Non-Hodgkin Lymphoma

What is non-Hodgkin lymphoma?

Non-Hodgkin lymphoma is a group of blood cancers that usually develop in your lymphatic system. They're acquired genetic disorders. You’re not born with these disorders. Instead, they happen when genes inside certain cells mutate or change. In this case, the affected cells are B lymphocytes (B cells) or T lymphocytes (T cells) that are part of your immune system.

There are more than 70 types of non-Hodgkin lymphoma. People are living longer with these conditions thanks to new treatments, including targeted therapies. In some cases, treatments eliminate all non-Hodgkin lymphoma signs and symptoms and cure the condition. In other cases, the goal of the treatment is to put the disease into remission for as long as possible.

Are non-Hodgkin lymphomas common?

They're relatively common. In the United States, this group of conditions is the sixth most common cancer in men and people designated male at birth (DMAB) and the sixth most common cancer in women and people designated female at birth (DFAB).

The U.S. National Cancer Institute estimates that 2% of all men and people DMAB and women and people DFAB will develop some type of non-Hodgkin lymphoma in their lifetime. Non-Hodgkin lymphomas represent about 3% of all cancer-related deaths in the U.S. Worldwide, approximately 5 in 100,000 people have a type of non-Hodgkin lymphoma and about 3 in 100,000 people die from this condition.

Who is affected by these conditions?

Non-Hodgkin lymphomas typically affect people age 60 and older. They're somewhat more common in men and people DMAB than in women and people DFAB. They typically affect more people who are white than people who are Black.

How does non-Hodgkin lymphoma affect my body?

Non-Hodgkin lymphoma isn’t a single disease. There are many different types of non-Hodgkin lymphomas. These types have the same kinds of symptoms. However, each type of lymphoma may affect your body in different ways. For example, some types of non-Hodgkin lymphoma spread more quickly than other types. Some types affect organs like your spleen and liver while other types affect your skin.

Some non-Hodgkin lymphomas may affect your lymphatic system and your ability to fight infection. Your lymphatic system is a network of organs, vessels and lymph nodes that works with your immune system. Non-Hodgkin lymphomas happen when white blood cells known as lymphocytes mutate or change.

These cells include B cells, T cells and natural killer (NK) cells. The normal function of B cells is to make antibodies that fight bacteria and infections. T cells target viruses and other foreign cells and help B cells make antibodies. NK cells attack some cancer cells and viruses. Healthcare providers classify lymphomas according to the type of white blood cell in which a lymphoma starts. About 85% of all non-Hodgkin lymphomas start in B cells.

When these cells mutate, they continuously multiply, eventually becoming tumors. Since your lymphatic system touches nearly every part of your body, non-Hodgkin lymphoma frequently spreads from where it started to other areas of your body. Non-Hodgkin lymphomas may grow slowly (indolent) or spread very quickly (aggressive).

What are the most common types of aggressive non-Hodgkin lymphomas?

There are several common forms of aggressive non-Hodgkin lymphomas. These are lymphomas that progress or spread very quickly and cause more serious symptoms than indolent non-Hodgkin lymphoma. They tend to respond quickly to treatment.

Aggressive B-cell lymphomas

• Diffuse Large B-cell lymphoma (DLBCL): This is the most common type of non-Hodgkin lymphoma, accounting for about 30% of all cases in the U.S. DLBCL grows very quickly and may start in lymph nodes or in other parts of your body. Medical researchers have identified three different DLBCL subgroups. These are germinal center B-cell-like (GCB), activated B-cell-like (ABC) and unclassified. GBC and ABC have several different genetic subtypes and react to chemotherapy in different ways.
• Mantle cell lymphoma: This type happens when a B cell located in the so-called mantle zone of a lymph node mutates. It accounts for about 5% to 7% of all non-Hodgkin lymphomas and typically affects males/people DMAB age 60 and older. While mantle cell lymphoma is considered an aggressive B-cell lymphoma, there are times when it grows more slowly. This typically happens in older people who have lymphoma in their spleen and lymphoma cells in their bloodstream.
• Lymphoblastic lymphoma: This is cancer of immature lymphoblasts, which normally produce healthy lymphocytes. This non-Hodgkin lymphoma type is very similar to acute lymphoblastic leukemia (ALL).
• Burkitt lymphoma: This is one of the fastest growing forms of cancer but one with high rates of remission and cure. This lymphoma typically goes into remission after intensive chemotherapy.

Aggressive T-cell and NK lymphomas

• Peripheral T-cell lymphoma (PTCL): In this lymphoma, a group of T-cell and natural killer lymphomas develop in lymphoid tissues including your spleen, skin and gastrointestinal tract. It’s usually diagnosed in people age 60 and older. PTCL accounts for about 6% of all non-Hodgkin lymphomas in the U.S. and Europe.
• Angioimmunoblastic T-cell lymphoma (AITL): This lymphoma type typically affects people age 40 and older. Some AITL symptoms are similar to certain autoimmune disorders.
• Systemic anaplastic large cell lymphoma (ALCL):This is a rare lymphoma type. It may affect your lymph nodes and organs. There are two systemic ALCL subtypes. One affects children and young adults. The other primarily affects older adults.
• Hepatosplenic gamma/delta T-cell lymphoma: This aggressive form of peripheral T-cell lymphoma affects your liver and spleen. Men and people DMAB are more likely to develop this condition than women and people DFAB. This condition typically affects teenagers and adults under age 40.

What are the most common types of indolent non-Hodgkin lymphomas?

These lymphoma types typically grow very slowly. People who have a form of indolent non-Hodgkin lymphoma may not notice changes in their body that turn out to be symptoms of non-Hodgkin lymphoma.

Indolent B-cell lymphomas

People diagnosed with indolent lymphoma may not need immediate treatment. Healthcare providers instead may monitor your health until they determine that treatment is necessary. This is sometimes called “watchful waiting”. Existing treatments often can’t cure this condition yet are very effective. These treatments typically ease and sometimes eliminate symptoms for a long time.

• Follicular lymphoma: This lymphoma type forms in your lymph nodes, bone marrow and other organs. It’s the second most common form of non-Hodgkin lymphoma in the U.S. and Europe.
• Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Although the term CLL sounds different from the term lymphoma, CLL is similar to other indolent B-cell lymphomas. Healthcare providers use the term CLL when you have large numbers of abnormal B cells in your bloodstream. CLL is essentially the same disease as SLL, in which the abnormal B cells are primarily in your tissues and lymph nodes.
• Marginal zone lymphoma: There are three types of marginal zone lymphoma — nodal marginal lymphoma, splenic marginal zone lymphoma and extranodal marginal zone lymphoma. This last type is sometimes known as mucosa-assisted lymphoid tissue (MALT) lymphoma. MALT lymphoma affects organs other than lymph nodes including the lining of your stomach, your lungs and the structure around your eyes.
• Waldenström macroglobulinemia (lymphoplasmacytic lymphoma): This lymphoma type happens when genetic mutations change B cells that produce a particular type of antibody called IgM. Both the lymphoma cells themselves and the IgM antibody that they produce can cause specific signs and symptoms.

Indolent T-cell/NK-cell lymphomas

• Cutaneous T-cell lymphoma: This rare lymphoma type affects your skin. Mycosis fungoides and Sézary syndrome are examples of cutaneous T-cell lymphomas.

How serious are non-Hodgkin lymphomas?

These serious conditions can sometimes make your body more vulnerable to life-threatening infections, other kinds of cancer or heart disease. Data show about 3 in 100,000 people worldwide die of some type of non-Hodgkin lymphoma.

What is the survival rate of non-Hodgkin lymphomas?

Studies show that overall, 73% percent of people with these conditions are alive five years after their diagnosis. In general, people diagnosed before the condition spreads live longer than people who are diagnosed after the condition spreads.

Can children have a non-Hodgkin lymphoma?

Yes, this group of conditions can affect children. There are three common types of non-Hodgkin lymphoma in children:

• Burkitt lymphoma.
• Diffuse large B-cell lymphoma.
• Primary mediastinal B-cell lymphoma.

What causes non-Hodgkin lymphomas?

Non-Hodgkin lymphomas happen when your body produces too many leukocytes or white blood cells. Healthcare providers don’t know all the reasons why this happens. Genetic mutations that affect white blood cell growth play a part. (These are acquired genetic mutations, meaning you develop them during your lifetime instead of being born with them.) They also know people who have certain infections or problems with their immune system are more likely to develop a non-Hodgkin lymphoma.

What are the symptoms of non-Hodgkin lymphomas?

Non-Hodgkin lymphomas cause many symptoms. It’s important to remember that many of these symptoms are common and related to many conditions. Simply having these symptoms doesn’t mean you have a non-Hodgkin lymphoma. That said, you should contact your healthcare provider anytime you notice changes in your body that last for several weeks.

Here are common symptoms of non-Hodgkin lymphomas:

• Swollen lymph nodes: You may have painless swelling in your neck, armpits or groin.
• Belly (abdominal) pain or swelling: Not all belly pain is a sign of serious illness. Contact your healthcare provider if you have severe pain that doesn’t go away.
• Chest pain: This may be a symptom of a non-Hodgkin lymphoma in your lung tissues or in lymph nodes inside your chest.
• Cough: Non-Hodgkin lymphomas in your thymus or blocked lymph vessels may cause coughing. Your thymus is a small gland in your chest. Blocked blood vessels may cause fluid to gather around your lungs, making you cough.
• Trouble breathing (dyspnea):This feels like you can’t take a deep breath.
• Persistent fatigue: This is feeling much more tired than usual for at least several days and for no apparent reason.
• Unexplained fever: Often, fevers are signs your body is fighting an infection. A fever that stays above 103 F (39.5 C) for two or more hours after home treatment or lasts longer than two days may be a sign of a serious problem.
• Heavy night sweats: This is sweating so intense that it drenches your sheets.
• Unexplained weight loss: This is losing body weight without trying. Losing 10% of your total body weight over six months is a sign of unexplained weight loss.
• Feeling of fullness: This is feeling as if you’ve eaten a lot and have a full stomach even though you’re not eating a lot.

How do healthcare providers diagnose non-Hodgkin lymphomas?

Providers may use the following tests:

Blood tests

Blood tests give your healthcare provider a view of your overall health. Providers may test your blood for viruses linked to non-Hodgkin lymphoma, or for substances or other characteristics that may be signs of disease.

• Complete blood count (CBC): This test measures and counts your blood cells.
• Blood chemistry study: This test measures substances that your organs and tissues release into your bloodstream.
• Lactate dehydrogenase (LDH) levels: This test measures LDH levels. High LDH levels may be a sign of tissue damage, lymphoma or other diseases.

Imaging tests

Imaging tests give healthcare providers information about changes in your body, such as tumors.

• Computed tomography (CT) scan: CT scans make a series of detailed pictures of areas inside your body.
• Positron emission tomography (PET) scan: This test uses a small amount of radioactive tracer to detect tissues that are likely to contain cancer.
• Magnetic resonance imaging (MRI) scan: This test uses a magnet, radio waves and a computer to make a series of detailed pictures of areas inside your body.
• Ultrasound: In this procedure, high-energy sound waves (ultrasound) bounce off internal tissues or organs and make echoes. The echoes form a picture of your body tissues called a sonogram.

Other tests

• Lymph node biopsy: Providers may remove all or part of a lymph node to examine the tissue under a microscope for signs of Reed Sternberg cells.
• Immunophenotyping: This test helps diagnose specific lymphoma types. It uses antibodies to identify cancer cells based on the types of antigens or markers on the surface of the cells. (Your body makes antibodies to combat foreign substances. Antigens are substances that trigger your immune system.)
• Hepatitis B and Hepatitis C: Providers may test for hepatitis B and C markers to help plan Hodgkin lymphoma treatment. Markers are virus-specific antigens and/or antibodies. Different markers or combinations of markers show if you’ve been exposed to these viruses.
• Human immunodeficiency virus (HIV):Providers may test for HIV to help them plan treatment.

What are the stages of non-Hodgkin lymphomas?

Test results help providers with cancer staging. Providers stage cancer to develop treatment plans and estimate prognosis, or expected outcome. Here's information about non-Hodgkin lymphoma stages:

Stage I

• There's lymphoma in one lymph node area or one lymphoid organ. Your thymus, spleen and bone marrow are lymphoid organs.
• Stage IE: There’s lymphoma in just one area of a single organ outside of your lymph system.

Stage II

• There's lymphoma in two or more groups of lymph nodes on the same side of (above or below) your diaphragm. This is the band of muscle that separates your chest and belly.
• The lymphoma is part of a group of lymph nodes and is in one area of a nearby organ. In this stage, the lymphoma may also affect other lymph nodes near your diaphragm.

Stage III:

• There's lymphoma in lymph node areas on both sides of (above and below) your diaphragm.

Or:

• There's lymphoma in lymph nodes above your diaphragm and in your spleen.

Stage IV:

• There's lymphoma in at least one organ outside your lymph system, such as your bone marrow, liver or lung.

Understanding cancer staging

Cancer staging systems help healthcare providers to plan treatment and share information about your situation. Healthcare providers use stages to plan non-Hodgkin lymphoma treatment. They also evaluate risk factors to place conditions in certain categories that characterize prognosis or expected outcomes.

Some people who have cancer may be confused and intimidated by a system that describes their illness with a formula of letters and numbers or risk factors that place them in one category or another. They may even feel as if their condition’s stage or category defines who they are.

Healthcare providers understand why people may feel this way. If this is your situation, talk to your provider. They’ll be glad to answer your questions about cancer staging systems.

How do healthcare providers treat non-Hodgkin lymphoma?

There are several types of treatments for non-Hodgkin lymphoma. These treatments either kill cancer cells or keep them from dividing. Each treatment has different side effects. Here's more information:

• Watchful waiting/active surveillance: If you have a type of indolent or slow-growing non-Hodgkin lymphoma but don’t have symptoms, your provider may hold off on medications or other treatments. This is called watchful waiting or active surveillance. Providers carefully monitor your overall health so they’re ready to start treatment as soon as you have symptoms.
• Traditional systemic chemotherapy: These drugs attack cancer cells throughout your body. Most traditional chemotherapy drugs are given intravenously and sometimes have side effects such as nausea, hair loss or low numbers of normal blood cells.
• Targeted therapy: These include treatments such as monoclonal antibody therapy. This treatment uses lab-created antibodies to find and destroy specific cancer cells.
• Immunotherapy: This treatment, also called biologic therapy or biotherapy, boosts your body’s immune system. CAR-T cell therapy is an example of immunotherapy, although many healthcare providers also view monoclonal antibodies as a type of immunotherapy as well.
• Radiation therapy: This treatment includes X-rays or other types of radiation.
• Chemotherapy with stem cell transplantation: Stem cells are immature blood cells in your blood or bone marrow. In stem cell transplantation, providers may do autologous stem cell transplantation. Less frequently, they may do allogeneic stem cell transplantation.

How can I reduce my risk of developing non-Hodgkin lymphoma?

There are several risk factors linked to non-Hodgkin lymphoma. A risk factor is an activity or physical condition that increases your risk of developing a certain disease. Your risk of developing a non-Hodgkin lymphoma increases if you're:

• Older.
• A man or a person DMAB.
• White.

As explained below, you may also be at risk if you:

• Have certain medical conditions.
• Have had certain medical treatments.
• Have certain lifestyle habits.

Medical conditions

The following conditions may increase your risk:

• Autoimmune diseases: People with inflammatory bowel disease, rheumatoid arthritis, psoriasis or other rheumatologic conditions may have an increased risk of developing a non-Hodgkin lymphoma.
• HIV/AIDS: Human immunodeficiency virus (HIV) is the virus that causes acquired immune deficiency syndrome (AIDS). Having non-Hodgkin lymphoma doesn’t mean you have HIV/AIDS.
• Helicobacter pylori infection: This infection causes stomach ulcers. Repeated bouts of this infection increase your risk of developing a non-Hodgkin lymphoma.
• Human T-lymphotrophic virus Type I or Epstein-Barr virus.

Medical treatments

Some people who have had the following treatments may develop a non-Hodgkin lymphoma:

• Organ transplant: People who’ve gone through organ transplantation — including heart, lung and kidney transplantations — have increased risk of developing lymphoma. This is because they need to take anti-rejection medication that suppresses their immune systems.
• Previous treatment for non-Hodgkin lymphoma.
• Radiation therapy.

Other risk factors

You may develop a non-Hodgkin lymphoma if you:

• Work around pesticides: Some research shows people exposed to certain high levels of pesticides, such as agricultural workers, may have a slightly increased risk of non-Hodgkin lymphoma. The risk from low-level and/or periodic exposure to these substances is not certain.
• Have obesity.
• Eat a lot of meat and fats.

Do people survive non-Hodgkin lymphomas?

Yes, people who have treatment for non-Hodgkin lymphomas go into remission. Remission means they don’t have any symptoms and tests show they don’t have signs of the condition. Some people are considered to be cured because they’ve remained in remission for many years. Sometimes non-Hodgkin lymphomas come back. Studies show most aggressive non-Hodgkin lymphomas come back during the first two years after treatment, or they never come back.

It’s important to remember that not everyone diagnosed with a non-Hodgkin lymphoma ultimately dies from it, even if the condition can’t be cured.

What is the risk of relapse?

There are two reasons why your condition may come back:

• Your treatment didn’t eliminate the condition.
• Your condition went into remission and then came back or relapsed. This may happen because treatment eliminated fast-growing cells but left slow-growing cells behind.

Can my healthcare provider estimate the chance my condition will come back?

Yes, they can. For example, if you have an aggressive type of non-Hodgkin lymphoma, your healthcare provider may use the International Prognostic Index (IPI), one of several risk-scoring tools. The index is based on factors such as your age, non-Hodgkin lymphoma stage and certain blood test results.

What’s it like to live with non-Hodgkin lymphoma?

For some people, living with non-Hodgkin lymphoma means their treatment eliminated the cancer cells and they're cured. This is more common after treatment for aggressive lymphoma. Other people may have this condition for the rest of their lives. It’s important to remember that with some forms of non-Hodgkin lymphoma, many people have normal (or near normal) quality of life. It’s just as important to remember that not everyone who's diagnosed ultimately dies from it, even if the condition can’t be cured.

Living in remission

If your condition is in remission, it means treatment eliminated all signs and symptoms of non-Hodgkin lymphoma. Even so, you’ll need regular checkups so your healthcare provider can monitor your overall health and watch for relapse.

You may feel anxious because you can’t be sure you won’t get sick again. If that’s your situation, talk to your provider. They may have information to make you worry less. They may also have resources to help you manage your emotions.

Living with a non-Hodgkin lymphoma

Some people with a non-Hodgkin lymphoma will need continuous treatment. Other people may need occasional treatment. In both cases, however, these people will still have a non-Hodgkin lymphoma and will need some form of treatment for the rest of their lives.

It’s not easy to live with a chronic disease that’s likely to get worse as time goes by. If you are living with non-Hodgkin lymphoma, you may want to explore palliative care. Palliative care provides symptom relief, comfort and support to people living with serious medical conditions.

What can I do to manage my condition?

You can manage your condition in several ways. These activities won’t make your condition go away, but they may help you feel more confident about living with it:

• Eat healthy meals: Food is energy. Eating well is one way to maintain strength. Ask to speak to a nutritionist if you’d like more information or ideas about eating well.
• Rest as much as you can: You may feel worn out by chemotherapy and other treatments. Rest helps your body recover and regain strength.
• Manage your stress: It’s not easy to live with a non-Hodgkin lymphoma. You may wonder how the condition and treatment will affect your daily life. You may be worried about your prognosis. Talk to your provider if you’re spending time and emotional energy worrying about your situation. They’ll answer your questions and recommend programs, like support groups, that may help.
• Stop smoking: There’s some indication that people who smoke increase their risk of developing a non-Hodgkin lymphoma. If you smoke, ask your provider about smoking cessation programs.

When should I see my healthcare provider?

If you’re receiving treatment for non-Hodgkin lymphoma, you should contact your provider if your symptoms return or get worse.

When should I go to the emergency room?

You should go to the emergency room if you have treatment side effects that don’t subside after taking prescribed medication, are stronger than you expect or continue for a long time.

What questions should I ask my doctor?

You’ll probably have many questions as you go through diagnosis and treatment for non-Hodgkin lymphoma. Here are some questions you may want to ask your healthcare provider:

• What kind of non-Hodgkin lymphoma do I have?
• What stage is my disease?
• What treatments do you recommend?
• What are the side effects of those treatments?
• Can you cure my non-Hodgkin lymphoma?

A note from Cleveland Clinic

Newer treatments such as targeted therapy and immunotherapy are making a difference for people who have some type of non-Hodgkin lymphoma. Some people are living longer. Some people no longer have non-Hodgkin lymphoma symptoms or signs of disease. In some forms of non-Hodgkin lymphoma, many people complete treatment and go on to have normal (or nearly normal) quality of life.

Meanwhile, researchers continue to investigate genetic mutations that cause non-Hodgkin lymphoma. If you’re living with non-Hodgkin lymphoma, ask your healthcare provider about clinical trials evaluating potential treatments.