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non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma is cancer of a type of white blood cell in the lymphatic system. The lymphatic system drains fluid from tissue and returns it to the blood. It plays an important role in the body's defence against infection.

Non-Hodgkin's lymphoma is classified in several ways. One practical way to classify the disease is by how fast it grows. In this scheme, there are three grades: low-grade, intermediate-grade, and high-grade. Low-grade is the slowest growing, and high-grade is the fastest.

What is going on in the body?
Non-Hodgkin's lymphoma begins in one type of lymph tissue. It starts either in the lymph nodes, the spleen, the bone marrow, or other, less common lymph tissues. The malignant cells involved can be of the slow growing, low-grade variety. Or the cells can be extremely active and fast growing, and can cause death in a short period.

There are many types of white blood cells in the body. Lymphoma cells usually lose their normal immune, or infection-fighting, function. A lymphoma can involve B lymphocytes, which make antibodies that attack viruses and bacteria. Or it can involve T lymphocytes, which make immune proteins and communicate between different parts of the immune system. Other lymph cells may be involved, including non-T and non-B lymphocytes, natural killer cells, and null cells. Any of these can become malignant. In non-Hodgkin's lymphoma, usually only one kind of white blood cell becomes cancerous.

Lymphoma cells grow and cause lymph nodes and internal organs to enlarge. The lymphoma cells also infiltrate and crowd out the bone marrow. They can invade any other part of the body, including the brain, lungs, kidneys, the skin, the hard part of the bone, the intestines, or even the heart. Lymphomas can also cause immune system problems and unusual infections.

Autoimmune disorders are common. Autoimmunity means that the body's immune system attacks itself. This can occur in any area of the body, and can lead to kidney failure, anaemia, blood clots, bleeding, arthritis, or nerve damage.

Lymphoma occurs in all age groups and both sexes. Some subtypes are more common in elderly people, and others are more common in young people. The different subtypes have different rates of response and cure. Most subtypes respond to some form of treatment.

What are the signs and symptoms of the disease?
Some lymphomas grow slowly and cause few problems besides enlarged lymph nodes. Lymph nodes are small, round glands found all over the body. They can become enlarged in people without lymphomas who have an infection. In a lymphoma, the lymph nodes are usually not tender. They can be very large, and may feel firm or rubbery. Other symptoms include:
  • fatigue
  • unexplained fevers
  • night sweats
  • weight loss
  • skin lesions
  • signs of anaemia
  • unusual infections
  • easy bruising or abnormal bleeding
  • abdominal distress
  • bone pain
What are the causes and risks of the disease?
Lymphoma occurs when the genes of a white blood cell change enough that the cell grows uncontrollably. How this occurs is an important part of cancer research. Many of the genes that become abnormal and control this cell growth have been described. The exact process, as well as why some people develop lymphoma and others do not, continue to be part of the cancer question.

Some of the risk factors for non-Hodgkin's lymphoma are:
  • exposure to radiation or certain viruses
  • inherited or acquired deficiencies of the immune system such as acquired immunodeficiency syndrome or AIDS
  • treatments that suppress the immune system, such as chemotherapy, corticosteroids, or the drugs given after organ transplantation such as heart transplants, liver transplants or lung transplants
Some autoimmune disorders may increase the risk of Non-Hodgkin's lymphoma. Tobacco use does not seem to be a strong risk factor. There is controversy over whether some pesticides or herbicides can cause lymphoma.

What can be done to prevent the disease?
It's important to avoid radiation and toxins in the environment. These toxins include pesticides, insecticides, and solvents. There is no proof that the diet is important in preventing lymphoma. People whose medical problems put them at risk of developing lymphoma should see a doctor regularly.

How is the disease diagnosed?
Lymphoma is diagnosed by biopsies, or the examining of tissue samples. Blood samples are taken so that immune studies can be done on white blood cells. Some lymphomas cause higher levels of white cells in the blood, but others do not.

Bone marrow biopsies and lymph node biopsies are usually used to make a diagnosis. Lymphomas are classified into different subtypes based on their characteristics. This classification of lymphomas continues to evolve as knowledge of the disease advances.

Lymphomas need to be staged, which is rough measure of the amount of cancer in the body. These evaluations can help to determine the stage of the disease: Lymphoma stages are classified as I, II, III, and IV. This classification scheme is like the one for Hodgkin's disease, another type of lymphoma.
  • Stage I is limited to one lymph node area in the body.
  • Stage II involves two lymph node areas that are next to each other.
  • Stage III involves lymph node areas on both sides of the diaphragm, the muscular flap that separates the chest from the abdomen.
  • Stage IV, the worst stage, involves widespread disease. Other organs, such as the liver, spleen, bone marrow, bone, lung, central nervous system, or skin, are affected.
Staging does not predict treatment outcomes like it does in Hodgkin's disease. In non-Hodgkin's lymphoma, a better predictor is the type of tissue involved.

Special laboratory testing called immune analysis can help predict the outcome of lymphoma. This analysis looks at cell proteins and gene abnormalities. It does not always help if figuring out which treatment to use, though.

What are the long-term effects of the disease?
Long-term effects of non-Hodgkin's lymphoma depend on the histology, or cell type.

What are the risks to others?
Lymphoma is not contagious. There are no risks to others.

What are the treatments for the disease?
Surgery is sometimes needed, but it is not considered a cure. Surgery can relieve problems caused by lymphoma, such as obstructions in the bowels or blood vessels, and spinal cord or nerve compression.

Radiation therapy is used to ease symptoms and as a potential cure. Early-stage lymphoma limited to one lymph node area can sometimes be cured with radiation alone. But radiation therapy alone does not work well on more advanced lymphomas. Radiation therapy is also used to shrink bothersome lymph nodes or other masses.

Lymphoma tends to be a total-body or systemic disease. So chemotherapy is the mainstay of treatment. The exact medications, doses, duration of treatment, and combination with radiation therapy depend on the type of lymphoma.

High-grade lymphomas are treated with intensive high-dose intravenous (IV) chemotherapy. This approach is sometimes used for intermediate-grade lymphomas, too. Methotrexate, vincristine, vinblastine, etoposide (VP-16), and many other drugs are used. These medications are given in cycles for several weeks to several months. People are usually treated as outpatients unless other medical problems arise.

Low-grade lymphomas are treated when problems occur. The problems usually result from long-term treatment with immune therapy or low-dose chemotherapy drugs, such as cladribine (2-cda) or fludarabine. It's not known for sure whether this disease can be cured with medical treatment. The problem has been that the disease recurs after treatment, and the recurrence is harder to treat. Lymphoma may need to be treated with high-dose chemotherapy, total-body or total-lymph node radiation, and bone marrow transplantation.

Immune therapy is giving a person manufactured proteins and other substances often made by a normal immune system. It's a new and evolving kind of treatment. Interferons, interleukins, monoclonal antibodies, immune toxins, or radiolabeled immune proteins may be given. Lymphomas are quite sensitive to chemotherapy, so many new drugs are being tried.

What are the side effects of the treatments?
Lymphoma is also quite sensitive to radiation therapy, so very high doses usually are not needed. Radiation tends to cause local effects. Some temporary effects are skin burning, irritation of the nearby organs, bone marrow suppression, hair loss, nausea, and fatigue. Permanent damage to organs can also occur, including scarring of the lungs or intestines, or weakening of the heart. The areas of skin affected by radiation can become darker, and secondary cancers can develop. Some immune therapy can cause a flu-like illness, heart or kidney failure, or skin rashes.

Chemotherapy can have both temporary and permanent side effects. Treatment for low-grade lymphomas usually has few side effects. IV chemotherapy may cause nausea and vomiting, hair loss, mouth sores, diarrhoea, constipation, fatigue and bone marrow suppression. There is also a risk of infection or bleeding problems. Any organ in the body can be damaged, depending on the medications used.

Combining chemotherapy and radiation therapy increases the side effects of both. Suppression of the immune system from these treatments can be short-lived or last for several months. People who get bone marrow transplants may not have normal immune systems again for several years. Side effects of new, experimental new medications can be unpredictable.

What happens after treatment for the disease?
Some low-grade lymphomas are treated only to lessen the symptoms. Treatment is stopped when the benefits do not outweigh the side effects. Some of these people may need to be treated periodically. Other lymphomas are considered curable. Some high-grade lymphomas have a 60 to 80 percent cure rate.

How is the disease monitored?
People are monitored to watch for recurrence of the disease, and to treat any complications. Monitoring methods are similar to those used in initial staging of the disease. Physical examinations, blood tests, biopsies, x-rays, and CAT scans may be needed. Special genetic tests can be done on blood or bone marrow specimens. These tests are very good at detecting any remaining disease or early recurrence.

Author: Thomas Fisher, MD
Reviewer: HealthAnswers Australia Medical Review Panel
Editor: Dr David Taylor, Chief Medical Officer HealthAnswers Australia
Last Updated: 1/10/2001
Potential conflict of interest information for reviewers available on request

This website and article is not a substitute for independent professional advice. Nothing contained in this website is intended to be used as medical advice and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice.  All Health and any associated parties do not accept any liability for any injury, loss or damage incurred by use of or reliance on the information.


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