Non Hodgkin’s Lymphoma

Non Hodgkin's Lymphoma

Also called: NHL

Reviewed By:
Mark Oren, M.D., FACP

Summary

Non-Hodgkin’s lymphoma (NHL) is the name given to a group of lymphomas, or cancers of the lymphoid tissue. Lymphoid tissue is part of the lymphatic system. A major component of the immune system, the lymphatic system consists of organs, lymph nodes and lymph vessels. This system manufactures and transports lymph (fluid made of plasma and white blood cells) from tissues to the bloodstream.

Lymphomas generally develop in the lymph nodes (small, bean-shaped organs located in groups in various areas of the body), or in some situations, in patches of lymphatic tissue in organs such as the stomach or intestines.

The term “non-Hodgkin’s lymphoma” is used to distinguish this group of lymphomas from the other main form of lymphoma, called Hodgkin’s lymphoma or Hodgkin’s disease. NHL is far more common than Hodgkin’s lymphoma, and can usually be distinguished from Hodgkin’s lymphoma when the cells are examined under a microscope. All types of lymphoma that are not diagnosed as Hodgkin’s lymphoma are considered non-Hodgkin’s lymphoma.

Although NHL has been linked to a number of risk factors, most people with the disease have no known risk factors, and the cause of their cancer is unknown. However, researchers have identified genetic defects that can cause normal cells to become lymphoma cells. These mutations may occur from exposure to radiation or cancer-causing chemicals, but many times the mutations occur for no apparent reason. In addition, deficiencies of the immune system appear to play a role in some cases of lymphoma. 

After a diagnosis has been confirmed, the patient typically is seen by an oncologist (a physician who specializes in the treatment of cancer) to stage the cancer. Staging is the process of determining how far the cancer has spread and is necessary for physicians to plan treatment. The main treatment methods for non-Hodgkin’s lymphoma include chemotherapy, radiation therapy and biological therapy.

There are no established prevention methods for non-Hodgkin’s lymphoma. Currently, the best way to prevent developing the disease is to avoid known risk factors, such as human immunodeficiency virus (HIV).

NHL is the fifth most common cancer in women and men in the United States, not counting non-melanoma skin cancers.  The American Cancer Society estimates in 2007 there will be more than 63,000 new cases of NHL. The incidence rates of NHL have nearly doubled in the past 35 years,. Thi increase is partially attributed to AIDS-related lymphomas. In 2007, the disease is expected to cause nearly 19,000 deaths. The overall 5-year survival rate for a patient with NHL is 63 percent. However, survival varies greatly by the cell type and stage of the cancer.

About non-Hodgkin’s lymphoma (NHL)

Non-Hodgkin’s lymphoma (NHL) is a type of lymphoma, or cancer of the lymphoid tissue. Lymphoid tissue is part of the lymph system. A major component of the immune system, the lymph system consists of organs, lymph nodes, and lymph vessels. The lymphatic system manufactures and transports lymph, which is composed of plasma (the fluid part of the blood),red blood cells and white blood cells from tissues to the bloodstream.

Although non-Hodgkin’s lymphoma can start anywhere, it generally develops in the lymph nodes. In some cases, the disease can develop in patches of lymphatic tissue in organs such as the spleen, stomach or intestines. Lymph nodes are small, bean-shaped organs located in groups in various areas of the body, including the neck, armpit, chest and groin. They are connected by lymph vessels which carry the lymph fluid.

The function of the lymph nodes includes producing immune cells (e.g., lymphocytes and plasma cells), and filtering bacteria, cancer cells and other foreign material from lymph. When the lymph nodes recognize bacteria in the lymph fluid, they respond by enlarging and producing additional white blood cells, including lymphocytes, to help combat infection.

In patients with lymphoma, lymphocytes begin to grow abnormally. The two types of lymphocytes are:

  • B lymphocytes (B-cells). B-cells defend the body from bacteria and other invading threats by changing into plasma cells, which produce antibodies. The antibodies then mark the antigens or these threats for destruction.

  • T lymphocytes (T-cells). T-cells destroy germs,  infected cells and cancer cells directly.

As the cells continue to grow and expand, the lymph glands or other organs in which the lymphocytes grow begin to enlarge. The cells form lumps in the body. Organ function may also become affected, as the lymphocyte masses grow larger, making it more difficult for normal cells to function.

The other main form of lymphoma is Hodgkin’s lymphoma, or Hodgkin’s disease. NHL is far more common than Hodgkin’s lymphoma, and can usually be distinguished from Hodgkin’s lymphoma by examining cells under a microscope.

NHL is the fifth most common cancer in women and men in the United States, not counting nonmelanoma skin cancers, according to the American Cancer Society (ACS). In 2007, the ACS estimates that more than 63,000 new cases of NHL will be diagnosed in the United States. It is slightly more common in men than in women, with about 34,000 new cases diagnosed in men each year and just over 29,000 new cases diagnosed in women. It is estimated that more than 330,000 Americans are currently living with NHL.

According to the ACS, a man’s risk of developing NHL in his lifetime is 1 in 46, while a woman has a 1 in 55 chance of getting NHL. Although some types of NHL are among the most common forms of cancer in children, more than 95 percent of NHL cases occur in adults, with the average age at diagnosis in the 60s. The disease is also more likely to develop in whites than in African Americans or Asian Americans.

Types and differences of NHL

Many classification systems have been developed for lymphomas, and experts disagree on exactly how they should be organized. The most recent classification system was developed by the World Health Organization (WHO). Whereas previous classification systems mainly relied on the appearance of the lymphoma cells, the WHO system relies on the genetic and chemical characteristics of the cells as well.

Types of non-Hodgkin’s lymphoma are first divided by cell type into B-cell or T-cell groups. They are then further classified by whether the tumors were derived from precursor (immature) or peripheral (mature) cells.

Non-Hodgkin’s lymphoma is generally classified as:

  • B-cell neoplasms
    • Precursor B-cell neoplasm
    • Peripheral B-cell neoplasms
      • Includes B-cell chronic lymphocytic leukemia/small lymphocytic leukemia, mantle cell lymphoma, hairy cell leukemia and Burkitt’s lymphoma
  • T-cell and putative natural killer cell (NK-cell) neoplasms
    • Precursor T-cell neoplasm
    • Peripheral T-cell and NK-cell neoplasms
      • Includes T-cell chronic lympocytic leukemia/prolymphoctic leukemia, T-cell granular lympocytic leukemia and peripheral T-cell lymphoma

Though there are many types of NHL, two forms are the most common. These include:

  • Diffuse large cell B-cell lymphoma (DLBCL). DLBCL accounts for approximately three out of 10 cases of lymphoma. Occurring mostly in older people, this cancer often grows rapidly.
  • Follicular lymphoma. Occurring mostly in adults, this form accounts for approximately two out of 10 cases of lymphoma. It is a slow-growing cancer in which the cells usually grow in a circular pattern in the lymph nodes.

According to the American Cancer Society (ACS), DLBCL and follicular lymphoma account for more than half of all cases of lymphoma.

Non-Hodgkin’s lymphomas can also be described in terms of how aggressive they are and the location of affected lymph nodes. NHL may be described as:

  • Indolent or aggressive
    • Indolent lymphomas, also known as low-grade lymphomas,  usually have few symptoms and grow and spread slowly.
    • Aggressive lymphomas, also known as intermediate-grade and high-grade lymphoma, usually have severe symptoms and grow and spread rapidly.
  • Contiguous or noncontiguous
    • Contiguous lymphomas are lymphomas in which the cancer containing lymph nodes are located next to each other.
    • Noncontiguous lymphomas are lymphomas in which the cancer containing lymph nodes are not next to each other, but are on the same side of the diaphragm (a muscle that separates the chest and abdominal cavities). For example, lymphomas in lymph nodes under the right arm and in the right groin area are noncontiguous.

Potential causes of NHL

Some forms of cancer are caused by DNA mutations that “turn on” oncogenes (genes that speed up cell division) or “turn off” tumor suppressor genes (genes that slow down cell division or cause cells to die at the right time). In people with non-Hodgkin’s lymphoma (NHL), these mutations are normally acquired after birth. The mutations may occur from exposure to radiation or cancer-causing chemicals, but many times the mutations occur for no apparent reason. Researchers have noted that these mutations seem to appear more often as people grow older. Age is the greatest risk factor for NHL, with more than half of the cases occurring in people over age 65. 

A mutation type that can cause NHL is a translocation. A translocation is the transfer of DNA from one chromosome to another. This abnormality can turn on oncogenes or turn off tumor suppressor genes.

In addition, the immune system appears to play a significant role in many cases of lymphoma. People with immune deficiencies are at an increased risk of developing the disease. This population can include patients with HIV infection and congenital immune deficiencies, as well as those who have undergone organ transplants. 

Although these factors may explain some cases of NHL, researchers do not yet understand how the disease develops in people with no apparent risk factors.

Risk factors for NHL

There is no single cause of non-Hodgkin’s lymphoma (NHL). Researchers have identified a number of factors that appear to place a person at higher risk for developing the disease. These risk factors include:

  • Age. Most cases of non-Hodgkin’s lymphoma occur in people who are in their 60s. Age is the greatest risk factor for this form of cancer.
  • Congenital immune deficiency diseases. Being born with an abnormal immune system increases a person’s risk of developing NHL during childhood or young adulthood.
  • Obesity. In the past, obesity was linked to a higher risk of NHL. Recent studies from the National Cancer Institute, however, have found that obesity may not increase a person’s chances of developing NHL or other malignant lymphoma.
  • Radiation. Patients who have received radiation therapy as treatment for other forms of cancer have a slightly increased risk of developing NHL later in life. This risk is greatest for those patients treated with both radiation therapy and chemotherapy. In addition, people who have survived (or lived in close proximity to) nuclear blasts and accidents have an increased risk of developing NHL.
  • Exposure to certain chemicals. Some studies have suggested a link between certain chemicals, including benzene and particular herbicides and insecticides, and an increased risk of developing NHL. Recent studies have linked exposure to PCBs (polychlorinated biphenyls) and compounds from the pesticide DDT to an increased risk for developing NHL. However, research is continuing to verify this connection.
  • Tobaccouse. Recent studies suggest that tobacco use increases the risk of developing NHL. Previous research did not link tobacco use to NHL in either women or men. However, more controlled studies in recent years have found an increased risk, particularly with heavy smokers.
  • Chemotherapy drugs. Certain chemotherapy drugs used to treat other types of cancer can increase a person’s risk of developing NHL later in life. However, a direct cause and effect relationship has not yet been proven.
  • Immunosuppressant drugs. Patients such as kidney transplant recipients being treated with immunosuppressant drugs (drugs that weaken the immune system) are at an increased risk of developing NHL. The exact increase in risk is dependent on the type of medication and the dose.
  • Human immunodeficiency virus (HIV). Being infected with HIV increases a person’s risk of developing certain types of NHL.
  • Human T-cell leukemia/lymphoma virus (HTLV-1). Being infected with HTLV–1 increases a person’s risk of developing certain types of NHL. Belonging to the same virus family as HIV, this virus is most common in the Caribbean and some parts of Japan. It is far less common in the United States, where it accounts for less than 1 percent of lymphomas.
  • Epstein-Barr virus (EBV). EBV is the virus that causes mononucleosis. In certain areas of Africa, infection with the EBV is considered an important risk factor for Burkitt’s lymphoma. EBV is a risk factor for lymphomas in people in other countries as well, particularly those infected with HIV. In addition, infection with other viruses, such as hepatitis C, also may increase the risk of NHL.
  • Infection with the parasite that causes malaria. In certain areas of Africa, infection with the parasite that causes malaria is considered an important risk factor for Burkitt’s lymphoma.
  • Helicobacter pylori. Known to cause stomach ulcers, this type of bacteria can also trigger some lymphomas of the stomach.

Although NHL is associated with these risk factors, the majority of patients with the disease have no known risk factors.

Signs and symptoms of NHL

Depending on its location in the body, non-Hodgkin’s lymphoma (NHL) can cause a variety of symptoms.

Common signs and symptoms include:

  • Enlarged lymph nodes (swollen glands) in the neck, armpits or groin
  • Unexplained weight loss
  • Fever
  • Excessive sweating, particularly at night
  • Fatigue
  • Itchiness

When NHL affects the tissue in the abdomen or stomach, common signs and symptoms include:

  • Swollen abdomen
  • Stomach or abdominal pain
  • Enlarged liver and/or spleen
  • Decreased appetite
  • Nausea 
  • Vomiting

When the disease begins in the chest, common signs and symptoms include:

  • Coughing
  • Breathing difficulty
  • SVC syndrome (narrowing of the superior vena cava vein that returns blood to the heart from the upper half of the body resulting in the swelling of the head and arms)

When the disease affects the brain, common signs and symptoms include:

  • Headache
  • Seizures
  • Mental confusion
  • Difficulty moving parts of the body
  • Personality changes

Common signs and symptoms of lymphomas of the skin include itchy red or purple lumps under the skin.

Patients experiencing any of these symptoms are encouraged to contact their physician. The earlier non-Hodgkin’s lymphoma is diagnosed, the better chance for successful treatment.

Diagnosis methods for NHL

First, a physician will obtain the patient’s medical history and perform a complete physical examination. Because infections are the most common cause of enlarged lymph nodes, the physician will examine the area surrounding the swollen lymph nodes for an infection. The physician may prescribe antibiotics and re-examine the lymph nodes in one to two weeks to determine if the lymph nodes have shrunk. If they are still enlarged or have become more swollen, a biopsy of the area may be ordered. A biopsy is the definitive method for diagnosing whether cancer is present and if so, its type and stage.

Biopsies are required to diagnose and classify non-Hodgkin’s lymphoma. The procedure involves removing a sample of lymph node tissue and sending it to a pathologist for examination. Excisional and incisional biopsies are the two procedures used to diagnose NHL. In these procedures, the physician makes an incision through the skin to remove an entire lymph node (excisional biopsy), or a small section of a large tumor (incisional biopsy). When the lymph node is located near the skin surface, the procedure is relatively simple, and can be done with local anesthesia. However, when the lymph node is inside the chest or abdomen general anesthesia is required.

A fine needle aspiration (FNA) biopsy is another type of biopsy that may be ordered. In this procedure, a thin needle and a syringe are used to remove a small amount of fluid and tissue. This procedure is useful because it does not require surgery. However, there are some disadvantages. One disadvantage is that in some situations the needle cannot remove the amount of tissue needed for a diagnosis. Advances are being made to counteract this problem. FNA is also helpful in diagnosing cancers that have spread to lymph nodes from other organs, and in distinguishing lymph nodes that are swollen by infection. 

After a diagnosis has been confirmed, the disease will be staged. Staging is the process of determining how far the cancer has spread and is necessary to determine treatment. Additional tests also may be necessary for diagnosis and treatment planning. These tests may be ordered by a medical oncologist, a physician who specializes in the diagnosis and treatment of cancers. Imaging tests that may be used during the staging of non-Hodgkin’s lymphoma include:

  • Chest x-ray. This test uses low doses of radiation to produce images of the chest on film paper or fluorescent screens. With non-Hodgkin’s lymphoma, enlarged lymph nodes may be detected in the chest.

  • CAT scan (computed axial tomography). This test allows for multiple x-rays to be taken from different angles around the patient. The cross-sectional images of the patient’s body are analyzed by a computer.  CAT scans give a physician an enhanced look at the lymph nodes in the head, neck, chest, abdomen and pelvis. They can also reveal enlarged organs, such as the liver and the spleen. CAT scans also may be used to guide a biopsy needle into an enlarged lymph node located deep in the body. This procedure is known as a CAT-guided needle biopsy.
  • MRI (magnetic resonance imaging). This test uses a powerful magnetic field to create images of structures and organs within the body allowing a computer to produce very clear cross-sectional or three-dimensional images. It may be ordered to determine if the disease has spread to the spinal cord or brain.

  • PET scan (positron emission tomography). In this procedure, the patient receives an injection of glucose (sugar) containing a small amount of radioactive material. Once in the body, the radioactive glucose is absorbed by the cancer cells. A camera then scans the patient and detects where the radioactive glucose was absorbed.

    This test is useful when a physician wants to look for lymphoma throughout the entire body. Areas where the cancer cells are present appear as hot spots. They are brighter than noncancerous areas because they absorb more radioactive glucose. PET scan can also be useful in determining whether an enlarged lymph node contains cancer or is benign.

  • Gallium scan. A patient receives an injection of gallium-67, a radioactive substance that is often absorbed by areas of the body where non-Hodgkin’s lymphoma is present. A few days after the injection, the patient is placed under a scanner that detects where the gallium has accumulated in the body and the image is recorded on film. These tests are useful for locating the disease in bones and organs. It is also useful in differentiating lymphomas from an infection.

  • Bone scan. In this procedure, a mildly radioactive substance is injected into the bloodstream where it travels to areas where bone is damaged. The test is helpful in locating bone damage due to lymphoma in the bones.

  • Ultrasound. This procedure uses harmless high-frequency sound waves to produce images of internal organs. This test is useful for uncovering masses in the abdomen and for detecting kidneys or other organs that have swollen as the result of enlarged lymph nodes.    

Additional tests that may be ordered include:

  • Bone marrow biopsy and aspiration. Usually performed together during the same procedure, a bone marrow biopsy and a bone marrow aspiration may be ordered for initial diagnosis. It also may be used to determine how far the disease has spread. A bone marrow aspiration uses a long thin needle attached to a syringe to remove small amounts of liquid bone marrow. During the biopsy, a larger needle is used to remove a narrow piece of bone. The samples are usually taken from the back of the pelvic bone after the patient has received local anesthesia.

  • Lumbar puncture. Also known as a spinal tap, this procedure uses a needle to remove a sample of cerebrospinal fluid (CSF) from between the bones in the lower spine. The sample is then examined for lymphoma cells.

  • Immunohistochemistry. Part of a biopsy sample is treated with special antibodies. The antibodies attach themselves to specific molecules on the cell surface and cause color changes that are detectable under a microscope. This test may be ordered to distinguish the various types of NHL from one another and from other diseases.

  • Flow cytometry. Fluorescent antibodies are used to detect certain molecules on the surface of lymphoma cells. The cells are treated with the antibodies, each of which attach themselves to certain types of cells. The cells are then passed in front of a laser beam which causes the cells to give off light of a different color. The color is then measured and analyzed by a computer. This test may be ordered to determine if lymph node enlargement is due to NHL or another form of cancer or disease. It is also useful in diagnosing the exact type of NHL.

  • Cytogenetics. This test uses a microscope to evaluate the characteristics of specially treated cells including their nuclear structure. It may be ordered to determine if the cells have too many chromosomes, or if the chromosomes have any translocations (the transfer of DNA from one chromosome to another).

  • Molecular genetic studies. These tests may be ordered to spot translocations of cell DNA that are not detectable under a microscope during cytogenetic testing. The tests can also detect oncogenes (genes that speed up cell division) that have been “turned on” and are contributing to the abnormal growth of the lymphoma cells.

  • Blood tests. A complete blood count and blood chemistry studies may be ordered. A complete blood count measures the number of red blood cells, white blood cells and platelets in a sample of blood, as well as the amount of hemoglobin in the red blood cells and a number of other factors. Blood chemistry studies measure the amounts of specific substances released into the blood by organs and tissues.

Treatment and prevention of NHL

As with all cancers, treatment for non-Hodgkin’s lymphoma is usually coordinated by a cancer care team. The team is composed of healthcare professionals specific for the patient’s type of cancer. For non-Hodgkin’s lymphoma, the team may include:

  • Primary physician
  • Medical oncologist
  • Radiation oncologist
  • Hematologist
  • Oncology nurse
  • Dietician
  • Social worker

Other healthcare professionals may be consulted for specific problems related to the patient’s condition.

Treatment for non-Hodgkin’s lymphoma (NHL) is based on a number of factors including the type of lymphoma and its stage. Several types of treatment are used against NHL, including:

  • Chemotherapy. This treatment method uses powerful drugs to destroy cancer cells. The drugs are typically taken orally or by injection.The most common chemotherapy for NHL is a combination of cyclophosphamide, doxorubicin, vincristine and prednisone. The acronym CHOP is used for this combination, based on several variations of the names of these four drugs.

  • Radiation therapy. Precise high-energy radiation is used to destroy cancer cells and shrink tumors. NHL is usually treated with external beam radiation, a form of radiation therapy that uses a machine located outside of the body to deliver beams of radiation at cancer cells.

A third method used to treat NHL is biological therapy or immunotherapy. This method uses substances naturally produced by the immune system to kill lymphoma cells and slow the growth of the cancer cells. It also helps activate the patient’s immune system to more successfully fight the disease. Substances that may be used include:

  • Interferon. Produced by the white blood cells, this hormone-like protein helps the immune system fight infections. Some research has suggested that treating a patient with artificially created interferon can cause certain types of NHL to shrink or stop expanding.

  • Monoclonal antibodies. Monoclonal antibodies are antibodies produced in a lab to resemble the antibodies normally produced in the body. Monoclonal antibodies are designed to attack lymphoma cells.

The most effective treatment for NHL may require one or a combination of these methods.

For some patients, high-dose chemotherapy with blood-forming stem cell transplants may be recommended. This treatment involves giving the patient very high doses of chemotherapy, followed by an infusion of blood–forming stem cells. This treatment method may be recommended to patients when standard treatment has failed. Although only a small percentage of patients with NHL are treated with this therapy, the number is growing. In 2002, the American Cancer Society (ACS) reported approximately 4,300 NHL patients in the United States received a stem cell transplant.

A nonmyeloablative transplant is another type of transplant used to treat NHL. It relies on the immune response of a donor’s cells to destroy the lymphoma. In this procedure, patients are placed on low doses of chemotherapy. They are then given stem cells from a donor. Eventually, the transplanted cells develop an immune response to the cancer cells and they begin to destroy them.   

Follow-up care is very important for NHL patients. Once treatment has been completed, the physician usually requires a physical examination every three months for one year. Frequent blood tests are used to monitor for leukemia, and other blood disorders. Additional tests, including PET scans and CAT scans, may be ordered depending on the type and location of the cancer. Patients are encouraged to report the development of any new symptoms to their physician. They may be a sign of recurrent lymphoma or side effects of treatment. The NHL may come back in the lymph system or develop in other parts of the body.

According to the American Cancer Society, the overall five-year relative survival rate for people with NHL is 63 percent. The 10-year relative survival rate is 49 percent.  Survival rates vary with the type of NHL, as well as other contributing factors.

There are no established prevention methods for non-Hodgkin’s lymphoma. Currently, the best way to prevent developing the disease is to prevent known risk factors, such as human immunodeficiency virus (HIV).

Ongoing research regarding NHL

There is a great deal of research being conducted in the area of non-Hodgkin’s lymphoma (NHL). Clinical trials and scientific studies are being conducted in cancer centers and laboratories by a number of medical groups. Areas of research for NHL include:

  • New chemotherapy drugs. A new drug treatment known as rituximab treatment has been studied with NHL patients. Studies have shown combining this drug with the common CHOP chemotherapy protocol may prolong survival in certain types of NHL. Additional drugs and delivery systems continue to be studied by a number of researchers.

  • Gene marker testing and gene therapy. Numerous studies are focusing on identifying genes that may predict NHL as well as gene therapy that can treat the condition. Researchers are examining the patterns produced by genes to help determine the new treatments and improved the prognosis. One family of proteins called protein kinase C (PKC) is being used in clinical trials.

    In addition, numerous gene studies are being conducted in the Mantle Cell Lymphoma Initiative (MCLI). Mantle cell is rare from B-cell lymphoma that has received little attention in the past. MCLI has received large funding to study this life-threatening condition.

  • Vaccines. Researchers are studying ways to develop vaccines that can help the immune system fight cancer. These vaccines are designed to create an immune reaction in patients whose disease is in remission or those with lymphoma in a very early stage. The therapy uses a substance or a combination of substances to cause the immune system to respond to the tumor and destroy it. Vaccines for lymphomas are still experimental and not yet approved by the Food and Drug Administration (FDA). Clinincal trials suggest that lymphoma vaccines may help shrink tumors and help prevent recurrence of the disease.

  • Stem cell and bone marrow transplants. Small numbers of NHL patients have undergone chemotherapy with stem cell transplants. Patients donate blood cells, which have cancer cells removed and then are returned to the patients as part of efforts to repopulate the bone marrow after massive doses of chemotherapy. Researchers are working on better methods to clean the blood cells patients donate, both to remove the cancer cells and to enrich the stem cells before returning them to the patient. Matched stem cells from other donors may be used, but matches are difficult to find. Researchers are also studying ways to reduce complications found with transplants, such as graft-versus-host disease and adverse side effects.
    New radioimmunotherapy regimens. Researchers are studying drugs that can help deliver radiation directly to the cancer cells. This combination treatment has shown promise for long-term remission of lymphoma.

  • Complementary and alternative therapy approaches

Staging of non-Hodgkin’s lymphoma

The staging system for non-Hodgkin’s lymphoma (NHL) consists of four categories. Depending on how far the cancer has spread, the disease will be placed in either stage I, II, III or IV. The letter “E” is added to the stage when an organ outside of the lymph system is affected. 

Stage I. Non-Hodgkin’s lymphoma is considered to be at stage I when one of the following factors is present:

  • The cancer is found in only one lymph node area such as the neck, armpit or groin.

  • The cancer is found in only one area of a single organ outside of the lymph system (IE).

Stage II. NHL is considered to be at stage II when one of the following factors is present:

  • The cancer is found in two or more lymph node areas on the same side (above or below) of the diaphragm (a muscle that separates the chest and abdominal cavities, and aids breathing).

  • The cancer has spread locally from the lymph nodes into nearby tissue (IIE).

Stage III. NHL is considered to be at stage III when one of the following factors is present:

  • The cancer is found in lymph node areas on both sides (above and below) of the diaphragm.

  • The cancer may have spread into an organ or area next to the lymph node (IIIE), into the spleen (IIIS), or both (IIISE).

Stage IV. NHL is considered to be at stage IV when one of the following factors is present:

  • The cancer has extended to more than one area in an organ or to two or more organs outside of the lymph system.

  • The cancer has extended to only one organ outside of the lymph system, but lymph nodes far from the organ are involved.

  • The cancer has extended to the brain, spinal cord, liver or bone marrow.

These stages may be further separated into “A” (symptoms are not present) and “B” (certain symptoms are present) categories. A patient is placed in the “B” category when the following symptoms are present:

  • A loss of more than 10 percent of total body weight over the previous six months

  • A fever at or above 100 degrees Fahrenheit (38 degrees Celsius) without a known cause (except the cancer)

  • Drenching night sweats

The international prognostic index (IPI) was developed to aid physicians in predicting how quickly a patient’s lymphoma would grow, whether treatment is needed, and how well a patient would react to treatment. This information is important to physicians who are planning treatment. The index also provides patients with information about the outlook for their disease.

The index is based on five factors:

  • Age

  • Stage of the disease

  • Whether or not organs outside of the lymph system are affected

  • Performance status (how well a patient can perform normal daily activities)

  • Level of lactate dehydrogenase (LDH) in the blood serum

The factors are then divided into either good prognostic factors or poor prognostic factors.

 Good prognostic factorsPoor prognostic factors
Age60 or belowAbove 60
Stage of lymphomaI or IIIII or IV
Lymphoma is present outside of the lymph nodesNoYes
Performance statusNormal daily functionDifficulty with daily function
Serum LDH levelNormalHigh

For each poor prognostic factor that a patient has, they are given one point. More than 75 percent of the people with no points or one point live longer than five years, regardless of the type of lymphoma. In contrast, only 30 percent of those with most or all unfavorable factors live longer than five years.

Questions for your doctor about NHL

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their condition. Patients may wish to ask their doctor the following questions about non-Hodgkin’s lymphoma (NHL):

  1. Am I at risk for developing NHL?
  2. What symptoms indicate that I might have NHL?
  3. What tests will be used to diagnose my condition?
  4. What type of biopsy will I need?
  5. How will it be performed?
  6. When and from whom will I learn the biopsy results?
  7. What is my prognostic index?
  8. What are my treatment options?
  9. What are the risks associated with these treatments?
  10. Will I benefit from a bone marrow transplant?
  11. Can I donate my own cells? If not, who can be a donor?
  12. At what point in treatment would I receive the transplant?
  13. What are the chances my cancer will return following treatment?
  14. How will my health be monitored after treatment?
  15. Am I a candidate for a clinical trial?
  16. Am I at greater risk for other cancers?
  17. What is the difference between NHL and Hodgkin’s lymphoma?
  18. Will my children have a greater risk of developing NHL?
  19. Should we consider genetic testing?
  20. Can you recommend an NHL support group?
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