment?

  • What can be done to relieve the side effects?

Questions to ask about having a bone marrow/stem cell transplant

  • Which type of bone marrow transplant would you recommend? Why?

  • If I will have an ALLO transplant, how will we find a donor? What is the chance of a good match?

  • What type of treatment will I have before the transplant? Will radiation therapy be used?

  • How long will my treatment take? How long will I stay in the hospital?

  • How will a transplant affect my life? Can I work? Can I exercise and do regular activities?

  • How will we know if the transplant works?

  • What if the transplant does not work? What if the cancer comes back?

  • What are the short-term side effects that may happen during treatment or shortly after?

  • Who should I contact about any side effects I experience? And how soon?

  • What are the long-term side effects that may happen years later?

  • What tests will I need later? How often will I need them?

Questions to ask about planning follow-up care

  • What is the chance that the cancer will come back? Should I watch for specific signs or symptoms?

  • What long-term side effects or late effects are possible based on the cancer treatment I received?

  • What follow-up tests will I need, and how often will I need them?

  • Is there anything I can do to prevent a recurrence of my lymphoma?

  • How do I get a treatment summary and survivorship care plan to keep in my personal records?

  • Who will be leading my follow-up care?

  • What survivorship support services are available to me? To my family?

The next section in this guide is Additional Resources. It offers some more resources on this website beyond this guide that may be helpful to you. Use the menu to choose a different section to read in this guide.

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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. Use the menu to go back and see other pages.

Cancer.Net includes many other sections about the medical and emotional aspects of cancer 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 links to help you explore other parts of Cancer.Net:

This is the end of Cancer.Net’s Guide to Non-Hodgkin Lymphoma. Use the menu to choose a different section to read in this guide.