Chronic lymphocytic leukemia

What is chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) is a disease in which too many lymphocytes are found in the body. Lymphocytes are infection-fighting white blood cells. They are made in the bone marrow and by other organs of the lymph system. The bone marrow is the spongy tissue inside the large bones in the body. The bone marrow makes:

• Red blood cells (which carry oxygen and other materials to all tissues of the body)
• White blood cells (which fight infection)
• Platelets (which make the blood clot)

Normally, bone marrow cells called blasts develop (mature) into several different types of blood cells. These cells have specific jobs to do in the body.

The lymph system

The lymph system is made up of thin tubes that branch, like blood vessels, into all parts of the body. Lymph vessels carry lymph, a colorless, watery fluid that contains l ymphocytes . Along the network of vessels are groups of small, bean-shaped organs called lymph nodes . Clusters of lymph nodes are found in the underarm, pelvis, neck, and abdomen. The spleen (an organ in the upper abdomen that makes lymphocytes and filters old blood cells from the blood), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat) are also part of the lymph system.

Lymphocytes fight infection by making substances called antibodies . Antibodies attack germs and other harmful things in the body. In CLL, the developing lymphocytes do not mature correctly and too many are made. The lymphocytes may look normal, but they cannot fight infection as well as they should. These immature lymphocytes are then found in the blood and the bone marrow. They also collect in the lymph tissues and make them swell. Lymphocytes may crowd out other blood cells in the blood and bone marrow. Anemia may develop if the bone marrow cannot make enough red blood cells to carry oxygen. If the bone marrow cannot make enough platelets to make the blood clot normally, bleeding or bruising may occur easily.

Symptoms and diagnosis

Leukemia can be acute (progressing quickly with many immature cells) or chronic (progressing slowly with more mature, normal-looking cells). Chronic lymphocytic leukemia progresses slowly. It usually occurs in people 60 years of age or older. In the first stages of the disease there are often no symptoms. As time goes on, more and more lymphocytes are made and symptoms begin to appear. A doctor should be seen if:

• The lymph nodes swell
• The spleen or liver becomes larger than normal
• A feeling of fatigue persists
• Bleeding occurs easily

If there are symptoms, a doctor will do a physical examination. He or she may order blood tests to count the number of each of the different kinds of blood cells. More blood tests may be done if the results of the blood tests are not normal.

The doctor also may do a bone marrow biopsy . During this test, a needle is inserted into a bone and a small amount of bone marrow is taken out. The marrow is looked at under the microscope. The doctor can then tell what kind of leukemia the patient has and plan the best treatment. The chance of recovery (prognosis) depends on the stage of the disease, and the patient's age and general health.

Stages of chronic lymphocytic leukemia

Once chronic lymphocytic leukemia has been found (diagnosed), more tests may be done. These tests are used to find out if leukemia cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease to plan treatment. The following stages are used for chronic lymphocytic leukemia:

• Stage 0
  There are too many lymphocytes in the blood, but there are usually no other symptoms of leukemia. Lymph nodes and the spleen and liver are not swollen. The number of red blood cells and platelets is normal.
• Stage I
  There are too many lymphocytes in the blood and lymph nodes are swollen. The spleen and liver are not swollen and the number of blood cells and platelets is normal.
• Stage II
  There are too many lymphocytes in the blood. Lymph nodes and the liver and spleen are swollen.
• Stage III
  There are too many lymphocytes in the blood and there are too few red blood cells (anemia). Lymph nodes and the liver or spleen may be swollen.
• Stage IV
  There are too many lymphocytes in the blood and too few platelets. This makes it hard for the blood to clot. The lymph nodes, liver, or spleen may be swollen and there may be too few red blood cells (anemia).
• Refractory
  Refractory means that the leukemia does not respond to treatment.

Treatment of chronic lymphocytic leukemia

There are treatments for all patients with chronic lymphocytic leukemia. Three kinds of treatment are used:

• Chemotherapy (using drugs to kill cancer cells)
• Radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)
• Treatment for complications of the leukemia, such as infection

The use of biological therapy (using the body's immune system to fight cancer) is being tested in clinical trials. Surgery may be used in certain cases.

Chemotherapy

Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by pill, or it may be put into the body by a needle in the vein or muscle. Chemotherapy is called a systemic treatment because the drug enters the bloodstream. From the bloodstream the drug travels through the body, and can kill cancer cells throughout the body.

Radiation

Radiation therapy uses x-rays or other high-energy rays to kill cancer cells and shrink tumors. Radiation for CLL usually comes from a machine outside the body (external radiation therapy). If the spleen is swollen, a doctor may take out the spleen in an operation called a splenectomy . This is only done in rare cases.

Biological therapy

Biological therapy tries to get the body to fight cancer. It uses materials made by the body or made in a laboratory. Biological therapy is used to boost, direct, or restore the body's natural defenses against disease. Biological therapy is sometimes called biological response modifier (BRM) therapy or immunotherapy.

Infection often occurs in patients with CLL. A special substance called immunoglobulin may be given to prevent infections. Sometimes a special machine is used to filter the blood to take out extra lymphocytes. This is called leukapheresis .

Bone marrow transplantation

Bone marrow transplantation is used to replace the bone marrow with healthy bone marrow. First, all of the bone marrow in the body is destroyed with high doses of chemotherapy with or without radiation therapy. Healthy marrow is then taken from another person (a donor) whose tissue is the same as or almost the same as the patient's. The donor may be a twin (the best match), a brother or sister, or another person not related. The healthy marrow from the donor is given to the patient through a needle in the vein. The marrow replaces the marrow that was destroyed. A bone marrow transplant using marrow from a relative or person not related to the patient is called an allogeneic bone marrow transplant .

Another type of bone marrow transplant, called autologous bone marrow transplant , is being studied in clinical trials. To do this type of transplant, bone marrow is taken from the patient and treated with drugs to kill any cancer cells. The marrow is frozen to save it. Next, the patient is given high-dose chemotherapy with or without radiation therapy. This destroys all of the remaining marrow. The frozen marrow that was saved is then thawed and given back to the patient through a needle in a vein. This replaces the marrow that was destroyed.

Treatment by stage

Treatment of chronic lymphocytic leukemia depends on the stage of the disease, and the patient's age and overall health. Most patients with chronic lymphocytic leukemia are not cured with standard therapy. Some standard treatments may have more side effects than are desired. For these reasons, clinical trials are designed to find better ways to treat cancer patients. They are based on the most up-to-date information. Clinical trials are on going in most parts of the country for most stages of chronic lymphocytic leukemia. To know more about clinical trials, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237); TTY at 1-800-332-8615.

Stage 0

If the patient has stage 0 CLL, treatment may not be needed or chemotherapy may be given. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.

Stage I

Treatment may be one of the following:

1. If there are no symptoms, no treatment may be needed. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.
2. Chemotherapy with or without steroids
3. Other chemotherapy drugs
4. External radiation therapy to swollen lymph nodes
5. Combination chemotherapy
6. A clinical trial evaluating monoclonal antibodies
7. A clinical trial evaluating bone marrow or peripheral stem cell transplantation

Stage II

Treatment may be one of the following:

1. If there are few or no symptoms, no treatment may be needed. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.
2. Chemotherapy with or without steroids
3. Other chemotherapy drugs
4. Combination chemotherapy
5. External radiation therapy to swollen lymph nodes
6. External radiation therapy to the spleen to reduce symptoms caused by the enlargement of the spleen
7. A clinical trial evaluating monoclonal antibodies
8. A clinical trial evaluating bone marrow or peripheral stem cell transplantation

Stage III

Treatment may be one of the following:

1. If there are few or no symptoms, no treatment may be needed. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.
2. Chemotherapy with or without steroids
3. Other chemotherapy drugs
4. Combination chemotherapy
5. Surgery to remove the spleen or external radiation therapy to the spleen to reduce symptoms caused by the enlargement of the spleen
6. A clinical trial evaluating monoclonal antibodies
7. A clinical trial evaluating bone marrow or peripheral stem cell transplantation

Stage IV

Treatment may be one of the following:

1. If there are few or no symptoms, no treatment may be needed. A doctor will follow the patient closely so treatment can be started if the leukemia gets worse.
2. Chemotherapy with or without steroids
3. Other chemotherapy drugs
4. Combination chemotherapy
5. Surgery to remove the spleen or external radiation therapy to the spleen to reduce symptoms caused by the enlargement of the spleen
6. A clinical trial evaluating monoclonal antibodies
7. A clinical trial evaluating bone marrow or peripheral stem cell transplantation

Refractory

Treatment depends on many factors. Patients may wish to consider entering a clinical trial. Clinical trials use new chemotherapy drugs and bone marrow or peripheral stem cell transplantation.