Non-Hodgkin's lymphoma

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Non-Hodgkin lymphoma is a type of cancer arising from lymphocytes, a type of white blood cells. It is so called because of its distinction from Hodgkin's disease, a particular subtype of lymphoma. It is in fact an overarching term of many different forms of lymphoma, each with individual characteristics.

Lymphomas may develop in any organ associated with the lymphatic system (e.g. spleen, and tonsils). Most cases start with infiltration of lymph nodes (nodal), but specific subtypes may be restricted to the lymphatic organs (e.g.spleen, thymus, and tonsils).

Diagnosis of lymphoma requires biopsy of involved tissue. Before treatment, a common method to decide on treatment is called "watch and wait". "Watch and wait" is when doctors judge the case of NHL and how it is affecting the patient before deciding on a treatment option. Treatment of indolent or low-grade lymphoma may be supportive, while aggressive high-grade non-Hodgkin lymphoma is typically treated with chemotherapy and often with radiation therapy.


The most common symptom of non-Hodgkin's lymphoma is a painless swelling of the lymph nodes in the neck, underarm (axilla), or groin.

Other symptoms may include the following:

When symptoms like these occur, they are not sure signs of non-Hodgkin's lymphoma. They may also be caused by other, less serious conditions, such as the flu or other infections. Only a doctor can make a diagnosis. When symptoms are present, it is important to see a doctor so that any illness can be diagnosed and treated as early as possible. Do not wait to feel pain; early non-Hodgkin's lymphoma may not cause pain.


If non-Hodgkin's lymphoma is suspected, the doctor asks about the person's medical history and performs a physical exam. The exam includes feeling to see if the lymph nodes in the neck, underarm, or groin are enlarged. In addition to checking general signs of health, the doctor may perform blood tests.

The doctor may also order tests that produce pictures of the inside of the body. These may include:

  • X-rays: Pictures of areas inside the body created by high-energy radiation.
  • CT scan (computed tomography scan, also known as a "CAT scan"): A series of detailed pictures of areas inside the body. The pictures are created by a computer linked to an x-ray machine.
  • PET scan (positron emission tomography scan): This is an imaging test that detects uptake of a radioactive tracer by the tumor. More often, the PET scan can be combined with the CT scan.
  • MRI (magnetic resonance imaging): Detailed pictures of areas inside the body produced with a powerful magnet linked to a computer.
  • Lymphangiogram: Pictures of the lymphatic system taken with x-rays after a special dye is injected to outline the lymph nodes and vessels. This test is not used as often because of the adoption of CT scan and the PET scan technologies

A biopsy is needed to make a diagnosis. A surgeon removes a sample of tissue so that a pathologist can examine it under a microscope to check for cancer cells. A biopsy for non-Hodgkin's lymphoma is usually taken from lymph nodes that are enlarged, but other tissues may be sampled as well. Rarely, an operation called a laparotomy may be performed. During this operation, a surgeon cuts into the abdomen and removes samples of tissue to be checked under a microscope.

Types of non-Hodgkin's lymphoma

Over the years, doctors have used a variety of terms to classify the many different types of non-Hodgkin's lymphoma. Most often, they are grouped by how the cancer cells look under a microscope and how quickly they are likely to grow and spread. Aggressive lymphomas, also known as intermediate and high-grade lymphomas, tend to grow and spread quickly and cause severe symptoms. Indolent lymphomas, also referred to as low-grade lymphomas, tend to grow quite slowly and cause fewer symptoms. One of the paradoxes of non-Hodgkin's lymphoma is that the indolent lymphomas generally cannot be cured by chemotherapy, while in a significant number of cases aggressive lymphomas can be. Current lymphoma classification is complex. Common types of lymphomas include follicular lymphoma and diffuse large B cell lymphoma.

Details of the most popular classifications of lymphoma can be found in the lymphoma page.


The etiology, or cause, of most lymphomas is not known. Some types of lymphomas are associated with viruses. Burkitt's lymphoma, extranodal NK/T cell lymphoma, classical Hodgkin's disease and most AIDS-related lymphoma are associated with Epstein-Barr virus. Adult T-cell lymphoma/leukemia, endemic in parts of Japan and the Caribbean, is caused by the HTLV-1 virus. Lymphoma of the stomach (extranodal marginal zone B-cell lymphoma) is often caused by the Helicobacter bacteria.

The incidence of non-Hodgkin's lymphoma has increased dramatically over the last couple of decades. This disease has gone from being relatively rare to being the fifth most common cancer in the United States. At this time, little is known about the reasons for this increase or about exactly what causes non-Hodgkin's lymphoma.

Doctors can seldom explain why one person gets non-Hodgkin's lymphoma and another does not. It is clear, however, that cancer is not caused by an injury, and is not contagious; no one can "catch" non-Hodgkin's lymphoma from another person.

By studying patterns of cancer in the population, researchers have found certain risk factors that are more common in people who get non-Hodgkin's lymphoma than in those who do not. However, most people with these risk factors do not get non-Hodgkin's lymphoma, and many who do get this disease have none of the known risk factors.

The following are some of the risk factors associated with this disease:

  • Age/Sex -- The likelihood of getting non-Hodgkin's lymphoma increases with age and is more common in men than in women.
  • Weakened Immune System (AIDS-related lymphoma) -- Non-Hodgkin's lymphoma is more common among people with inherited immune deficiencies, autoimmune diseases, or HIV/AIDS, and among people taking immunosuppressant drugs following organ transplants. (see Post-transplant lymphoproliferative disorder)
  • Viruses -- Human T-lymphotropic virus type I (HTLV-1) and Epstein-Barr virus are two infectious agents that increase the chance of developing non-Hodgkin's lymphoma.
  • Environment -- People who work extensively with or are otherwise exposed to certain chemicals, such as pesticides, solvents, or fertilizers, have a greater chance of developing non-Hodgkin's lymphoma.

People who are concerned about non-Hodgkin's lymphoma should talk with their doctor about the disease, the symptoms to watch for, and an appropriate schedule for checkups. The doctor's advice will be based on the person's age, medical history, and other factors.


If non-Hodgkin's lymphoma is diagnosed, the doctor needs to learn the stage, or extent, of the disease. Staging is a careful attempt to find out whether the cancer has spread and, if so, what parts of the body are affected. Treatment decisions depend on these findings.

The doctor considers the following to determine the stage of non-Hodgkin's lymphoma:

  • The number and location of affected lymph nodes;
  • Whether the affected lymph nodes are above, below, or on both sides of the diaphragm (the thin muscle under the lungs and heart that separates the chest from the abdomen); and
  • Whether the disease has spread to the bone marrow, spleen, or to organs outside the lymphatic system, such as the liver.

In staging, the doctor may use some of the same tests used for the diagnosis of non-Hodgkin's lymphoma. Other staging procedures may include additional biopsies of lymph nodes, the liver, bone marrow, or other tissue. A bone marrow biopsy involves removing a sample of bone marrow through a needle inserted into the hip or another large bone. A pathologist examines the sample under a microscope to check for cancer cells.

Stages of NHL

The various stages of NHL (the Ann Arbor staging classification, developed for Hodgkin's lymphoma) are based on how far the cancer has spread throughout and beyond the lymphatic system, and whether constitutional symptoms (fever, night sweats, or weight loss) are present.

Stage I
"Stage I" indicates that the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.
Stage II
"Stage II" indicates that the cancer is located in two separate regions, an affected lymph node or organ within the lymphatic system and a second affected area, and that both affected areas are confined to one side of the diaphragm - that is, both are above the diaphragm, or both are below the diaphragm.
Stage III
"Stage III" indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.
Stage IV
"Stage IV" indicates that the cancer has spread beyond the lymphatic system and involves one or more major organs, possibly including the bone marrow or skin.

The absence of constitutional symptoms is denoted by adding an "A" to the stage; the presence is denoted by adding a "B" to the stage.

Staging in Non-Hodkin's lymphomas is far less significant in determining therapy than it is in Hodgkin's lymphoma.


The doctor develops a treatment plan to fit each patient's needs. Treatment for non-Hodgkin's lymphoma depends on the stage of the disease, the type of cells involved, whether they are indolent or aggressive, and the age and general health of the patient.

Non-Hodgkin's lymphoma is often treated by a team of specialists that may include a hematologist, medical oncologist, and/or radiation oncologist. Non-Hodgkin's lymphoma is usually treated with chemotherapy, radiation therapy, or a combination of these treatments. In some cases, bone marrow transplantation, biological therapies, or surgery may be options. For indolent lymphomas, the doctor may decide to wait until the disease causes symptoms before starting treatment. Often, this approach is called "watchful waiting."

Taking part in a clinical trial (research study) to evaluate promising new ways to treat non-Hodgkin's lymphoma is an important option for many people with this disease.

Chemotherapy and radiation therapy are the most common treatments for non-Hodgkin's lymphoma, although bone marrow transplantation, biological therapies, or surgery are sometimes used. CHOP, with rituximab added in certain circumstances, is the most commonly used combination of chemotherapy.

Radiation therapy (also called radiotherapy) is the use of high-energy rays to kill cancer cells. Treatment with radiation may be given alone or with chemotherapy. Radiation therapy is local treatment; it affects cancer cells only in the treated area. Radiation therapy for non-Hodgkin's lymphoma comes from a machine that aims the high-energy rays at a specific area of the body. There is no radioactivity in the body when the treatment is over.

Sometimes patients are given chemotherapy and/or radiation therapy to kill undetected cancer cells that may be present in the central nervous system (CNS). In this treatment, called central nervous system prophylaxis, the doctor injects anticancer drugs directly into the cerebrospinal fluid.

Bone marrow transplantation (BMT) may also be a treatment option, especially for patients whose non-Hodgkin's lymphoma has recurred (come back). BMT provides the patient with healthy stem cells (very immature cells that produce blood cells) to replace cells damaged or destroyed by treatment with very high doses of chemotherapy and/or radiation therapy. The healthy bone marrow may come from a donor, or it may be marrow that was removed from the patient, treated to destroy cancer cells, stored, and then given back to the person following the high-dose treatment. Until the transplanted bone marrow begins to produce enough white blood cells, patients have to be carefully protected from infection. They usually stay in the hospital for several weeks.

Biological therapy (also called immunotherapy) is a form of treatment that uses the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that can be caused by some cancer treatments. It uses materials made by the body or made in a laboratory to boost, direct, or restore the body's natural defenses against disease. Biological therapy is sometimes also called biological response modifier therapy.

Measuring Response to Treatment

After treatment for non-Hodgkin lymphoma, the response is classified as follows:

  • Complete Response (CR). This indicates the disappearance of all detectable disease.
  • Partial Response (PR). A reduction in the bulk of disease by at least 50%, but with some remaining disease.
  • Stable Disease. Less than a partial remission, but no progression of disease and no new sites of disease.
  • Progressive Disease. Growth in bulk of disease by >50%, or the appearance of new sites of disease.

If a complete remission is acheived, the patient is watched closely for any evidence of recurrent disease. By convention, if a patient remains in complete remission for 5 years, they are felt to be cured. While disease relapses can happen more than 5 years out, it is very uncommon.

If the response to treatment falls short of a complete response, more treatment may be administered (using a different chemotherapy regimen), or watchful waiting may be utilized, depending on the goals of treatment.

Clinical trials

Many people with non-Hodgkin's lymphoma take part in clinical trials (research studies). Doctors conduct clinical trials to learn about the effectiveness and side effects of new treatments. In some trials, all patients receive the new treatment. In others, doctors compare different therapies by giving the new treatment to one group of patients and the standard therapy to another group; or they may compare one standard treatment with another. Research like this has led to significant advances in the treatment of cancer. Each achievement brings researchers closer to the eventual control of cancer.

Doctors are studying radiation therapy, new ways of giving chemotherapy, new anticancer drugs and drug combinations, biological therapies, bone marrow transplantation, peripheral blood stem cell transplantation, and new ways of combining various types of treatment. Some studies are designed to find ways to reduce the side effects of treatment and to improve the patient's quality of life.


Eating well during cancer treatment means getting enough food energy and protein to help prevent weight loss and regain strength. Good nutrition often helps people feel better and have more energy.

Some people with cancer find it hard to eat a balanced diet because they may lose their appetite. In addition, common side effects of treatment, such as nausea, vomiting, or mouth sores, can make eating difficult. Often, foods may taste or smell different. Also, people being treated for cancer may not feel like eating when they are uncomfortable or tired.

Doctors, nurses, and dietitians can offer advice on how to get enough food energy and protein during cancer treatment. Patients and their families also may want to read the National Cancer Institute (USA) booklet Eating Hints for Cancer Patients, which contains many useful suggestions.


The most significant factor in overall prognosis is the grade, or aggressiveness, of the lymphoma. Indolent (low-grade) non-Hodgkin lymphoma is generally not curable, but is typically slowly progressive and responds temporarily to therapy. Aggressive and highly aggressive (intermediate- and high-grade) NHL's are potentially curable with combination chemotherapy. Long-term survival or cure rates for these diseases vary with a number of prognostic factors.

International Prognostic Index

The International Prognostic Index, or IPI, is the most widely used prognostic system for non-Hodgkin lymphoma. This system uses 5 factors:

  • Age
  • Lactate dehydrogenase level (a blood test)
  • Performance status
  • Clinical stage
  • Sites of extranodal disease

However, it should be noted that the IPI was developed prior to the introduction of rituximab. As rituximab has become a standard part of therapy for B-cell NHL's, the impact on the prognostic value of the IPI is unclear.


For the subtype of NHL known as follicular lymphoma, a modified version of the IPI called the FLIPI (follicular lymphoma international prognostic index) has been developed. The factors which figure into the FLIPI are age, clinical stage, lactate dehydrogenase level, hemoglobin level, and number of nodal sites involved. As with the IPI, the FLIPI was developed and validated prior to the widespread use of rituximab, so the same caveats apply as were mentioned with the IPI above.

Followup care

People who have had non-Hodgkin's lymphoma should have regular followup examinations after their treatment is over. Followup care is an important part of the overall treatment plan, and people should not hesitate to discuss it with their health care provider. Regular followup care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between followup appointments, people who have had non-Hodgkin's lymphoma should report any health problems as soon as they appear.

Notable NHL patients

Notable persons treated for Non-Hodgkin's lymphoma include:

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