Non-Hodgkin lymphoma (NHL) is a term that refers to many, very different types of lymphoma, cancers of the lymph system. When lymphatic cells mutate (change) and grow uncontrollably, they can form tumors.
The lymph system is made up of thin tubes that branch out to all parts of the body. Its job is to fight infection and disease. The lymph system carries lymph, a colorless fluid containing lymphocytes (white blood cells). Lymphocytes fight germs in the body. B-lymphocytes (also called B cells) make antibodies to fight bacteria, and T-lymphocytes (also called T cells) kill viruses and foreign cells and trigger the B cells to make antibodies.
Groups of bean-shaped organs called lymph nodes are located throughout the body at different sites in the lymph system. Lymph nodes are found in clusters in the abdomen, groin, pelvis, underarms, and neck. Other parts of the lymph system include the spleen, which makes lymphocytes and filters blood; the thymus, an organ under the breastbone; and the tonsils, located in the throat.
Because lymph tissue is found in so many parts of the body, NHL can start almost anywhere and can spread to almost any organ in the body. It most often begins in the lymph nodes, liver, or spleen, but can also involve the stomach, intestines, skin, thyroid gland, brain, or any other part of the body.
There are different types and many subtypes of NHL. It is very important to know which type and subtype has been diagnosed. Specific information can be found in Subtypes of NHL.
In 2008, an estimated 66,120 people (35,450 men and 30,670 women) in the United States will be diagnosed with NHL. It is estimated that 19,160 deaths (9,790 men and 9,370 women) from this disease will occur this year.
Although NHL is a common childhood cancer, more than 90% of all cases occur in adults. NHL is the fifth most common cancer among both men and women. It is also the ninth most common cause of cancer death in men and sixth most common cause of cancer death among women.
The one-year relative survival rate (the percentage of patients who survive at least one year after the cancer is detected, excluding those who die from other diseases) of patients with NHL is 79%. The five-year and 10-year relative survival rates are 63% and 51%, respectively.
Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of the many different types of lymphoma in the United States and may not apply to a single person or type of lymphoma. It is not possible to tell a person how long he or she will live with NHL. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not reflect recent advances made in the treatment or diagnosis of this cancer.
Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2008.
There are different types and many subtypes of NHL, and it is very important to know which type and subtype has been diagnosed. Below are the most common types and subtypes, including information on how each may be treated. For more information on the treatment information described here, please read the Treatment section.
First, the disease is generally described by how quickly the cancer is growing: indolent or aggressive. Indolent grade and aggressive NHLs are about equally common in adults. In children, aggressive NHL is more common.
Indolent (low-grade) NHL. These types of lymphoma grow very slowly and tend to be advanced by the time they are diagnosed; around 85% to 90% of patients with indolent NHL have advanced disease when they first visit an oncologist (a doctor who specializes in cancer). This type of lymphoma usually responds well to several different types of treatment, but it may also recur (return after treatment). In some cases, patients with indolent NHL may also be able to be followed closely and start treatment only when necessary; this approach is called watchful waiting. In cases of localized disease (stage I-II), curative treatment with radiation therapy is possible.
Aggressive (high-grade) NHL. Theses types of lymphoma usually require chemotherapy that may be very intensive. These lymphomas are often curable.
Some subtypes of lymphoma cannot easily be classified as indolent or aggressive. For example, mantle cell lymphoma (see below) has features of both indolent and aggressive NHL.
Second, the doctor will determine what type of cell the lymphoma started in and classify the disease within two major groups:
B-cell lymphoma. B-cell lymphoma makes up about 90% of all cases of lymphoma.
T-cell lymphoma. T-cell lymphoma makes up about 10% of all lymphoma cases.
Subtyping
In addition to determining if the NHL is indolent or aggressive, and whether it is B-cell or T-cell, it is very important to determine the subtype of NHL because each subtype can behave differently and may require different treatments. There are about 35 recognized subtypes of NHL; the most common subtypes are described below. Distinguishing between the different subtypes of NHL can be difficult and requires specialized pathologists (doctors who specialize in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) who are experienced in the diagnosis of lymphoma. Such specialists will use sophisticated techniques and work closely with experienced oncologists. The diagnosis is based on how the lymphoma looks under the microscope and confirmed by additional information from other tests, including tests of genetic material within the lymphoma cells. For more information, see Diagnosis.
Subtypes of B-cell lymphoma
The most common subtypes of B-cell lymphoma follow.
Diffuse large B-cell lymphoma (DLBCL). This is the most common form of lymphoma (about 30% of all cases of NHL). This subtype is considered an aggressive form of NHL and involves organs outside the lymph nodes in about 40% of cases at the time of diagnosis. This type of lymphoma is often curable with treatment based on anthracycline (doxorubicin [Adriamycin, Rubex])-containing chemotherapy, possibly combined with radiation therapy or monoclonal antibodies. Treatments involving the central nervous system (CNS) may be included to prevent the lymphoma from spreading to the brain (called CNS prophylaxis). New genetic studies show that there may be different subtypes of DLBCL, called germinal center and non-germinal center.
Follicular lymphoma. This is the second most common form of lymphoma in the United States and Europe and accounts for about 20% of all cases of NHL. It usually begins in the lymph nodes, is most often indolent, and grows very slowly. There is no known cure; about 50% of people survive at least eight to 10 years after diagnosis. Patients with follicular lymphoma may be treated with combination chemotherapy, monoclonal antibodies, radiation therapy, or may be followed closely with watchful waiting. Over time, follicular lymphoma may transform into a diffuse large B-cell lymphoma (see above), which will then require more aggressive therapy. Stem cell transplantations, tumor vaccines, interferon, and monoclonal antibody treatments may also be available in clinical trials. Recent clinical trials have suggested that the survival for patients with follicular lymphoma has improved over the last few years, although this needs more research to confirm. Local radiation therapy may cure early-stage (stage I-II) disease.
Small lymphocytic lymphoma. This type of lymphoma is very closely related to a disease called B-cell chronic lymphocytic lymphoma (CLL) and represents about 5% of all NHL cases. It is considered an indolent lymphoma. Patients with small lymphocytic lymphoma may be treated with a combination of chemotherapy, monoclonal antibodies, radiation therapy, or may be followed closely with watchful waiting. Stem cell transplantations, tumor vaccines, interferon, and monoclonal antibody treatments may also be available in clinical trials.
Splenic marginal zone B-cell lymphoma. This type of lymphoma begins in the spleen and can also involve the blood. It is an uncommon form of B-cell CLL. It is usually slow-acting and often requires no treatment. Sometimes, surgical removal of the spleen is recommended.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). This type of lymphoma most commonly occurs in the stomach, but it may also occur in the lung, skin, thyroid, salivary gland, or eye. Patients with this type of lymphoma often have a history of autoimmune disease. When MALT occurs in the stomach, it is often successfully treated with antibiotics to treat a bacterium called Helicobacter pylori, which is thought to stimulate the lymphoma. In other cases, radiation treatment, surgery, chemotherapy, monoclonal antibodies, or a combination of these is the most common treatment.
Nodal marginal zone B-cell lymphoma. This type of indolent lymphoma involves the lymph nodes. It is rare, accounting for about 1% of all lymphomas. In general, this type of lymphoma is treated similarly to follicular lymphoma (see above).
Lymphoplasmacytic lymphoma. This is an indolent form of lymphoma that accounts for 1% of all NHL cases. This form of lymphoma most often involves the bone marrow, lymph nodes, and spleen. Patients with lymphoplasmacytic lymphoma often experience hyperviscosity (thickened blood) that may cause them to feel chills. Treatment is similar to chronic lymphocytic lymphoma/leukemia and may include a combination of chemotherapy, watchful waiting, interferon, or monoclonal antibodies. Chemotherapy followed by stem cell transplantation is being explored in clinical trials.
Mantle cell lymphoma. This is an aggressive subtype that makes up 7% of all NHL cases. It most often appears in people over age 60. It usually involves the bone marrow, lymph nodes, spleen, and gastrointestinal system and is identified by its expression of a protein called the cyclin D1 protein. Mantle cell lymphoma often does not respond, or stops responding, to chemotherapy. At this time, there is substantial debate about the best management for mantle cell lymphoma. A drug called bortezomib (Velcade) has been shown to be effective in this disease and is now being studied in clinical trials as part of the first-line chemotherapy. Clinical trials using high-dose chemotherapy followed by stem cell transplantation, interferon, or monoclonal antibodies after anthracycline-containing chemotherapy regimens are in progress. Several new drugs are also under investigation for mantle cell lymphoma.
Mediastinal large B-cell lymphoma. This is an aggressive form of diffuse large B-cell lymphoma (see above). It appears as a large mass in the chest area, which may cause respiratory symptoms or superior vena cava syndrome (SVCS), a collection of symptoms caused by the partial blockage or compression of the superior vena cava, the major vein that carries blood from the head, neck, upper chest, and arms to the heart. Mediastinal large B-cell lymphoma is most common in women between the ages of 30 and 40 and represents about 2.5% of all NHL cases. It is treated most often with anthracycline-based chemotherapy, and most patients also receive rituximab (Rituxan) and radiation therapy to the chest. Although radiation therapy has traditionally been considered a particularly important component for some patients in the treatment of mediastinal large B-cell lymphoma, this is no longer certain. Stem cell transplantation may be used when mediastinal large B-cell lymphoma does not respond well to chemotherapy.
Primary effusion lymphoma. This very aggressive form of lymphoma most often occurs in people who are HIV positive, otherwise immunocompromised, or elderly. It appears in the lung, heart, or abdominal cavities; often, there is not one identifiable tumor mass. It is treated the same as other diffuse large cell lymphoma (see above).
Burkitt lymphoma/Burkitt cell leukemia. This is a very rare and aggressive form of lymphoma. There are three forms of Burkitt lymphoma: endemic, sporadic, and immunodeficiency-related lymphoma. It occurs most commonly in Africa, appears most often in the jawbones of children, and is usually associated with the Epstein-Barr virus (EBV, the virus that causes infectious mononucleosis, also known as "mono"). In the United States, it appears most often in a child's abdomen. It is often curable with doxorubicin-based chemotherapy. Bone marrow transplantation for Burkitt lymphoma may be helpful.
Subtypes of T-cell lymphoma
The most common subtypes of T cell and natural killer (NK) lymphoma follow.
Precursor T-lymphoblastic lymphoma/leukemia (precursor T-cell acute lymphoblastic leukemia). This type of lymphoma makes up about 15% of all childhood cases of acute lymphocytic lymphoma (ALL) and about 25% of all adult cases of ALL. It is most common in late childhood, adolescence, and early adulthood, and is more common in males. It is called leukemia if there are more than 25% bone marrow blasts (immature white blood cells); it is called lymphoma if there are fewer than 25% bone marrow blasts and a mediastinal mass (a mass forming in the chest area) or there is a mass elsewhere. Lymphoblastic lymphoma most often begins as a large mass in the chest area that moves quickly to the bone marrow. This is considered a very aggressive form of lymphoma. It is treated with intensive chemotherapy, sometimes including bone marrow transplantation and may include radiation therapy.
Adult T-cell lymphoma/leukemia (human T-cell lymphotropic virus type I positive). This type of lymphoma is caused by a virus called the human T-cell lymphotropic virus type I. It is an aggressive disease that most often involves the bone and skin; often, lymphoma cells are found in the blood, which is why this condition is sometimes also called leukemia. This form of lymphoma usually does not respond well to chemotherapy, though some successes have been seen with ziduvidine (Retrovir) and interferon. About two-thirds of patients experience remission (temporary or permanent absence of symptoms).
Extranodal NK/T-cell lymphoma, nasal type. This is an aggressive type of lymphoma that is very rare in the United States and Europe but more common in Asian and Hispanic communities. It can occur in children or adults, most often involving the nasal area and sinuses. But, it can also involve the trachea, gastrointestinal tract, testicles (males), or skin. It often does not respond well to standard chemotherapy, but it may be treated with radiation therapy followed by chemotherapy. Bone marrow or peripheral stem cell transplantation for this type of lymphoma is being studied in clinical trials.
Enteropathy type T-cell lymphoma. This type of lymphoma is rare in the United States and Europe. This is an aggressive form of T-cell lymphoma that involves the intestines of patients who have celiac disease (gluten intolerance). If left untreated, it can damage the intestines severely. This type of lymphoma may be preventable if people who know they have celiac disease adopt a gluten-free diet. High-dose chemotherapy may be used to treat enteropathy type T-cell lymphoma.
Gamma/delta hepatosplenic T-cell lymphoma. This is an aggressive form of peripheral T-cell lymphoma that involves the liver and spleen. It occurs most often in male adolescents and young men. It is treated as a high-risk diffuse large cell lymphoma (see above).
Subcutaneous panniculitis-like T-cell lymphoma. This is a form of peripheral T-cell lymphoma that is similar to gamma/delta hepatosplenic T-cell lymphoma. It involves the tissues under the skin and is often first diagnosed as panniculitis (inflammation of fatty tissues). It is treated as a high-risk aggressive lymphoma.
Anaplastic large cell lymphoma, T/null-cell, primary cutaneous lymphoma. This lymphoma involves the skin only. It is often indolent, although aggressive subtypes of the disease are possible. When localized, radiation therapy is often effective. If there is spread, doxorubicin-based chemotherapy is the usual management.
Peripheral T-cell lymphoma. This is an aggressive form of lymphoma that is most often discovered at an advanced stage. It is most common in people over 60 and makes up about 6% of all lymphoma in the United States and Europe. The cells of this lymphoma are variable in size and they express certain types of proteins (CD4 or CD8) on their surface. It is treated like diffuse large B-cell lymphoma (see above), with doxorubicin-based chemotherapy. Stem cell transplantation may be considered in some cases.
Angioimmunoblastic T-cell lymphoma. This is an aggressive form of lymphoma marked by the symptoms it produces: swollen lymph nodes, fever, weight loss, rash, and high levels of antibodies called gamma globulin in the blood. Since patients with angioimmunoblastic lymphoma have depressed immune systems, infections are also common. This type of lymphoma is identified by specific genetic changes found on the T-cell receptors. It is managed like other diffuse large cell lymphomas.
Anaplastic large cell lymphoma, T/null-cell, primary systemic type. This form makes up about 2% of all lymphoma and about 10% of all childhood lymphoma. An increased amount of the ALK-1 protein in the cancer cells is characteristic of this subtype of lymphoma. It occurs in both adults and children. It is an aggressive form of lymphoma that often responds well to treatment.
More information on the specific treatment options described above can be found under the Treatment section. Cancer survival statistics should be interpreted with caution because it is not possible to tell an individual how long he or she will live with NHL.
A risk factor is anything that increases a person's chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.
The exact cause of NHL is not known. The following factors can raise a person's risk of developing NHL:
Age. The risk of NHL increases with age. The most common types occur most commonly in people in their 60s and 70s.
Gender. Men are more likely to develop NHL than women.
Infections. Some types of NHL are associated with specific infections. For example, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, also called MALT lymphoma, is thought to be caused by a bacterium known as Helicobacter pylori. If this lymphoma is diagnosed very early, the lymphoma will sometimes go away if the bacterium is eliminated from the stomach with antibiotics. Other types of MALT lymphoma, including those affecting the lungs and the tear glands, may also be caused by infections.
Virus exposure. Viruses are thought to be involved in causing some types of NHL. For example, EBV is associated with some types of NHL, including Burkitt lymphoma, and lymphomas occurring after solid organ transplantations. However, the virus is probably not the only factor, so people who have had mono do not necessarily have an increased risk of developing NHL in the future. Other viruses have also been identified as being important in causing other rare types of lymphoma.
Immune deficiency disorders. Immune system disorders, such as human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (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, are at an increased risk for developing certain types of NHL. Also, some drugs used to treat autoimmune disorders may increase the risk of NHL.
Organ transplantation. Organ transplant recipients are at a higher risk for NHL because of the immune-suppressing drugs that must be taken.
Previous cancer treatment. Previous treatment with certain drugs for other types of cancer may increase the risk of NHL.
Chemical exposure. Exposure to certain chemicals, such as pesticides and petrochemicals, may increase the risk of NHL.
People with NHL may experience the following symptoms. Sometimes, people with NHL do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your doctor.
The symptoms of NHL depend on where the cancer starts and the organ that is involved.
General symptoms:
Swelling or lumps in the lymph nodes in the abdomen, groin, neck, or underarm
Fever that cannot be explained by an infection or other illness
Weight loss with no known cause
Sweating and chills
Examples of symptoms related to tumor location:
Tumors in the abdomen can cause a distended (stretched) belly or pain.
A tumor in the center of the chest pressing on the windpipe can cause difficulty breathing or other respiratory problems.
The doctor may use certain symptoms to help describe the disease, called Staging. Each stage may be subdivided into "A" and "B" categories.
A means that an individual did not experience B symptoms listed below.
B means that an individual experienced the following symptoms:
Unexplained weight loss of more than 10% of original body weight during the six months before diagnosis
Unexplained fever with temperatures above 38º C (100.4º F)
Drenching night sweats. Most patients report that either their nightclothes or the sheets on the bed are actually wet. Sometimes, heavy sweating occurs during the day.
Doctors use many tests to diagnose cancer and determine if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the lymphoma has metastasized. Your doctor may consider these factors when choosing a diagnostic test:
Age and medical condition
The type of lymphoma
Severity of symptoms
Previous test results
To determine if a person has NHL, the doctor will first take a complete medical history and do a physical examination, paying special attention to the lymph nodes, liver, and spleen. The doctor will also look for signs of infection that may cause the lymph nodes to swell and may prescribe antibiotics; if the swelling in the lymph nodes still does not go down after antibiotics, the swelling may be caused by something other than an infection. If the doctor suspects lymphoma, he or she may order a biopsy, as well as laboratory and imaging tests.
The following tests may be used to diagnose NHL:
Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. To diagnose lymphoma, the most common type is a biopsy from lymph nodes in the neck, under the arms, or in the groin. A biopsy may also be taken from the chest or abdomen during a computed tomography (CT) scan, or from the stomach or intestine during an endoscopy (a diagnostic examination that allows a doctor to examine the inside of the body). A biopsy is the only way to make a definite diagnosis of lymphoma and to determine the subtype. The tissue sample should be analyzed by a pathologist experienced in the diagnosis of lymphoma; second opinions may also be helpful.
Since many subtypes of lymphoma are identified by specific genetic changes or molecular activity, cytogenetics (the study of genetic changes in cells) and molecular studies may be performed on the biopsy sample. For example, the tumor cells in the NHL subtype of mantle cell lymphoma contain a translocation of chromosomes 11 and 14, which means that parts of these two chromosomes have traded places. Other types of lymphoma are identified by abnormal amounts of certain proteins.
Bone marrow aspiration and biopsy. Lymphoma often spreads to the bone marrow, the spongy material in the center of bones where blood cells are produced. Looking at a sample of the bone marrow can be important for doctors in the diagnosis of lymphoma and to determine if the lymphoma has spread.
The most common site to biopsy the bone marrow is the back of the pelvic (hip) bone. The skin is numbed, and a needle is inserted into a bone in the hip until it reaches the marrow. A small amount of bone marrow is removed and examined under a microscope.
Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. A contrast medium (special dye) is injected into a patient's vein to provide better detail and locate the exact position of a tumor. CT scans of the chest and abdomen can help find cancer that has spread to the lungs, lymph nodes, and liver.
Magnetic resonance imaging (MRI) scan. This test uses magnetic fields, not x-rays, to view the inside of the body, including the brain and spinal column. MRIs create better images of certain tissues than CT scans and do not involve radiation.
Bone scans. Bone scans can show if cancer has spread to the skeletal system. In this procedure, the doctor injects a small amount of radioactive material into the patient's vein. The substance collects in the bone, gives off gamma radiation, and can be detected by a special camera. Healthy bone cells appear gray to the camera, and areas that have cancer cells appear dark.
Positron emission tomography (PET) scan. A PET scan is a test that creates an image of the body using an injection of a substance, such as glucose (sugar), in a low-dose, radioactive form to determine the metabolic activity in cells. It can show the difference between benign shadows and true malignancies (cancer) that may show up on a CT scan or MRI. The exact accuracy and role of PET scanning in NHL is not yet clear, although aggressive lymphomas often show up on PET scans. Many oncologists will obtain a PET scan as part of the initial evaluation, especially for the aggressive lymphomas. In the future, a PET scan may help monitor the disease's response to treatment. There is also some evidence that using a PET scan after one or two cycles of treatment may be a useful way of predicting whether that treatment is likely to completely eliminate the lymphoma. This is not yet proven, but it is being evaluated in many studies around the world.
Staging is a way of describing cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the lymphoma's stage, so staging may not be complete until all 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 (chance of recovery). There are different stage descriptions for different types of cancer.
When staging NHL, doctors evaluate the following:
The number of cancerous lymph node areas
The location of the cancerous lymph nodes: regional (in the same area the cancer began) or distant (in other parts of the body)
If the cancerous lymph nodes are on one or both sides of the diaphragm (the thin muscle under the lungs and heart that separates the chest from the abdomen)
If the disease has spread to the bone marrow, spleen, or extralymphatic organs (organs outside the lymphatic system) such as the liver, lungs, or brain
The stage of lymphoma describes the extent of spread of the tumor, using Roman numerals one through four (I, II, III, or IV).
Stage I: Either one of these conditions:
The cancer is found in one lymph node region (stage I).
The cancer has invaded one extralymphatic organ or site (identified using the letter "E") but not any lymph node regions (stage IE).
Stage II: Either one of these conditions:
The cancer is in two or more lymph node regions on the same side of the diaphragm (stage II).
The cancer involves a single organ and its regional lymph nodes, with or without cancer in other lymph node regions on the same side of the diaphragm (stage IIE).
Stage III:
There is cancer in lymph node areas on both sides of the diaphragm (stage III).
There may also be involvement of an extralymphatic organ (stage IIIE), the spleen using the letter "S" (stage IIIS), or both (stage IIIES).
Stage IV: Lymphoma is called stage IV if there is disseminated involvement of organs beyond the lymph nodes. Common sites for spread are the liver, bone marrow, or lungs.
Progressive or recurrent: Progressive disease is present if the cancer becomes larger or spreads while the patient is being treated for the original lymphoma. Recurrent lymphoma means the lymphoma 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.
International Prognostic Index. In addition to stage, a scale called the International Prognostic Index (IPI) is important in planning treatment. The IPI was developed based on evidence from thousands of patients with lymphoma. The results indicated that certain features could help predict how successful treatment will be, with individuals classified into low-risk or high-risk groups. As explained in Symptoms, each stage may also be subdivided into "A" and "B" categories, based on the presence or absence of specific symptoms.
Features that the IPI identifies as risk factors:
Age 60 or older
Stage III or stage IV disease
Blood test results showing higher than normal levels of LDH (a group of enzymes called lactate dehydrogenase)
Lower overall health or performance status
Presence of cancer in multiple extranodal sites (organs or sites outside the lymph node region)
For patients with follicular lymphoma, additional features, such as the level of a patient's hemoglobin and the number of lymph node groups involved, are also used.
These factors are used to estimate the chances of cure. For noncurable lymphoma, they help to predict how aggressive the lymphoma will be for an individual patient. This index is now used widely to help doctors make decisions about treatment.
Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer-Verlag New York, www.springer-ny.com.
The treatment of NHL depends on the stage of the cancer, whether the cancer has spread, and the person's overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.
There are three main treatments for NHL: chemotherapy, radiation therapy, and biologic therapy. Occasionally, surgery may play a role. Since knowledge of genetic and chromosomal makeup of all cancers, including lymphoma, is developing rapidly, clinical trials (research studies that evaluate new methods of treatment) may also be recommended for many patients.
Watchful waiting
Some patients with indolent lymphoma may not require any immediate treatment if they are otherwise well and the lymphoma is not causing any symptoms or problems with other organs. In these cases, patients are closely monitored, and treatment only begins if symptoms or tests indicate that the cancer is progressing. This is referred to as watchful waiting (also called watch-and-wait and active surveillance). There is very good evidence that, in some patients with indolent lymphoma, the watch-and-wait approach does not affect the chances of survival as long as regular and careful follow-up is performed.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. It is the primary treatment for NHL. Chemotherapy may be given by mouth or injected into a vein.
The chemotherapy used depends on the stage and type of the cancer. The most common chemotherapy combination for the initial treatment of NHL is called CHOP and contains four drugs: cyclophosphamide (Cytoxan, Neosar), doxorubicin (Adriamycin, Rubex), vincristine (Oncovin), and prednisone (a type of corticosteroid). Recent evidence has shown that for patients with B-cell lymphoma, the addition of a monoclonal antibody known as rituximab (Rituxan) (see the section on monoclonal antibodies below) to CHOP gives better results than the use of CHOP alone.
Chemotherapy attacks rapidly dividing cells, including those in normal tissues such as the hair follicles, lining of the mouth, intestines, and bone marrow. Side effects depend on the type of drug used, the dosage used, and how long it is taken. Chemotherapy may cause people to lose their hair, develop mouth sores, or have nausea and vomiting. Chemotherapy may lower the body's resistance to infection, cause fatigue, and lead to increased bruising and bleeding. Other side effects may include numbness and tingling in the fingers and toes, loss of appetite, constipation, or diarrhea.
Most side effects, including risk of infection, can be controlled during treatment and go away after chemotherapy is completed. Chemotherapy may also cause long-term side effects, also called late effects.
The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.
Radiation therapy
Radiation therapy is the use of high energy x-rays or other particles are used to kill cancer cells and shrink malignant tumors. Radiation for NHL is usually external-beam radiation therapy, which uses a machine to deliver radiation to the site of the body where the cancer is located. For patients with lymphoma, it is mainly used with those who have a tumor in the early-stage disease or have lymph node that is particularly large (usually more than 10 cm). Radiation therapy is usually given following or in addition to chemotherapy. It is often given to patients who have mediastinal B-cell lymphoma.
Since radiation therapy kills healthy cells as well as cancer cells, patients may experience immediate side effects depending on the area of the body treated. These may include mild skin irritations, upset stomach, loose bowel movements, nausea, and sore throat. Most patients feel tired. Many side effects can be helped by medication and usually go away when treatment is finished. Radiation therapy may also cause late effects.
Biologic therapy
Also called immunotherapy, biologic therapy uses the body's immune system to fight cancer. Monoclonal antibodies, interferon, and vaccines are biologic therapies being tested in clinical trials as treatments for NHL.
Monoclonal antibodies. The monoclonal antibody, rituximab, is used to treat many different types of B-cell lymphoma. Rituximab works by targeting a cell-surface molecule called CD20. When the antibody attaches to this antigen, some lymphoma cells die and others appear to become more susceptible to chemotherapy. Although it is quite effective by itself, there is increasing evidence that, when added to chemotherapy for patients with most types of B-cell NHL, it produces better results than chemotherapy alone.
Radiolabeled antibodies. Radiolabeled antibodies are monoclonal antibodies with tethered radioactive particles that are designed to focus radioactivity directly on the lymphoma cells. This type of drug (ibritumomab tiuxetan [Zevalin] and tositumomab and iodine I-131 [Bexxar] are the two drugs currently available) is relatively new and much is still being learned. In general, the radioactive antibodies are thought to be stronger than regular monoclonal antibodies but harder on the bone marrow. This type of therapy is referred to as radioimmunotherapy (RIT).
Interferon. Interferons are proteins that help strengthen the immune system and are given alone or together with chemotherapy for some types of low-grade lymphoma.
Stem cell transplantation is a technique used to treat NHL with very high doses of chemotherapy to kill cancer cells and introducing new stem cells (that can form new blood cells) into the body. It is a difficult treatment and is generally reserved for patients with NHL whose disease is progressive or recurrent.
Stem cells are blood-forming cells found in the bone marrow. They can be collected and used for transplantation, either from the bone marrow in the hipbone or, more commonly, from the blood. If the stem cells come from the patient, it is called an autologous (AUTO) transplantation. If the marrow comes from another person, it is called an allogeneic (ALLO) transplantation.
In an AUTO transplant, stem cells from the bone marrow are "mobilized" into the blood by treating the patient with chemotherapy and another drug known as G-CSF (granulocyte colony stimulating factor). The stem cells are then collected from the blood, frozen, and stored. In an ALLO transplant, the donor stem cells are collected from the donor on or near the actual transplant day; the patient receives these fresh and unfrozen. After this (in both AUTO or ALLO transplants), the patient receives very high doses of chemotherapy (sometimes also with radiation therapy) to treat the NHL. These high doses are used since patients who undergo this treatment have disease that has proven to be resistant to normal chemotherapy doses. Higher doses of chemotherapy are more effective against recurrent NHL than standard doses of chemotherapy.
Although the patient's bone marrow may have been severely damaged by this high-dose chemotherapy treatment, the stem cells will be given back to the patient by means of an intravenous (IV) infusion and will restore blood cell production.
A mini (non-ablative)-allogeneic transplantation is one that uses reduced intensity treatments before the transplantation. It is sometimes given to patients who may not have the strength to go through the standard bone marrow transplantation process and is being evaluated in clinical trials to determine if it is effective in treating lymphoma.
If NHL recurs (comes back) after treatment is finished, it is called recurrent or relapsed NHL. If NHL is still present after initial treatment, the disease is called refractory NHL. Choice of treatment for recurrent NHL depends on three factors: where the cancer comes back, the type of treatment given previously, and the patient's overall health. The doctor may use chemotherapy or bone marrow transplantation or may recommend a clinical trial.
The National Comprehensive Cancer Network (NCCN) has a series of treatment guidelines that have been translated into patient-friendly language. In accordance with Cancer.Net's Linking Policy, please note that this link does not imply ASCO's endorsement of the content, but rather it is an effort to provide additional information that may be helpful to people living with cancer and their families. The NCCN treatment guide for NHL can be found at www.nccn.org.
Doctors and scientists are always looking for better ways to treat patients with NHL. A clinical trial is a way to test a new treatment in order to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy drugs, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.
Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that finding new drugs and other therapies is the only way to make progress in treating NHL. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with NHL.
To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient's options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.
Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below are some of the side effects that are more common to NHL and its treatments. For more detailed information on managing these and other side effects of cancer and cancer treatment, visit the Cancer.Net Managing Side Effects section.
Diarrhea. Diarrhea means frequent, loose, or watery bowel movements. It is a common side effect of certain chemotherapy or radiation therapy to the pelvis, such as in women with uterine, cervical, or ovarian cancers. It can also be caused by certain tumors, such as pancreatic cancer.
Dry mouth (xerostomia). Xerostomia occurs when the salivary glands do not make enough saliva (spit) to keep the mouth moist. Because saliva is needed for chewing, swallowing, tasting, and talking, these activities may be more difficult with a dry mouth. Dry mouth can be caused by chemotherapy or radiation treatment, which can damage the salivary glands. Dry mouth caused by chemotherapy is usually temporary and normally clears up about two to eight weeks after treatment ends. Radiation treatment to the head, face, or neck can cause dry mouth and is most common with radiation treatment to the oral cavity to treat head and neck cancer. It can take six months or longer for the salivary glands to start producing saliva again after the end of treatment.
Fatigue (tiredness). Fatigue is extreme exhaustion or tiredness and is the most common problem patients with cancer experience. More than half of patients experience fatigue during chemotherapy or radiation therapy, and up to 70% of patients with advanced cancer experience fatigue. Patients who feel fatigue often say that even a small effort, such as walking across a room, can seem like too much. Fatigue can seriously affect family and other daily activities, can make patients avoid or skip cancer treatments, and may even affect the will to live.
Hair loss (alopecia). A potential side effect of radiation therapy and chemotherapy is hair loss. Radiation therapy and chemotherapy cause hair loss by damaging the hair follicles responsible for hair growth. With chemotherapy, hair loss may occur throughout the body, including the head, face, arms, legs, underarms, and pubic area. The hair may fall out entirely, gradually, or in sections. In some cases, the hair will simply thin-sometimes unnoticeably-and may become duller and dryer. With radiation therapy, hair loss is restricted to the area being treated. Losing one's hair can be a psychologically and emotionally challenging experience and can affect a patient's self-image and quality of life. However, the hair loss is usually temporary, and the hair often grows back.
Hypercalcemia. Hypercalcemia is an uncommon but serious complication of lymphoma treatment. It implies unusually high level of calcium in the blood. Hypercalcemia can be life threatening and is the most common metabolic disorder associated with cancer, occurring in 10% to 20% of patients with cancer. While most of the calcium in the body is stored in the bones, about 1% of the body's calcium circulates in the bloodstream. Calcium is important for many bodily functions, including bone formation, muscle contractions, and nerve and brain function. Patients with hypercalcemia may experience loss of appetite, nausea and/or vomiting; constipation and abdominal pain; increased thirst and frequent urination; fatigue, weakness, and muscle pain; changes in mental status, including confusion, disorientation, and difficulty thinking; and headaches. Severe hypercalcemia can be associated with kidney stones, irregular heartbeat or heart attack, and eventually loss of consciousness and coma.
Infection. An infection occurs when harmful bacteria, viruses, or fungi (such as yeast) invade the body and the immune system is not able to destroy them quickly enough. Patients with cancer are more likely to develop infections because both cancer and cancer treatments (particularly chemotherapy and radiation therapy to the bone marrow or extensive areas of the body) can weaken the immune system. Symptoms of infection include fever (temperature of 100.5°F or higher); chills or sweating; sore throat or sores in the mouth; abdominal pain; pain or burning when urinating or frequent urination; diarrhea or sores around the anus; cough or breathlessness; redness, swelling, or pain, particularly around a cut or wound; and unusual vaginal discharge or itching.
Mouth sores (mucositis). Mucositis is an inflammation of the inside of the mouth and throat, leading to painful ulcers and mouth sores. It occurs in up to 40% of patients receiving chemotherapy treatments. Mucositis can be caused by chemotherapy directly, the reduced immunity brought on by chemotherapy, or radiation treatment to the head and neck area.
Nausea and vomiting. Vomiting, also called emesis or throwing up, is the act of expelling the contents of the stomach through the mouth. It is a natural way for the body to rid itself of harmful substances. Nausea is the urge to vomit. Nausea and vomiting are common in patients receiving chemotherapy for cancer and in some patients receiving radiation therapy. Many patients with cancer say they fear nausea and vomiting more than any other side effects of treatment. When it is minor and treated quickly, nausea and vomiting can be quite uncomfortable but cause no serious problems. Persistent vomiting can cause dehydration, electrolyte imbalance, weight loss, depression, and avoidance of chemotherapy. There are very effective drugs for the treatment of nausea and vomiting.
Superior vena cava syndrome (SVCS). SVCS is a collection of symptoms caused by the partial blockage or compression of the superior vena cava, the major vein that carries blood from the head, neck, upper chest, and arms to the heart. Nearly 95% of SVCS cases are caused by cancer. The most likely cancers to cause SVCS are lung cancer (especially small cell lung cancer), squamous cell lung cancer, adenocarcinoma of the lung, NHL, large cell lung cancer, and other cancers that spread to the chest. The superior vena cava, which drains into the right atrium of the heart, can become compressed when a tumor growing inside the chest presses on the vein. Because the superior vena cava lies close to a number of lymph nodes, any cancer that spreads to these lymph nodes, causing them to enlarge, can also cause SVCS. Enlarged lymph nodes compress the vein, which slows the blood flow and may ultimately result in complete blockage.
Thrombocytopenia. Thrombocytopenia is an unusually low level of platelets in the blood. Platelets, also called thrombocytes, are the blood cells that stop bleeding by plugging damaged blood vessels and helping the blood to clot. Patients with low levels of platelets bleed more easily and are prone to bruising. Platelets and red and white blood cells are made in the bone marrow, a spongy, fatty tissue found on the inside of larger bones. Certain types of chemotherapeutic drugs can damage the bone marrow so that it does not make enough platelets. Thrombocytopenia caused by chemotherapy is usually temporary. Other medications used to treat cancer may also lower the number of platelets. In addition, a patient's body can make antibodies to the platelets, which lowers the number of platelets.
After treatment for NHL ends, patients should continue to see their doctor on a regular basis for physical examinations, blood tests, and possibly scans or other imaging studies. This is called a follow-up care plan, and it is necessary to monitor your recovery for the coming months and years. For the first two years, visits to the doctor are usually every two or three months. If there is no evidence of disease, patients will not have to see the doctor as often, but should still return at least once a year for a checkup. Normally, follow-up visits are most frequent in the first three years after treatment. Follow-up visits should continue throughout the person's lifetime.
Patients who have undergone treatment for lymphoma have an increased risk of developing other diseases or conditions later in life, as the toxicity of chemotherapy or radiation treatment can cause permanent damage. Treatments have already improved in the last 30 years, and now patients who have been through treatment for lymphoma are less likely to experience late effects, but there is still some risk. Therefore, it is important that people stay current with their follow-up care to monitor any developments.
People who have received radiation therapy to the pelvis and high doses of cyclophosphamide are at risk for infertility (inability to have children).
All survivors of lymphoma are at higher risk for up to 20 years than the general population to develop a second cancer. The most common secondary cancers include cancer of the lung, brain, kidney, bladder, or melanoma, Hodgkin lymphoma, or leukemia.
Women who received radiation therapy to the chest are at increased risk for breast cancer.
Patients who receive doxorubicin-based chemotherapy or radiation treatment to the chest may be at higher risk for developing heart problems.
Adults who receive certain types of chemotherapy (alkylating agents and methotrexate [MTX, Amethopterin]) or radiation treatment to the chest area may be at risk for lung damage and shortness of breath later in life.
Patients who receive radiation treatment to the neck are at increased risk for thyroid deficiency later in life.
Patients who receive bone marrow transplantation or peripheral blood stem cell support may be at higher risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
Children who receive radiation treatment and chemotherapy to the brain and spinal cord area may be at risk for growth problems, learning disabilities, and delayed puberty. Teenagers who receive chemotherapy may be at higher risk for low sperm counts or damage to the ovaries.
Children who receive total body irradiation (TBI) as part of the bone marrow transplantation process may experience thyroid problems.
People recovering from NHL are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about Healthy Living After Cancer.
Research for NHL is ongoing. The following are examples of questions recently under investigation in clinical trials but may not be approved or available at this time. Always discuss all diagnostic and treatment options with your doctor.
Vaccines. Several vaccines are now being assessed in clinical trials, mostly for low-grade lymphoma. They are not intended to prevent lymphoma but to reduce the chance that a lymphoma will recur after treatment. In this type of vaccine treatment, doctors take a sample of an affected lymph node and use it to develop a vaccine. The lymphoma is then treated with chemotherapy. After the end of treatment, a series of injections of the vaccine are given, which may boost the body's immunity against tumor cells. These vaccines may one day prove to prevent or delay the recurrence of lymphoma.
Gene profiling. As scientists learn more about the genetics and the specific role that gene mutations play in cancer formation, they are better able to classify and diagnose subtypes of NHL. Then, therapies can be designed that work against specific genetic changes and counteract their effects.
Immunotherapy. Many new antibodies are being developed that boost the body's natural defenses against cancer. Some use antibodies that attach to the surface of tumor cells. Some have radioactive substances attached to "target" radiation treatment on the lymphoma. This form of treatment is known as radioimmunotherapy.
Targeted therapies. There are many new targeted treatments for lymphoma in early clinical trials and under evaluation in the laboratory. Targeted therapies are drugs that have been developed against specific genes or proteins within the lymphoma cells that are thought to be important in the development of cancer. It is hoped that because these drugs are directed against very specific targets that found only in lymphoma cells, they will have fewer side effects than chemotherapy or radiation therapy.
Other advances. Different combinations of chemotherapy agents and different chemotherapy schedules (sometimes with antibodies or radiolabeled antibodies) are being investigated in clinical trials. Also, many new drugs, which work differently from standard chemotherapy drugs are now being evaluated in clinical trials. The use of different types of stem cell transplantation, including allogeneic or mini-allogeneic transplants, is also being tested in patients with newly diagnosed disease, and in those who have had a relapse after the first-line treatment. For many types of lymphoma, the best way to use stem cell transplants is still uncertain, which is why clinical trials of this approach are in progress.
Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:
Which type of lymphoma do I have?
Did a pathologist experienced in the diagnosis of lymphoma review the biopsy?
How many patients do you see with this type of lymphoma each year?
Where in my body has the disease spread?
What stage is it in? What does this mean?
What are the treatment options? What is the goal of each treatment?
Will I need surgery?
Will I need radiation therapy?
Will I need chemotherapy?
What is immunotherapy? Is this treatment appropriate for me?
What clinical trials are open to me?
Why is it sometimes appropriate to "watch and wait?"
What are the possible short-term and long-term side effects of each treatment?
Will this affect my ability to have children?
Is my lymphoma curable? If so, what are the chances for a cure?
Should I get a second opinion? Will this include a specialized pathologist reviewing the biopsy?
What caused my lymphoma?
How can I stay as healthy as possible during and after treatment?
After treatment ends, what is my follow-up care plan?
The Leukemia & Lymphoma Society
1311 Mamaroneck Ave., Ste. 130
White Plains, NY 10605
Toll Free: 800-955-4572 www.lls.org
Lymphoma Research Foundation
8800 Venice Blvd., Ste. 207
Los Angeles, CA 90034
Phone: 310-204-7040
Toll Free: 800-500-9976 www.lymphoma.org
American Society for Blood and Marrow Transplantation
85 W Algonquin Rd., Ste. 550
Arlington Heights, IL 60005
Phone: 847-427-0224 www.asbmt.org
Blood and Marrow Transplant Information Network
2900 Skokie Valley Rd., Ste. 104
Highland Park, IL 60035
Phone: 847-433-3313
Toll Free: 888-597-7674 www.bmtnews.org
National Bone Marrow Transplant Link
20411 West 12 Mile Rd., Ste. 108
Southfield, MI 48076
Phone: 248-358-1886
Toll Free: 800-LINK-BMT (800-546-5268) www.nbmtlink.org
National Marrow Donor Program
3001 Broadway St., NE, Ste. 500
Minneapolis, MN 55413-1753
Phone: 800-MARROW2 (800-627-7692)
Pat. Adv.: 888-999-6743 www.marrow.org
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