Malignant Lymphomas

Definition

Lymphomas are a group of cancers in which cells of the lymphatic system become abnormal and start to grow uncontrollably. Because there is lymph tissue in many parts of the body, lymphomas can start in almost any organ of the body.

Description

The lymph system is made up of ducts or tubules that carry lymph to all parts of the body. Lymph is a milky fluid that contains the lymphocytes or white blood cells. These are the infection-fighting cells of the blood. Small pea-shaped organs are found along the network of lymph vessels. These are called the lymph nodes, and their main function is to make and store the lymphocytes. Clusters of lymph nodes are found in the pelvis region, underarm, neck, chest, and abdomen. The spleen (an organ in the upper abdomen), the tonsils, and the thymus (a small organ found beneath the breastbone) are part of the lymphatic system.

The lymphocyte is the main cell of the lymphoid tissue. There are two main types of lymphocytes: the T lymphocyte and the B lymphocyte. Lymphomas develop from these two cell types. B cell lymphomas are more common among adults, while among children, the incidence of T and B cell lymphomas are almost equal.

The T and the B cell perform different jobs within the immune system. When an infectious bacterium enters the body, the B cell makes proteins called "antibodies." These antibodies attach themselves to the bacteria, and flag them for destruction by other immune cells. The T cells help protect the body against viruses. When a virus enters the cell, it generally produces certain proteins that are projected on the surface of the infected cell. T cells recognize these proteins and produce certain substances (cytokines) that destroy the infected cells. Some of the cytokines made by the T cells attract other cell types, which are capable of digesting the virus-infected cell. The T cells can also destroy some types of cancerous cells.

Lymphomas can be divided into two main types: Hodgkin's lymphoma or Hodgkin's disease, and non-Hodgkin's lymphomas. There are at least 10 types of non-Hodgkin's lymphomas. They are grouped (staged) by how aggressively they grow; slow growing (low grade), intermediate growing, and rapidly growing (high grade); and how far they spread.

A majority of non-Hodgkin's lymphomas begin in the lymph nodes. About 20% start in other organs, such as the lungs, liver or the gastrointestinal tract. Malignant lymphocytes multiply uncontrollably and do not perform their normal functions. Hence, the body's ability to fight infections is affected. In addition, these malignant cells may crowd the bone marrow, and, depending on the stage, prevent the production of normal red blood cells, white blood cells, and platelets. A low red blood cell count causes anemia, while a reduction in the number of platelets makes the person susceptible to excessive bleeding. Cancerous cells can also invade other organs through the circulatory system of the lymph, causing those organs to malfunction.

Causes and symptoms

The exact cause of non-Hodgkin's lymphomas is not known. However, the incidence has increased significantly in the recent years. Part of the increase is due to the AIDS epidemic. Individuals infected with the AIDS virus have a higher likelihood of developing non-Hodgkin's lymphomas. In general, males are at a higher risk for having non-Hodgkin's lymphomas than are females. The risk increases with age. Though it can strike people as young as 40, people between the ages of 60 and 69 are at the highest risk.

People exposed to certain pesticides and ionizing radiation have a higher than average chance of developing this disease. For example, an increased incidence of lymphomas has been seen in survivors of the atomic bomb explosion in Hiroshima, and in people who have undergone aggressive radiation therapy. People who suffer from immune-deficient disorders, as well as those who have been treated with immune suppressive drugs for heart or kidney transplants, and for conditions such as rheumatoid arthritis and autoimmune diseases, are at an increased risk for this disease.

There have been some studies that have shown a loose association between retroviruses, such as HTLV-I, and some rare forms of lymphoma. The Epstein-Barr virus has been linked to Burkitt's lymphoma in African countries. However, a direct cause-and-effect relationship has not been established.

The symptoms of lymphomas are often vague and non-specific. Patients may experience loss of appetite, weight loss, nausea, vomiting, abdominal discomfort, and indigestion. The patient may complain of a feeling of fullness, which is a result of enlarged lymph nodes in the abdomen. Pressure or pain in the lower back is another symptom. In the advanced stages, the patient may have bone pain, headaches, constant coughing, and abnormal pressure and congestion in the face, neck, and upper chest. Some may have fevers and night sweats. In most cases, patients go to the doctor because of the presence of swollen glands in the neck, armpits, or groin area. Since all the symptoms are common to many other illnesses, it is essential to seek medical attention if any of the conditions persist for two weeks or more. Only a qualified physician can correctly diagnose if the symptoms are due to lymphoma or some other ailment.

Diagnosis

Like all cancers, lymphomas are best treated when found early. However, it is often difficult to diagnose lymphomas. There are no screening tests available, and, since the symptoms are non-specific, lymphomas are rarely recognized in their early stages. Detection often occurs by chance during a routine physical examination.

When the doctor suspects lymphoma, a complete medical history is taken, and a thorough physical examination is performed. Enlargement of the lymph nodes, liver, or spleen may suggest lymphomas. Blood tests will determine the cell counts and obtain information on how well the organs, such as the kidney and liver, are functioning.

A biopsy of the enlarged lymph node is the most definitive diagnostic tool for staging purposes. The doctor may perform a bone marrow biopsy. During the biopsy, a cylindrical piece of bone and marrow fluid is removed. They are generally taken out of the hipbone. These samples are sent to the laboratory for examination. In addition to diagnosis, the biopsy may also be repeated during the treatment phase of the disease to see if the lymphoma is responding to therapy.

Once the exact form of lymphoma is known, it is then staged to determine how aggressive it is, and how far it has spread. Staging is necessary to plan appropriate treatment.

Conventional imaging tests, such as x rays, computed tomography scans (CT scans), magnetic resonance imaging, and abdominal sonograms, are used to determine the extent of spread of the disease.

Lymphangiograms are x rays of the lymphatic system. In this procedure, a special dye is injected into the lymphatic channels through a small cut (incision) made in each foot. The dye is injected slowly over a period of three to four hours. This dye clearly outlines the lymphatic system and allows it to stand out. Multiple x rays are then taken and any abnormality, if present, is revealed.

Rarely, a lumbar puncture or a spinal tap is performed to check if malignant cells are present in the fluid surrounding the brain. In this test, the physician inserts a needle into the epidural space at the base of the spine and collects a small amount of spinal fluid for microscopic examination.

Treatment

Treatment options for lymphomas depend on the type of lymphoma and its present stage. In most cases, treatment consists of chemotherapy, radiotherapy, or a combination of the two methods.

Chemotherapy is the use of anti-cancer drugs to kill cancer cells. In non-Hodgkin's lymphomas, combination therapy, which involves the use of multiple drugs, has been found more effective than single drug use. The treatment may last about six months, but in some cases may last as long as a year. The drugs may either be administered intravenously (through a vein) in the arm or given orally in the form of pills. If cancer cells have invaded the central nervous system, then chemotherapeutic drugs may be instilled, through a needle in the brain or back, into the fluid that surrounds the brain. This procedure is known as intrathecal chemotherapy.

Radiation therapy, where high-energy ionizing rays are directed at specific portions of the body, such as the upper chest, abdomen, pelvis, or neck, is often used for treatment of lymphomas. External radiation therapy, where the rays are directed from a source outside the body, is the most common mode of radiation treatment.

Bone marrow transplantation is used in cases where the lymphomas do not respond to conventional therapy, or in cases where the patient has had a relapse or suffers from recurrent lymphomas.

There are two ways of doing bone marrow transplantation. In a procedure called "allogeneic bone marrow transplant," a donor is found whose marrow matches that of the patient. The donor can be a twin (best match), a sibling, or a person who is not related at all. High-dose chemotherapy or radiation therapy is given to eradicate the lymphoma. The donor marrow is then given to replace the marrow destroyed by the therapy.

In "autologous bone marrow transplantation," some of the patient's own bone marrow is harvested, chemically purged, and frozen. High-dose chemotherapy and radiation therapy are given. The marrow that was harvested, purged, and frozen is then thawed and put back into the patient's body to replace the destroyed marrow.

A new treatment option for patients with lymphoma is known as "peripheral stem cell transplantation." In this treatment approach, cells that normally circulate in the blood are collected when the patient has normal blood counts taken, and these cells are saved via a process called "pheresis." Researchers are exploring whether these cells can be used to restore the normal function and development of blood cells, rather than using a bone marrow transplant.

Prognosis

Like all cancers, the prognosis for lymphoma depends on the stage of the cancer, and the patient's age and general health. When all the different types and stages of lymphoma are considered together, only 50% of patients survive 5 years or more after initial diagnosis. This is because some types of lymphoma are more aggressive than others.

The survival rate among children is definitely better than among older people. About 90% of the children diagnosed with early stage disease survive 5 years or more, while only 60-70% of adults diagnosed with low grade lymphomas survive for 5 years or more. The survival rate for children with the more advanced stages is about 75-85%, while among adults it is 40-60%.

Prevention

Although many cancers may be prevented by making diet and life style changes which reduce risk factors, there is currently no known way to prevent lymphomas. Protecting oneself from developing AIDS, which may be a risk factor for lymphomas, is the only preventive measure that can be practiced.

At present, there are no special tests that are available for early detection of non-Hodgkin's lymphomas. Paying prompt attention to the signs and symptoms of this disease, and seeing a doctor if the symptoms persist, are the best strategies for an early diagnosis of lymphoma. Early detection affords the best chance for a cure.

KEY TERMS

Antibodies— Proteins made by the B lymphocytes in response to the presence of infectious agents such as bacteria or viruses in the body.

Biopsy— The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Growth factors (cytokines)— Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors."

Resources

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta, GA 30329-4251. (800) 227-2345. 〈http://www.cancer.org〉.

Cancer Research Institute. 681 Fifth Ave., New York, N.Y. 10022. (800) 992-2623. 〈http://www.cancerresearch.org〉.

Leukemia Society of America, Inc. 600 Third Ave., New York, NY 10016. (800) 955 4572. 〈http://www.leukemia.org〉.

Lymphoma Research Foundation. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204 7040.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 422-6237. 〈http://www.nci.nih.gov〉.

Oncolink. University of Pennsylvania Cancer Center. 〈http://cancer.med.upenn.edu〉.

OTHER

"Adults Non-Hodgkin's Lymphoma." National Cancer Institute Page. 〈http://www.nci.nih.gov〉.

"Childhood Non-Hodgkin's Lymphoma." National Cancer Institute Page. 〈http://www.nci.nih.gov〉.

"Hodgkin's Disease" and Non-Hodgkin's Lymphoma." The Leukemia Society. 〈http://www.leukemialymphoma.org/hm_lls〉.

Malignant lymphoma

Definition

Lymphomas are a group of cancers in which cells of the lymphatic system become abnormal and start to grow uncontrollably. Because there is lymph tissue in many parts of the body, lymphomas can start in almost any organ of the body.

Description

The lymphatic system is made up of ducts or tubules that carry lymph to all parts of the body. Lymph is a milky fluid that contains lymphocytes. These, along with monocytes and granulocytes make up the leukocytes, or white blood cells, the infection-fighting and reparative bodies in the blood. Small pea-shaped organs found along the network of lymph vessels are called lymph nodes; their main function is to make and store lymphocytes. Clusters of lymph nodes are found in the pelvic region, underarm, neck, chest, and abdomen. The spleen (an organ in the upper abdomen), the tonsils, and the thymus (a small organ beneath the breastbone) are also part of the lymphatic system. Lymphocytes are held within the lymphoid tissue until they join the flow of lymph through the node. There are two main types of lymphocytes: the T cell and the B cell. Lymphomas develop from these two types. B-cell lymphomas are more common among adults, while among children, the incidence of T- and B-cell lymphomas are almost equal.

The T and the B cells perform different jobs within the immune system. When an infectious bacterium enters the body, the B cells make proteins called antibodies, which attach themselves to the bacteria, and flag them for destruction by other immune cells. The T cells help protect the body against viruses. When a virus enters a cell, it generally produces certain proteins that it projects onto the surface of the infected cell. T cells recognize these proteins and produce cytokines to destroy the infected cells. Some cytokines attract other cell types, which can digest the virus-infected cell. T cells can also destroy some types of cancer cells.

Lymphomas can be divided into two main types: Hodgkin's and non-Hodgkin's. There are at least 10 types of non-Hodgkin's lymphomas that are grouped (staged) by how aggressively they grow: slow growing (low grade), intermediate growing, and rapidly growing (high grade); and how far they spread.

Most non-Hodgkin's lymphomas begin in the lymph nodes; about 20% start in other organs, such as the lungs, liver or gastrointestinal tract. When lymphomas begin, malignant lymphocytes multiply uncontrollably and do not perform their normal functions, which affects the body's ability to fight infections . In addition, malignant cells may crowd the bone marrow, and, depending on the stage, prevent the production of normal red blood cells, white blood cells, and platelets. A low red blood cell count causes anemia , while a reduction in the number of platelets makes the person susceptible to excessive bleeding. Cancerous cells can also invade other organs through the circulatory system of the lymph, causing those organs to malfunction.

Causes & symptoms

The exact cause of non-Hodgkin's lymphomas is unknown. In general, males are at a higher risk than females, and the risk increases with age. Though it can strike people as young as 40, people between the ages of 60 and 69 are at the highest risk. In addition, the number of non-Hodgkin's cases has increased significantly in recent years, many of them due to the AIDS epidemic. (For reasons that are still poorly understood, AIDS patients have a higher likelihood of developing non-Hodgkin's lymphomas.)

People exposed to certain pesticides and ionizing radiation have a higher-than-average chance of developing this disease. For example, an increased incidence of lymphomas has been seen in survivors of the atomic bomb explosion in Hiroshima, and in people who have under-gone aggressive radiation therapy. People who suffer from immune-deficient disorders, as well as those who have been treated with immune-suppressive drugs for heart or kidney transplants, and for conditions such as rheumatoid arthritis and autoimmune diseases, are at an increased risk for this disease. Some studies have shown a loose association between retroviruses, such as HTLV-I, and some rare forms of lymphoma. The Epstein-Barr virus has been linked to Burkitt's lymphoma in African countries. However, a direct cause- and-effect relationship has not been established.

The symptoms of lymphomas are often vague and nonspecific. Patients may experience loss of appetite, weight loss, nausea, vomiting , abdominal discomfort, and indigestion . The patient may complain of a feeling of fullness, which is a result of enlarged lymph nodes in the abdomen. Pressure or pain in the lower back is another symptom. In the advanced stages, the patient may have bone pain, headaches, constant coughing, and abnormal pressure and congestion in the face, neck, and upper chest. Some may have fevers and night sweats. In most cases, patients go to the doctor because of the presence of swollen glands in the neck, armpits, or groin area. Since all the symptoms are common to many other illnesses, it is essential to seek medical attention if any of the conditions persist for two weeks or more. Only a qualified physician can correctly diagnose if the symptoms are due to lymphoma or some other ailment.

Diagnosis

Like all cancers, lymphomas are best treated when found early. However, they are often difficult to diagnose. There are no screening tests available, and, since the symptoms are nonspecific, lymphomas are rarely recognized in their early stages. Detection often occurs by chance during a routine physical examination.

When the doctor suspects lymphoma, a thorough physical examination is performed and a complete medical history taken. Enlarged liver, spleen, or lymph nodes may suggest lymphomas. Blood tests will determine the cell counts and obtain information on how well the organs, such as the kidney and liver, are functioning.

A biopsy (microscopic tissue analysis) of the enlarged lymph node is the most definitive way to diagnose a lymphoma. Once the exact form of lymphoma is known, it is then staged to determine how aggressive it is, and how far it has spread. This information helps determine the appropriate treatment. The doctor may also perform a bone marrow biopsy. During this procedure, a cylindrical piece of bone—generally from the hip—and marrow fluid are removed. These samples are sent to the laboratory for examination. Biopsies may also be repeated during treatment to see how the lymphoma is responding to therapy.

Conventional imaging tests, such as x rays, computed tomography scans (CT scans), magnetic resonance imaging, and abdominal sonograms, are used to determine the extent of spread of the disease. Lymphangiograms are x rays of the lymphatic system. In this procedure, a special dye, called contrast medium, is injected into the lymphatic channels through a small incision (cut) made in each foot. The dye is injected slowly over a period of three to four hours. This dye clearly outlines the lymphatic system and allows it to stand out. Multiple x rays are then taken and any abnormality, if present, is revealed.

In rare cases a lumbar puncture (spinal tap) is performed to see if malignant cells are in the fluid that surrounds the brain. In this test, the physician inserts a needle into the epidural space at the base of the spine and collects a small amount of spinal fluid for microscopic examination.

Treatment

Non-Hodgkin's lymphoma is a life-threatening disease, and a correct diagnosis and appropriate treatment with surgery, chemotherapy, and/or radiation are critical to controlling the illness.

Acupuncture, hypnotherapy , and guided imagery may be useful tools in treating the pain of lymphomas. Acupuncture uses a series of thin needles placed in the skin at targeted locations known as acupoints; in theory, this harmonizes the energy flow within the body, and may help improve immune system function.

In guided imagery, patients create pleasant and soothing mental images that promote relaxation and improve their ability to cope with discomfort and pain. Another guided-imagery technique involves creating a mental picture of pain. Once the pain is visualized, patients can adjust the image to make it more pleasing, and thus more manageable.

Herbal remedies, such as Chinese herbs and mushroom extracts, may also lessen pain and promote relaxation and healing. Some herbs, such as ginger , are effective in the treatment of nausea caused by chemotherapy, and others, such as astragalus , help build the immune system. Check with an herbal practitioner before deciding on treatment. Depending on the preparation and the type of herb, the remedies may interfere with other prescribed medications. Naturally, any other activities that promote well-being, such as exercise, stress reduction, meditation, yoga, t'ai chi , and qigong will also benefit the patient. Proper nutrition and some specialized diets may help in recovering from lymphomas.

Allopathic treatment

Treatment options for lymphomas depend on the type of lymphoma and its stage. In most cases, treatment consists of chemotherapy, radiation therapy, or a combination of the two.

Chemotherapy uses anticancer drugs to kill cancer cells. In non-Hodgkin's lymphomas, combination therapy, which uses several drugs, has been found more effective than single-drug use. Treatment usually lasts about six months, but in some cases may be as long as a year. The drugs are administered intravenously (through a vein) or given orally. If cancer cells have invaded the central nervous system, then chemotherapeutic drugs may be instilled, through a needle in the brain or back, into the fluid that surrounds the brain. This procedure is known as intrathecal chemotherapy.

Radiation therapy, where high-energy ionizing rays are directed at specific portions of the body, such as the upper chest, abdomen, pelvis, or neck, is often used for treatment of lymphomas. External radiation therapy, where the rays are directed from a source outside the body, is the most common mode of radiation treatment.

Bone marrow transplantation is being tested as a treatment option when lymphomas do not respond to conventional therapy, or when the patient has had a relapse or suffers from recurrent lymphomas. There are two ways of doing bone marrow transplantation. In a procedure called allogeneic bone marrow transplant, the donor's marrow must match that of the patient. The donor can be a twin (best match), sibling, or not related at all. High-dose chemotherapy or radiation therapy is given to eradicate the lymphoma. The donor marrow is then given to replace the marrow destroyed by the therapy. In autologous bone marrow transplantation some of the patient's own marrow is harvested, chemically purged, and frozen. High-dose chemotherapy and radiation therapy are administered. The marrow that was harvested, purged, and frozen is then thawed and put back into the patient's body to replace the destroyed marrow.

A new option for lymphoma patients is peripheral stem cell transplantation. In this treatment, stem cells (immature cells from which all blood cells develop), that normally circulate in the blood are collected, treated to remove cancer cells, then returned to the patient in a process called leukapheresis. Researchers are exploring whether these cells can be used to restore the normal function and development of blood cells, rather than using a bone marrow transplant.

Expected results

Like all cancers, the prognosis for lymphoma patients depends on the stage of the cancer, and the patient's age and general health. When all the different types and stages of lymphoma are considered together, only 50% of patients survive five years or more after initial diagnosis. This is because some types of lymphoma are more aggressive than other types. The survival rate among children is definitely better than among older people. About 90% of children diagnosed with early-stage disease survive five years or more, while only 60-70% of adults diagnosed with low-grade lymphomas survive for five years or more. The survival rate for children with the more advanced stages is about 75-85%, while among adults it is 40-60%.

Prevention

Although the risk of developing cancer can be reduced by making wise diet and lifestyle choices, there is currently no known way to prevent lymphomas, nor are there special tests that allow early detection. Paying prompt attention to the signs and symptoms of this disease, and seeing a doctor if the symptoms persist, are the best strategies for an early diagnosis, which affords the best chance for a cure.

Resources

BOOKS

Dollinger, Malin, et al. Everyone's Guide to Cancer Therapy. Kansas City: Andrews McKeel Publishing, 1997.

Fauci, Anthony, et al., eds. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 1998.

Murphy, Gerald P. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. New York: American Cancer Society, 1997.

PERIODICALS

"Alternative Cancer Therapies Popular Today." Cancer. 77, no. 6 (March 1996).

ORGANIZATIONS

American Cancer Society (National Headquarters). 1599 Clifton Road, N.E. Atlanta, GA 30329. (800) 227-2345. http://www.cancer.org.

Cancer Research Institute (National Headquarters). 681 Fifth Avenue, New York, NY 10022. (800) 992-2623. http://www.cancerresearch.org.

The Lymphoma Research Foundation of America, Inc. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204-7040. http://www.lymphoma.org.

National Cancer Institute. 9000 Rockville Pike, Building 31, room 10A16, Bethesda, MD 20892. (800) 422-6237. http://www.nci.nih.gov.

Paula Ford-Martin

Malignant lymphomas

Definition

Malignant lymphomas are a group of cancers in which cells of the lymphatic system become abnormal and start to grow uncontrollably and spread (metastasize) throughout the body. Because lymph tissue is in many parts of the body, lymphomas can start in almost any organ of the body. Lymphomas are classified as being either non-Hodgkin's lymphoma or Hodgkin's disease.

Description

The lymph system is made up of ducts or tubules that carry lymph to all parts of the body. Lymph is a milky fluid that contains the lymphocytes or white blood cells, as well as protein and waste products. These are the infection-fighting cells of the blood. Small pea-shaped organs are found along the network of lymph vessels. These are called the lymph nodes, and their main function is to make and store lymphocytes. Clusters of lymph nodes are found in the pelvis region, underarm, neck, chest, and abdomen. The spleen, the tonsils, and the thymus are part of the lymphatic system.

The lymphocyte is the main cell of the lymphoid tissue. There are two main types of lymphocytes: the T lymphocyte and the B lymphocyte. Lymphomas develop from these two cell types. B cell lymphomas are more common among adults; while among children, the incidence of T and B cell lymphomas is almost equal.

The T and the B cell perform different jobs within the immune system . When an infectious bacterium enters the body, the B cell makes proteins called "antibodies." These antibodies attach themselves to the bacteria and flag them for destruction by other immune cells. The T cells help protect the body against viruses . When a virus enters the cell, it generally produces certain proteins that are projected on the surface of the infected cell. T cells recognize these proteins and produce certain substances (cytokines) that destroy the infected cells. Some of the cytokines made by the T cells attract other cell types, which are capable of digesting the virus-infected cell. The T cells can also destroy some types of cancerous cells.

Lymphomas can be divided into two main types: Hodgkin's lymphoma or Hodgkin's disease, and non-Hodgkin's lymphomas. The two are distinguished by cell type and have similar symptoms. Non-Hodgkin's lymphomas are more common, with at least 30 different types. Hodgkin's primarily affects individuals 15–40 years of age, while Non-Hodgkin's occurs mainly in persons between the ages of 30–70.

Lymphomas are grouped (staged) by how aggressively they grow—slow growing (low grade, mostly found in B-cell types), intermediate growing (seen in both B-cell and T-cell types), and rapidly growing (high grade, seen in both B-cell and T-cell types)—and how far they spread. Lymphomas are also staged by the Roman numerals I, II, III, and IV. These stages indicate the following:

• Stage I. There is only one cancer site. No bone marrow involvement found.
• Stage II. Two sites are found, either above or below the diaphragm. There is no bone marrow involvement.
• Stage III. Sites are found above and below the diaphragm, but there is still no bone marrow involvement.
• Stage IV. The bone marrow is involved and the cancer cells have metastasized beyond the lymphatic system.

A majority of non-Hodgkin's lymphomas begin in the lymph nodes. About 20% start in other organs, such as the lungs , liver , or the gastrointestinal tract. Malignant lymphocytes multiply uncontrollably and do not perform their normal functions. Hence, the body's ability to fight infections is affected. In addition, these malignant cells may crowd the bone marrow and, depending on the stage,

prevent the production of normal red blood cells, white blood cells, and platelets. A low red blood cell count causes anemia, while a reduction in the number of platelets makes the person susceptible to excessive bleeding. Cancerous cells can also invade other organs through the circulatory system of the lymph, causing those organs to malfunction.

In 2001, an estimated 56,200 Americans received a diagnosis of non-Hodgkin's lymphoma, and approximately 16,300 people died from malignant lymphomas. It is the fifth most common cancer in the country (not including nonmelanoma skin cancers). The incidence of non-Hodgkin's lymphoma has nearly doubled since the 1970s; however, during the 1990s the rate began to decline. The increase was related both to an actual increase in the number of cases as well as improved methods of detecting the disease. Over 95% of non-Hodgkin's lymphomas occur in adults, with the average age at diagnosis being in the early 40s. The disease more commonly occurs in men than women, and whites are affected to a greater extent than Asian Americans or African Americans.

Causes and symptoms

The exact cause of non-Hodgkin's lymphomas is not known. However, the incidence has increased significantly in recent years. Part of the increase is due to the AIDS epidemic. Individuals infected with the AIDS virus have a higher likelihood of developing non-Hodgkin's lymphomas.

People exposed to certain pesticides and ionizing radiation have a higher than average chance of developing this disease. For example, an increased incidence of lymphomas has been seen in survivors of the atomic bomb explosion in Hiroshima, and in people who have undergone aggressive radiation therapy. People who suffer from immune-deficient (immunodeficiency ) disorders and those who have been treated with immune suppressive drugs for transplants or for conditions such as rheumatoid arthritis and autoimmune diseases are at an increased risk for this disease.

Some studies have shown a loose association between retroviruses, such as HTLV-I, and some rare forms of lymphoma. The Epstein-Barr virus has been linked to Burkitt's lymphoma in African countries. However, a direct cause-and-effect relationship has not been established.

The symptoms of lymphomas are often vague and non-specific. The signs and symptoms may differ, depending on the location of the involvement. Patients may experience loss of appetite, weight loss, nausea, vomiting, abdominal discomfort, and indigestion. The patient may complain of a feeling of fullness, which is a result of enlarged lymph nodes in the abdomen. Sometimes the abdomen can become so swollen it may resemble pregnancy in a woman. Pressure or pain in the lower back is another symptom. In the advanced stages, the patient may have bone pain, headaches, constant coughing, and abnormal pressure and congestion in the face, neck, and upper chest. Some may have fevers and night sweats. In most cases, patients go to the doctor because of the presence of swollen glands in the neck, armpits, or groin area. Since all the symptoms are common to many other illnesses, it is essential to seek medical attention if any of the conditions persist for two weeks or more. Only a qualified physician can correctly diagnose whether the symptoms are due to lymphoma or some other ailment.

Diagnosis

Like all cancers, lymphomas are best treated when found early. However, it is often difficult to diagnose lymphomas. There are no screening tests available; and, since the symptoms are non-specific, lymphomas are rarely recognized in their early stages. Detection often occurs by chance during a routine physical examination .

When the doctor suspects lymphoma, a complete medical history is taken and a thorough physical examination is performed. Enlargement of the lymph nodes, liver, or spleen may suggest lymphomas. Blood tests will determine the cell counts and obtain information on how well the organs, such as the kidney and liver, are functioning.

A biopsy of the enlarged lymph node is the most definitive diagnostic tool for staging purposes. The doctor may perform a bone marrow biopsy. During the biopsy, a cylindrical piece of bone and marrow fluid is removed. They are generally taken out of the hipbone. These samples are sent to the laboratory for examination. In addition to diagnosis, the biopsy may also be repeated during the treatment phase of the disease to see if the lymphoma is responding to therapy.

Once the exact form of lymphoma is known, it is then staged to determine how aggressive it is, and how far it has spread. Staging is necessary to plan appropriate treatment.

Conventional imaging tests, such as x rays, computed tomography scans (CT scans ), magnetic resonance imaging (MRI), and abdominal sonograms, are used to determine how far the disease has spread.

Rarely, a lumbar puncture or a spinal tap is performed to check if malignant cells are present in the fluid surrounding the brain . In this test, the physician inserts a needle into the epidural space at the base of the spine and collects a small amount of spinal fluid for microscopic examination.

Treatment

Much progress has been made in the treatment of non-Hodgkin's lymphoma. Treatment options for lymphomas depend on the type of lymphoma and its present stage. In most cases, treatment consists of chemotherapy , radiotherapy , or a combination of the two methods.

Chemotherapy is the use of anti-cancer drugs to kill cancer cells. In non-Hodgkin's lymphomas, combination therapy, which involves the use of multiple drugs, has been found more effective than single drug use. The treatment may last about six months, but in some cases may last as long as a year. The drugs may either be administered intravenously or given orally in the form of pills. If cancer cells have invaded the central nervous system , then chemotherapeutic drugs may be injected, through a needle in the brain or back, into the fluid that surrounds the brain. This procedure is known as intrathecal chemotherapy.

Radiation therapy, where high-energy ionizing rays are directed at specific portions of the body, such as the upper chest, abdomen, pelvis, or neck, is often used for treatment of lymphomas. External radiation therapy, where the rays are directed from a source outside the body, is the most common mode of radiation treatment.

Stem cell transplantation is used in cases where the lymphomas do not respond to conventional therapy, or in cases where the patient has had a relapse or suffers from recurrent lymphomas. However, one study done in the Netherlands suggested that patients may do just as well with a standard chemotherapy regimen rather than the transplant.

There are two ways of performing stem cell transplantation. In a procedure called "allogeneic stem cell transplant," a donor is found whose cells match that of the patient. The donor can be a twin (best match), a sibling, or a person who is not related at all. High-dose chemotherapy or radiation therapy is given to eradicate the lymphoma. The donor stem cells are then given to replace those destroyed by the therapy.

In "autologous stem cell transplantation," some of the patient's own stem cells are collected, "purged" of lymphoma cells, and frozen. High-dose chemotherapy and radiation therapy are given. The stem cells that were taken and frozen are then thawed and put back into the patient's body to replace the destroyed marrow. One of the serious risks of autologous stem cell transplants is that it is possible for some of the lymphoma cells to remain even after purging the stem cells.

There are no proven alternative treatments for non-Hodgkin's lymphoma. However, many complementary therapies, including vitamins and herbal remedies, massage, and acupuncture, may help persons going through treatment to better cope with the side effects they might experience. Because many of these therapies have not been studied thoroughly, it is not known which ones may be potentially harmful or helpful. Therefore, the patient with lymphoma should be advised to speak with their health care professional prior to trying any alternative or complementary treatment.

Prognosis

Like all cancers, the prognosis for lymphoma depends on the stage of the cancer, and the patient's age and general health. When all the different types and stages of lymphoma are considered together, only 50% of patients survive five years or more after initial diagnosis. This is because some types of lymphoma are more aggressive than others. Patients with T-cell lymphomas generally have a worse prognosis than those with B-cell types.

The five-year survival rate for those with non-Hodgkin's lymphoma rose from 31% in 1960 to 51% in 1994. The overall survival rate among children, 78%, is definitely better than among older people. About 90% of the children diagnosed with early stage disease survive five years or more, while only 60%–70% of adults diagnosed with low grade lymphomas survive for five years or more.

KEY TERMS

Antibodies —Proteins made by the B lymphocytes in response to the presence of infectious agents such as bacteria or viruses in the body.

Autoimmune disease —A disease caused by a person's own antibodies or T cells that attack molecules, cells, or tissues.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Growth factors (cytokines) —Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors."

Metastasize —The spread of a disease, such as a cancer, from its original site to another part of the body.

Health care team roles

Many members of the health care team will work with the lymphoma patient. The primary physician may initially suspect lymphoma and order the appropriate diagnostic workup. The surgeon performs the biopsy, and the pathologist confirms the cellular diagnosis. Various x-ray and lab technicians will perform other imaging studies. Specially trained nurses administer chemotherapy and will instruct the patient on all aspects of his diagnosis and treatment. The patient may see both a medical and radiation oncologist, depending upon the specifics of the treatment ordered. Registered nurses also provide part-time family education.

Prevention

Although many cancers may be prevented by making diet and life style changes which reduce risk factors, there is currently no known way to prevent lymphomas. Protecting oneself from developing AIDS, which may be a risk factor for lymphomas, is the only preventive measure that can be practiced.

No special tests are available for early detection of non-Hodgkin's lymphomas. Paying prompt attention to the signs and symptoms of this disease and seeing a doctor if the symptoms persist are the best strategies for an early diagnosis of lymphoma. Early detection affords the best chance for a cure.

Resources

BOOKS

Beers, Mark H. and Robert Berkow, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck and Company, Inc., 1999.

PERIODICALS

"Bexxar Highly Effective First-Line Treatment" Vaccine Weekly (June 7, 2000).

Gottlieb, Scott. "Bone Marrow Transplants Show No Benefit For Non-Hodgkin's Lymphoma" British Medical Journal (January 20, 2001): 127.

ORGANIZATIONS

American Cancer Society. (800) ACS-2345. <http://www.cancer.org>.

The Leukemia and Lymphoma Society of America, Inc. 1311 Mamaroneck Ave, White Plains, NY 10605. (914)949-5213. <http://www.leukemia-lymphoma.org>.

Lymphoma Research Foundation. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310)204-7040. <http://www.lymphoma.org>.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580.(800)4CANCER. <http://www.nci.nih.gov>.

Deanna Swartout-Corbeil, R.N.

Malignant Lymphomas

Definition

Malignant lymphomas are a group of cancers in which cells of the lymphatic system become abnormal and start to grow uncontrollably and spread (metastasize) throughout the body. Because lymph tissue is in many parts of the body, lymphomas can start in almost any organ of the body. Lymphomas are classified as being either non-Hodgkin's lymphoma or Hodgkin's disease.

Description

The lymph system is made up of ducts or tubules that carry lymph to all parts of the body. Lymph is a milky fluid that contains the lymphocytes or white blood cells, as well as protein and waste products. These are the infection-fighting cells of the blood. Small pea-shaped organs are found along the network of lymph vessels. These are called the lymph nodes, and their main function is to make and store lymphocytes. Clusters of lymph nodes are found in the pelvis region, underarm, neck, chest, and abdomen. The spleen, the tonsils, and the thymus are part of the lymphatic system.

The lymphocyte is the main cell of the lymphoid tissue. There are two main types of lymphocytes: the T lymphocyte and the B lymphocyte. Lymphomas develop from these two cell types. B cell lymphomas are more common among adults; while among children, the incidence of T and B cell lymphomas is almost equal.

The T and the B cell perform different jobs within the immune system . When an infectious bacterium enters the body, the B cell makes proteins called “antibodies.” These antibodies attach themselves to the bacteria and flag them for destruction by other immune cells. The T cells help protect the body against viruses . When a virus enters the cell, it generally produces certain proteins that are projected on the surface of the infected cell. T cells recognize these proteins and produce certain substances (cytokines) that destroy the infected cells. Some of the cytokines made by the T cells attract other cell types, which are capable of digesting the virus-infected cell. The T cells can also destroy some types of cancerous cells.

Lymphomas can be divided into two main types: Hodgkin's lymphoma or Hodgkin's disease, and non Hodgkin's lymphomas. The two are distinguished by cell type and have similar symptoms. Non-Hodgkin's lymphomas are more common, with at least 30 different types. Hodgkin's primarily affects individuals between 15–40 years of age, while Non-Hodgkin's occurs mainly in persons between the ages of 30–70.

Lymphomas are grouped (staged) by how aggressively they grow—slow growing (low grade, mostly found in B-cell types), intermediate growing (seen in both B-cell and T-cell types), and rapidly growing (high grade, seen in both B-cell and T-cell types)—and how far they spread. Lymphomas are also staged by the Roman numerals I, II, III, and IV. These stages indicate the following:

• Stage I. There is only one cancer site. No bone marrow involvement found.
• Stage II. Two sites are found, either above or below the diaphragm. There is no bone marrow involvement.
• Stage III. Sites are found above and below the diaphragm, but there is still no bone marrow involvement.
• Stage IV. The bone marrow is involved and the cancer cells have metastasized beyond the lymphatic system.

A majority of non-Hodgkin's lymphomas begin in the lymph nodes. About 20% start in other organs, such as the lungs, liver, or the gastrointestinal tract. Malignant lymphocytes multiply uncontrollably and do not perform their normal functions. Hence, the body's ability to fight infections is affected. In addition, these malignant cells may crowd the bone marrow and, depending on the stage, prevent the production of normal red blood cells, white blood cells, and platelets. A low red blood cell count causes anemia , while a reduction in the number of platelets makes the person susceptible to excessive bleeding. Cancerous cells can also invade other organs through the circulatory system of the lymph, causing those organs to malfunction.

In 2001, an estimated 56,200 Americans received a diagnosis of non-Hodgkin's lymphoma, and approximately 16,300 people died from malignant lymphomas. It is the fifth most common cancer in the country (not including nonmelanoma skin cancers). The incidence of non-Hodgkin's lymphoma has nearly doubled since the 1970s; however, during the 1990s the rate began to decline. The increase was related both to an actual increase in the number of cases as well as improved methods of detecting the disease. Over 95% of non-Hodgkin's lymphomas occur in adults, with the average age at diagnosis being in the early 40s. The disease more commonly occurs in men than women, and whites are affected to a greater extent than Asian Americans or African Americans.

Causes and symptoms

The exact cause of non-Hodgkin's lymphomas is not known. However, the incidence has increased significantly in recent years. Part of the increase is due to the AIDS epidemic. Individuals infected with the AIDS virus have a higher likelihood of developing non-Hodgkin's lymphomas.

People exposed to certain pesticides and ionizing radiation have a higher than average chance of developing this disease. For example, an increased incidence of lymphomas has been seen in survivors of the atomic bomb explosion in Hiroshima, and in people who have undergone aggressive radiation therapy. People who suffer from immune-deficient (immunodeficiency) disorders and those who have been treated with immune suppressive drugs for transplants or for conditions such as rheumatoid arthritis and autoimmune diseases are at an increased risk for this disease.

Some studies have shown a loose association between retroviruses, such as HTLV-I, and some rare forms of lymphoma. The Epstein-Barr virus has been linked to Burkitt's lymphoma in African countries. However, a direct cause-and-effect relationship has not been established.

The symptoms of lymphomas are often vague and non-specific. The signs and symptoms may differ, depending on the location of the involvement. Patients may experience loss of appetite, weight loss , nausea, vomiting, abdominal discomfort, and indigestion. The patient may complain of a feeling of fullness, which is a result of enlarged lymph nodes in the abdomen. Sometimes the abdomen can become so swollen it may resemble pregnancy in a woman. Pressure or pain in the lower back is another symptom. In the advanced stages, the patient may have bone pain, headaches , constant coughing, and abnormal pressure and congestion in the face, neck, and upper chest. Some may have fevers and night sweats. In most cases, patients go to the doctor because of the presence of swollen glands in the neck, armpits, or groin area. Since all the symptoms are common to many other illnesses, it is essential to seek medical attention if any of the conditions persist for two weeks or more. Only a qualified physician can correctly diagnose whether the symptoms are due to lymphoma or some other ailment.

Diagnosis

Like all cancers, lymphomas are best treated when found early. However, it is often difficult to diagnose lymphomas. There are no screening tests available; and, since the symptoms are non-specific, lymphomas are rarely recognized in their early stages. Detection often occurs by chance during a routine physical examination.

When the doctor suspects lymphoma, a complete medical history is taken and a thorough physical examination is performed. Enlargement of the lymph nodes, liver, or spleen may suggest lymphomas. Blood tests will determine the cell counts and obtain information on how well the organs, such as the kidney and liver, are functioning.

A biopsy of the enlarged lymph node is the most definitive diagnostic tool for staging purposes. The doctor may perform a bone marrow biopsy . During the biopsy, a cylindrical piece of bone and marrow fluid is removed. They are generally taken out of the hipbone. These samples are sent to the laboratory for examination. In addition to diagnosis, the biopsy may also be repeated during the treatment phase of the disease to see if the lymphoma is responding to therapy.

Once the exact form of lymphoma is known, it is then staged to determine how aggressive it is, and how far it has spread. Staging is necessary to plan appropriate treatment.

Conventional imaging tests, such as x rays, computed tomography scans (CT scans ), magnetic resonance imaging (MRI), and abdominal sonograms,

are used to determine how far the disease has spread.

Rarely, a lumbar puncture or a spinal tap is performed to check if malignant cells are present in the fluid surrounding the brain. In this test, the physician inserts a needle into the epidural space at the base of the spine and collects a small amount of spinal fluid for microscopic examination.

Treatment

Much progress has been made in the treatment of non-Hodgkin's lymphoma. Treatment options for lymphomas depend on the type of lymphoma and its present stage. In most cases, treatment consists of chemotherapy , radiotherapy, or a combination of the two methods.

Chemotherapy is the use of anti-cancer drugs to kill cancer cells. In non-Hodgkin's lymphomas, combination therapy, which involves the use of multiple drugs, has been found more effective than single drug use. The treatment may last about six months, but in some cases may last as long as a year. The drugs may either be administered intravenously or given orally in the form of pills. If cancer cells have invaded the central nervous system, then chemotherapeutic drugs may be injected, through a needle in the brain or back, into the fluid that surrounds the brain. This procedure is known as intrathecal chemotherapy.

Radiation therapy, where high-energy ionizing rays are directed at specific portions of the body, such as the upper chest, abdomen, pelvis, or neck, is often used for treatment of lymphomas. External radiation therapy, where the rays are directed from a source outside the body, is the most common mode of radiation treatment.

Stem cell transplantation is used in cases where the lymphomas do not respond to conventional therapy, or in cases where the patient has had a relapse or suffers from recurrent lymphomas. However, one study done in the Netherlands suggested that patients may do just as well with a standard chemotherapy regimen rather than the transplant.

There are two ways of performing stem cell transplantation. In a procedure called “allogeneic stem cell transplant,” a donor is found whose cells match that of the patient. The donor can be a twin (best match), a sibling, or a person who is not related at all. High-dose chemotherapy or radiation therapy is given to eradicate the lymphoma. The donor stem cells are then given to replace those destroyed by the therapy.

In “autologous stem cell transplantation,” some of the patient's own stem cells are collected, “purged” of lymphoma cells, and frozen. High-dose chemotherapy and radiation therapy are given. The stem cells that were taken and frozen are then thawed and put back into the patient's body to replace the destroyed marrow. One of the serious risks of autologous stem cell transplants is that it is possible for some of the lymphoma cells to remain even after purging the stem cells.

There are no proven alternative treatments for non-Hodgkin's lymphoma. However, many complementary therapies, including vitamins and herbal remedies, massage, and acupuncture , may help persons going through treatment to better cope with the side effects they might experience. Because many of these therapies have not been studied thoroughly, it is not known which ones may be potentially harmful or helpful. Therefore, the patient with lymphoma should be advised to speak with their health care professional prior to trying any alternative or complementary treatment.

Prognosis

Like all cancers, the prognosis for lymphoma depends on the stage of the cancer, and the patient's age and general health. When all the different types and stages of lymphoma are considered together, only 50% of patients survive five years or more after initial diagnosis. This is because some types of lymphoma are more aggressive than others. Patients with T-cell lymphomas generally have a worse prognosis than those with B-cell types.

KEY TERMS

Antibodies —Proteins made by the B lymphocytes in response to the presence of infectious agents such as bacteria or viruses in the body.

Autoimmune disease —A disease caused by a person's own antibodies or T cells that attack molecules, cells, or tissues.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Growth factors (cytokines) —Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called “growth factors.”

Metastasize —The spread of a disease, such as a cancer, from its original site to another part of the body.

The five-year survival rate for those with non-Hodgkin's lymphoma rose from 31% in 1960 to 51% in 1994. The overall survival rate among children, 78%, is definitely better than among older people. About 90% of the children diagnosed with early stage disease survive five years or more, while only 60–70% of adults diagnosed with low grade lymphomas survive for five years or more.

Caregiver concerns

Many members of the health care team will work with the lymphoma patient. The primary physician may initially suspect lymphoma and order the appropriate diagnostic workup. The surgeon performs the biopsy, and the pathologist confirms the cellular diagnosis. Various x-ray and lab technicians will perform other imaging studies. Specially trained nurses administer chemotherapy and will instruct the patient on all aspects of his diagnosis and treatment. The patient may see both a medical and radiation oncologist, depending upon the specifics of the treatment ordered. Registered nurses also provide parttime family education.

Prevention

Although many cancers may be prevented by making diet and life style changes which reduce risk factors, there is currently no known way to prevent lymphomas. Protecting oneself from developing AIDS, which may be a risk factor for lymphomas, is the only preventive measure that can be practiced.

No special tests are available for early detection of non-Hodgkin's lymphomas. Paying prompt attention to the signs and symptoms of this disease and seeing a doctor if the symptoms persist are the best strategies for an early diagnosis of lymphoma. Early detection affords the best chance for a cure.

Resources

BOOKS

Beers, Mark H. and Robert Berkow, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck and Company, Inc., 1999.

PERIODICALS

“Bexxar Highly Effective First-Line Treatment.” Vaccine Weekly (June 7, 2000).

Gottlieb, Scott. “Bone Marrow Transplants Show No Benefit For Non-Hodgkin's Lymphoma.” British Medical Journal (January 20, 2001): 127.

ORGANIZATIONS

American Cancer Society. (800) ACS-2345. http://www.cancer.org.

The Leukemia and Lymphoma Society of America, Inc. 1311 Mamaroneck Ave, White Plains, NY 10605. (914) 949-5213. http://www.leukemia-lymphoma.org.

Lymphoma Research Foundation. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204-7040. http://www.lymphoma.org.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4CANCER. http://www.nci.nih.gov.

Deanna Swartout-Corbeil R.N.

Malignant Lymphomas

Definition

Malignant lymphomas are a group of cancers in which cells of the lymphatic system become abnormal and start to grow uncontrollably and spread (metastasize) throughout the body. Because lymph tissue is in many parts of the body, lymphomas can start in almost any organ of the body. Lymphomas are classified as being either non-Hodgkin's lymphoma or Hodgkin's disease.

Description

The lymph system is made up of ducts or tubules that carry lymph to all parts of the body. Lymph is a milky fluid that contains the lymphocytes or white blood cells, as well as protein and waste products. These are the infection-fighting cells of the blood. Small pea-shaped organs are found along the network of lymph vessels. These are called the lymph nodes, and their main function is to make and store lymphocytes. Clusters of lymph nodes are found in the pelvis region, underarm, neck, chest, and abdomen. The spleen, the tonsils, and the thymus are part of the lymphatic system.

The lymphocyte is the main cell of the lymphoid tissue. There are two main types of lymphocytes: the T lymphocyte and the B lymphocyte. Lymphomas develop from these two cell types. B cell lymphomas are more common among adults; while among children, the incidence of T and B cell lymphomas is almost equal.

The T and the B cell perform different jobs within the immune system. When an infectious bacterium enters the body, the B cell makes proteins called "antibodies." These antibodies attach themselves to the bacteria and flag them for destruction by other immune cells. The T cells help protect the body against viruses. When a virus enters the cell, it generally produces certain proteins that are projected on the surface of the infected cell. T cells recognize these proteins and produce certain substances (cytokines) that destroy the infected cells. Some of the cytokines made by the T cells attract other cell types, which are capable of digesting the virus-infected cell. The T cells can also destroy some types of cancerous cells.

Lymphomas can be divided into two main types: Hodgkin's lymphoma or Hodgkin's disease, and non-Hodgkin's lymphomas. The two are distinguished by cell type and have similar symptoms. Non-Hodgkin's lymphomas are more common, with at least 30 different types. Hodgkin's primarily affects individuals between 15-40 years of age, while Non-Hodgkin's occurs mainly in persons between the ages of 30-70.

Lymphomas are grouped (staged) by how aggressively they grow—slow growing (low grade, mostly found in B-cell types), intermediate growing (seen in both B-cell and T-cell types), and rapidly growing (high grade, seen in both B-cell and T-cell types)—and how far they spread. Lymphomas are also staged by the Roman numerals I, II, III, and IV. These stages indicate the following:

• Stage I. There is only one cancer site. No bone marrow involvement found.
• Stage II. Two sites are found, either above or below the diaphragm. There is no bone marrow involvement.
• Stage III. Sites are found above and below the diaphragm, but there is still no bone marrow involvement.

• Stage IV. The bone marrow is involved and the cancer cells have metastasized beyond the lymphatic system.

A majority of non-Hodgkin's lymphomas begin in the lymph nodes. About 20% start in other organs, such as the lungs, liver, or the gastrointestinal tract. Malignant lymphocytes multiply uncontrollably and do not perform their normal functions. Hence, the body's ability to fight infections is affected. In addition, these malignant cells may crowd the bone marrow and, depending on the stage, prevent the production of normal red blood cells, white blood cells, and platelets. A low red blood cell count causes anemia, while a reduction in the number of platelets makes the person susceptible to excessive bleeding. Cancerous cells can also invade other organs through the circulatory system of the lymph, causing those organs to malfunction.

In 2001, an estimated 56,200 Americans received a diagnosis of non-Hodgkin's lymphoma, and approximately 16,300 people died from malignant lymphomas. It is the fifth most common cancer in the country (not including nonmelanoma skin cancers). The incidence of non-Hodgkin's lymphoma has nearly doubled since the 1970s; however, during the 1990s the rate began to decline. The increase was related both to an actual increase in the number of cases as well as improved methods of detecting the disease. Over 95% of non-Hodgkin's lymphomas occur in adults, with the average age at diagnosis being in the early 40s. The disease more commonly occurs in men than women, and whites are affected to a greater extent than Asian Americans or African Americans.

Causes and symptoms

The exact cause of non-Hodgkin's lymphomas is not known. However, the incidence has increased significantly in recent years. Part of the increase is due to the AIDS epidemic. Individuals infected with the AIDS virus have a higher likelihood of developing non-Hodgkin's lymphomas.

People exposed to certain pesticides and ionizing radiation have a higher than average chance of developing this disease. For example, an increased incidence of lymphomas has been seen in survivors of the atomic bomb explosion in Hiroshima, and in people who have undergone aggressive radiation therapy. People who suffer from immune-deficient (immunodeficiency ) disorders and those who have been treated with immune suppressive drugs for transplants or for conditions such as rheumatoid arthritis and autoimmune diseases are at an increased risk for this disease.

Some studies have shown a loose association between retroviruses, such as HTLV-I, and some rare forms of lymphoma. The Epstein-Barr virus has been linked to Burkitt's lymphoma in African countries. However, a direct cause-and-effect relationship has not been established.

The symptoms of lymphomas are often vague and non-specific. The signs and symptoms may differ, depending on the location of the involvement. Patients may experience loss of appetite, weight loss, nausea, vomiting, abdominal discomfort, and indigestion. The patient may complain of a feeling of fullness, which is a result of enlarged lymph nodes in the abdomen. Sometimes the abdomen can become so swollen it may resemble pregnancy in a woman. Pressure or pain in the lower back is another symptom. In the advanced stages, the patient may have bone pain, headaches, constant coughing, and abnormal pressure and congestion in the face, neck, and upper chest. Some may have fevers and night sweats. In most cases, patients go to the doctor because of the presence of swollen glands in the neck, armpits, or groin area. Since all the symptoms are common to many other illnesses, it is essential to seek medical attention if any of the conditions persist for two weeks or more. Only a qualified physician can correctly diagnose whether the symptoms are due to lymphoma or some other ailment.

Diagnosis

Like all cancers, lymphomas are best treated when found early. However, it is often difficult to diagnose lymphomas. There are no screening tests available; and, since the symptoms are non-specific, lymphomas are rarely recognized in their early stages. Detection often occurs by chance during a routine physical examination.

When the doctor suspects lymphoma, a complete medical history is taken and a thorough physical examination is performed. Enlargement of the lymph nodes, liver, or spleen may suggest lymphomas. Blood tests will determine the cell counts and obtain information on how well the organs, such as the kidney and liver, are functioning.

A biopsy of the enlarged lymph node is the most definitive diagnostic tool for staging purposes. The doctor may perform a bone marrow biopsy. During the biopsy, a cylindrical piece of bone and marrow fluid is removed. They are generally taken out of the hipbone. These samples are sent to the laboratory for examination. In addition to diagnosis, the biopsy may also be repeated during the treatment phase of the disease to see if the lymphoma is responding to therapy.

Once the exact form of lymphoma is known, it is then staged to determine how aggressive it is, and how far it has spread. Staging is necessary to plan appropriate treatment.

Conventional imaging tests, such as x rays, computed tomography scans (CT scans), magnetic resonance imaging (MRI), and abdominal sonograms, are used to determine how far the disease has spread.

Rarely, a lumbar puncture or a spinal tap is performed to check if malignant cells are present in the fluid surrounding the brain. In this test, the physician inserts a needle into the epidural space at the base of the spine and collects a small amount of spinal fluid for microscopic examination.

Treatment

Much progress has been made in the treatment of non-Hodgkin's lymphoma. Treatment options for lymphomas depend on the type of lymphoma and its present stage. In most cases, treatment consists of chemotherapy, radiotherapy, or a combination of the two methods.

Chemotherapy is the use of anti-cancer drugs to kill cancer cells. In non-Hodgkin's lymphomas, combination therapy, which involves the use of multiple drugs, has been found more effective than single drug use. The treatment may last about six months, but in some cases may last as long as a year. The drugs may either be administered intravenously or given orally in the form of pills. If cancer cells have invaded the central nervous system, then chemotherapeutic drugs may be injected, through a needle in the brain or back, into the fluid that surrounds the brain. This procedure is known as intrathecal chemotherapy.

Radiation therapy, where high-energy ionizing rays are directed at specific portions of the body, such as the upper chest, abdomen, pelvis, or neck, is often used for treatment of lymphomas. External radiation therapy, where the rays are directed from a source outside the body, is the most common mode of radiation treatment.

Stem cell transplantation is used in cases where the lymphomas do not respond to conventional therapy, or in cases where the patient has had a relapse or suffers from recurrent lymphomas. However, one study done in the Netherlands suggested that patients may do just as well with a standard chemotherapy regimen rather than the transplant.

There are two ways of performing stem cell transplantation. In a procedure called "allogeneic stem cell transplant," a donor is found whose cells match that of the patient. The donor can be a twin (best match), a sibling, or a person who is not related at all. High-dose chemotherapy or radiation therapy is given to eradicate the lymphoma. The donor stem cells are then given to replace those destroyed by the therapy.

In "autologous stem cell transplantation," some of the patient's own stem cells are collected, "purged" of lymphoma cells, and frozen. High-dose chemotherapy and radiation therapy are given. The stem cells that were taken and frozen are then thawed and put back into the patient's body to replace the destroyed marrow. One of the serious risks of autologous stem cell transplants is that it is possible for some of the lymphoma cells to remain even after purging the stem cells.

There are no proven alternative treatments for non-Hodgkin's lymphoma. However, many complementary therapies, including vitamins and herbal remedies, massage, and acupuncture, may help persons going through treatment to better cope with the side effects they might experience. Because many of these therapies have not been studied thoroughly, it is not known which ones may be potentially harmful or helpful. Therefore, the patient with lymphoma should be advised to speak with their health care professional prior to trying any alternative or complementary treatment.

Prognosis

Like all cancers, the prognosis for lymphoma depends on the stage of the cancer, and the patient's age and general health. When all the different types and stages of lymphoma are considered together, only 50% of patients survive five years or more after initial diagnosis. This is because some types of lymphoma are more aggressive than others. Patients with T-cell lymphomas generally have a worse prognosis than those with B-cell types.

The five-year survival rate for those with non-Hodgkin's lymphoma rose from 31% in 1960 to 51% in 1994. The overall survival rate among children, 78%, is definitely better than among older people. About 90% of the children diagnosed with early stage disease survive five years or more, while only 60-70% of adults diagnosed with low grade lymphomas survive for five years or more.

Health care team roles

Many members of the health care team will work with the lymphoma patient. The primary physician may initially suspect lymphoma and order the appropriate diagnostic workup. The surgeon performs the biopsy, and the pathologist confirms the cellular diagnosis. Various x-ray and lab technicians will perform other imaging studies. Specially trained nurses administer chemotherapy and will instruct the patient on all aspects of his diagnosis and treatment. The patient may see both a medical and radiation oncologist, depending upon the specifics of the treatment ordered. Registered nurses also provide part-time family education.

Prevention

Although many cancers may be prevented by making diet and life style changes which reduce risk factors, there is currently no known way to prevent lymphomas. Protecting oneself from developing AIDS, which may be a risk factor for lymphomas, is the only preventive measure that can be practiced.

No special tests are available for early detection of non-Hodgkin's lymphomas. Paying prompt attention to the signs and symptoms of this disease and seeing a doctor if the symptoms persist are the best strategies for an early diagnosis of lymphoma. Early detection affords the best chance for a cure.

KEY TERMS

Antibodies— Proteins made by the B lymphocytes in response to the presence of infectious agents such as bacteria or viruses in the body.

Autoimmune disease— A disease caused by a per son's own antibodies or T cells that attack molecules, cells, or tissues.

Biopsy— The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Growth factors (cytokines)— Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors."

Metastasize— The spread of a disease, such as a cancer, from its original site to another part of the body.

Resources

BOOKS

Beers, Mark H. and Robert Berkow, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck and Company, Inc., 1999.

PERIODICALS

"Bexxar Highly Effective First-Line Treatment." Vaccine Weekly (June 7, 2000).

Gottlieb, Scott. "Bone Marrow Transplants Show No Benefit For Non-Hodgkin's Lymphoma." British Medical Journal (January 20, 2001): 127.

ORGANIZATIONS

American Cancer Society. (800) ACS-2345. 〈http://www.cancer.org〉.

The Leukemia and Lymphoma Society of America, Inc. 1311 Mamaroneck Ave, White Plains, NY 10605. (914) 949-5213. 〈http://www.leukemialymphoma.org〉.

Lymphoma Research Foundation. 8800 Venice Boulevard, Suite 207, Los Angeles, CA 90034. (310) 204-7040. 〈http://www.lymphoma.org〉.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4CANCER. 〈http://www.nci.nih.gov〉.