Section 14. Blood Disorders

Chapter 177. Lymphomas

Topics: Introduction | Hodgkin's Disease | Non-Hodgkin's Lymphomas

Non-Hodgkin's Lymphomas

Non-Hodgkin's lymphomas are a diverse group of cancers that develop in B or T lymphocytes.

This group of cancers is actually more than 20 different diseases, which have distinct appearances under the microscope, different cell patterns, and different clinical courses. Most non-Hodgkin's lymphomas (85%) are from B cells; less than 15% develop from T cells. Non-Hodgkin's lymphoma is more common than Hodgkin's disease. In the United States, about 65,000 new cases are diagnosed every year, and the number of new cases is increasing, especially among older people and people whose immune system is not functioning normally. Those at risk include people who have had organ transplants and some people who have been infected with the human immunodeficiency virus (HIV).

Although the cause of non-Hodgkin's lymphoma is not known, evidence strongly supports a role for viruses in some of the less common types of non-Hodgkin's lymphomas. A rare type of rapidly progressive non-Hodgkin's lymphoma, which occurs in southern Japan and the Caribbean, may result from infection with human T-cell lymphotropic virus type I (HTLV-I), a retrovirus similar to HIV. The Epstein-Barr virus is the cause of many cases of Burkitt's lymphoma, another type of non-Hodgkin's lymphoma.

See the sidebar Unusual Non-Hodgkin's Lymphomas.

Symptoms

The first symptom is often painless enlargement of lymph nodes in the neck, under the arms, or in the groin. Enlarged lymph nodes within the chest may press against airways, causing cough and difficulty in breathing. Deep lymph nodes within the abdomen may press against various organs, causing loss of appetite, constipation, abdominal pain, or progressive swelling of the legs.

Since some lymphomas can appear in the bloodstream and bone marrow, people can develop symptoms related to too few red blood cells, white blood cells, or platelets. Too few red blood cells can cause anemia; and the person may have fatigue, shortness of breath, and pale skin. Too few white blood cells can lead to infections. Too few platelets may lead to increased bruising or bleeding. Non-Hodgkin's lymphomas also commonly invade the bone marrow, digestive tract, skin, and occasionally the nervous system, causing a variety of symptoms. Some people have persistent fever without an evident cause, the so-called fever of unknown origin. This commonly reflects an advanced stage of disease.

In children, the first symptoms--anemia, rashes, and neurologic symptoms, such as weakness and abnormal sensation--are likely to be caused by infiltration of lymphoma cells into the bone marrow, blood, skin, intestine, brain, and spinal cord. Lymph nodes that become enlarged are usually deep ones, leading to accumulation of fluid around the lungs, which causes difficulty in breathing; pressure on the intestine, which causes loss of appetite or vomiting; and blocked lymph vessels, which causes fluid retention, most noticeably in the arms and legs.

See the table Symptoms of Non-Hodgkin's Lymphoma.

Diagnosis and Classification

Doctors perform a biopsy of an enlarged lymph node to diagnose non-Hodgkin's lymphoma and to distinguish it from Hodgkin's disease and other problems that cause enlarged lymph nodes.

Although more than 20 different diseases can be called non-Hodgkin's lymphoma, doctors sometimes group them into three broad categories. Indolent lymphomas are characterized by a survival of many years even when a person does not undergo treatment. Aggressive lymphomas are characterized by survival limited to several months in someone who goes untreated. Highly aggressive lymphomas are characterized by survival of only weeks when a person does not undergo treatment. Although non-Hodgkin's lymphomas are usually diseases of middle-aged and older people, children and young adults may develop lymphomas, and these lymphomas are commonly more aggressive.

Staging

Many people with a non-Hodgkin's lymphoma have disease that has spread at the time of diagnosis. In only 10 to 30% of people, the disease is limited to one specific area. People with the disease undergo similar staging procedures as those with Hodgkin's disease (see Section 14, Chapter 177). In addition, a bone marrow biopsy is almost always performed.

Treatment and Prognosis

Almost everyone benefits from treatment. For some people, complete cure is possible; for others, treatment extends life and relieves symptoms for many years. The likelihood of cure or long-term survival depends on the type of non-Hodgkin's lymphoma and the stage when treatment starts. It is somewhat of a paradox that indolent lymphomas usually respond readily to treatment by going into remission (in which the disease is under control), often followed by long-term survival, but the disease usually is not cured. In contrast, aggressive and highly aggressive non-Hodgkin's lymphomas, which usually require very intensive treatment to achieve remission, have a good chance of being cured.

Stage I and II Non-Hodgkin's Lymphomas: People with indolent lymphomas who have very limited disease (stages I and II) are often treated with radiation limited to the site of the lymphoma and adjacent areas. With this approach, 20 to 30% of people may have long-term remission and are probably cured. People with aggressive or highly aggressive lymphomas at a very early stage need to be treated with combinations of chemotherapy, often with the addition of localized radiation therapy. With this approach, 70 to 90% of people are cured.

Stage III and IV Non-Hodgkin's Lymphomas: Almost all people with indolent lymphomas have stage III or IV disease. They do not always require treatment, but they are closely monitored for evidence of complications that could signal more rapid progression of the disease. There is no evidence that early treatment in people with indolent lymphomas at more advanced stages extends survival. If the disease begins to progress more rapidly, there are many treatment choices.

Treatment may include chemotherapy with a single drug or as a combination of several different drugs. No treatment is clearly superior, so the choice of treatment is influenced by the extent of disease and the symptoms a person is having. Treatment usually produces a remission, but the average length of remission ranges from 2 to 4 years. A decision about treatment after a relapse (in which lymphoma cells reappear) again depends on the extent of the disease and the symptoms. After an initial relapse, remissions tend to become shorter.

Many new treatments are now available for indolent lymphomas. These include monoclonal antibodies, which bind to lymphoma cells and kill them. These antibodies (immunoglobulins), such as rituximab, are given intravenously. Sometimes, the monoclonal antibodies are modified so that they can carry radioactive particles or toxic chemicals directly to the cancer cells in different parts of the body. It remains uncertain whether these monoclonal antibodies can cure non-Hodgkin's lymphomas, or if they can achieve better results when combined with chemotherapy.

Another new approach to treating indolent lymphomas involves vaccinating the person with proteins taken from his own lymphoma. The person's immune system recognizes the proteins as "foreign" and then fights the lymphoma in much the same way that it fights an infection.

For people with aggressive or highly aggressive stage III or IV non-Hodgkin's lymphomas, combinations of chemotherapy drugs are given promptly. Many potentially effective combinations of chemotherapy drugs are available. Combinations of chemotherapy drugs are often given names created by using single letters from each of the drugs that are included. For example, one of the oldest and still most commonly used combinations is known as CHOP (cyclophosphamide, [hydroxy]doxorubicin, vincristine [Oncovin], and prednisone). About 50% of people with aggressive or highly aggressive non-Hodgkin's lymphomas at an advanced stage are cured with CHOP chemotherapy. Newer combinations of drugs have not produced much improvement in cure rates. However, chemotherapy, which often causes different types of blood cells to decrease in number, is sometimes better tolerated if special proteins (called growth factors) are given to stimulate growth and development of blood cells. Chemotherapy for some people with aggressive or highly aggressive lymphomas is now combined with monoclonal antibodies. For example, results from the combination of CHOP with rituximab may be better than from CHOP alone, but studies are still ongoing.

Chemotherapy at usual doses is of very limited value when relapse occurs. Many people who have a relapse of an aggressive or highly aggressive lymphoma at an advanced stage receive high-dose chemotherapy combined with autologous stem cell transplantation, involving the person's own stem cells (see Section 16, Chapter 187). With this type of treatment, up to 40% of people may be cured. Some stem cell transplants for people with an aggressive or highly aggressive lymphoma use stem cells from a matched or unrelated donor (allogeneic transplant), but this type of transplantation has a greater risk of complications.