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Chronic Lymphocytic Leukemia Treatment (PDQ®)

Patient Version
Last Modified: 11/11/2014

General Information About Chronic Lymphocytic Leukemia



Chronic lymphocytic leukemia is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).

Chronic lymphocytic leukemia (also called CLL) is a blood and bone marrow disease that usually gets worse slowly. CLL is one of the most common types of leukemia in adults. It often occurs during or after middle age; it rarely occurs in children.

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Anatomy of the bone; drawing shows spongy bone, red marrow, and yellow marrow. A cross section of the bone shows compact bone and blood vessels in the bone marrow. Also shown are red blood cells, white blood cells, platelets, and a blood stem cell.
Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone makes up the outer layer of the bone. Spongy bone is found mostly at the ends of bones and contains red marrow. Bone marrow is found in the center of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow marrow is made mostly of fat.

Leukemia may affect red blood cells, white blood cells, and platelets.

Normally, the body makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.

A myeloid stem cell becomes one of three types of mature blood cells:

A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):

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Blood cell development; drawing shows the steps a blood stem cell goes through to become a red blood cell, platelet, or white blood cell. A myeloid stem cell becomes a red blood cell, a platelet, or a myeloblast, which then becomes a granulocyte (the types of granulocytes are eosinophils, basophils, and neutrophils). A lymphoid stem cell becomes a lymphoblast and then becomes a B-lymphocyte, T-lymphocyte, or natural killer cell.
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

In CLL, too many blood stem cells become abnormal lymphocytes and do not become healthy white blood cells. The abnormal lymphocytes may also be called leukemia cells. The lymphocytes are not able to fight infection very well. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may cause infection, anemia, and easy bleeding.

This summary is about chronic lymphocytic leukemia. See the following PDQ summaries for more information about leukemia:

Older age can affect the risk of developing chronic lymphocytic leukemia.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for CLL include the following:

  • Being middle-aged or older, male, or white.
  • A family history of CLL or cancer of the lymph system.
  • Having relatives who are Russian Jews or Eastern European Jews.

Signs and symptoms of chronic lymphocytic leukemia include swollen lymph nodes and tiredness.

Usually CLL does not cause any signs or symptoms and is found during a routine blood test. Signs and symptoms may be caused by CLL or by other conditions. Check with your doctor if you have any of the following:

  • Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin.
  • Feeling very tired.
  • Pain or fullness below the ribs.
  • Fever and infection.
  • Weight loss for no known reason.

Tests that examine the blood, bone marrow, and lymph nodes are used to detect (find) and diagnose chronic lymphocytic leukemia.

The following tests and procedures may be used:

  • Physical exam and history : An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

  • Complete blood count (CBC) with differential : A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells and platelets.
    • The number and type of white blood cells.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the blood sample made up of red blood cells.
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    Complete blood count (CBC); left panel shows blood being drawn from a vein on the inside of the elbow using a tube attached to a syringe; right panel shows a laboratory test tube with blood cells separated into layers: plasma, white blood cells, platelets, and red blood cells.
    Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.

  • Immunophenotyping : A laboratory test in which the antigens or markers on the surface of a blood or bone marrow cell are checked to see if they are lymphocytes or myeloid cells. If the cells are malignant lymphocytes (cancer), they are checked to see if they are B lymphocytes or T lymphocytes.

  • FISH (fluorescence in situ hybridization): A laboratory technique used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light.

  • Flow cytometry : A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light.

  • IgVH gene mutation test: A laboratory test done on a bone marrow or blood sample to check for an IgVH gene mutation. Patients with an IgVH gene mutation have a better prognosis.

  • Bone marrow aspiration and biopsy : The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.
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    Bone marrow aspiration and biopsy; drawing shows a patient lying face down on a table and a Jamshidi needle (a long, hollow needle) being inserted into the hip bone. Inset shows the Jamshidi needle being inserted through the skin into the bone marrow of the hip bone.
    Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.

Certain factors affect treatment options and prognosis (chance of recovery).

Treatment options depend on:

  • The stage of the disease.
  • Red blood cell, white blood cell, and platelet blood counts.
  • Whether there are signs or symptoms, such as fever, chills, or weight loss.
  • Whether the liver, spleen, or lymph nodes are larger than normal.
  • The response to initial treatment.
  • Whether the CLL has recurred (come back).

The prognosis (chance of recovery) depends on:

  • Whether there is a change in the DNA and the type of change, if there is one.
  • Whether lymphocytes are spread throughout the bone marrow.
  • The stage of the disease.
  • Whether the CLL gets better with treatment or has recurred (come back).
  • Whether the CLL progresses to lymphoma or prolymphocytic leukemia.
  • The patient's general health.

Stages of Chronic Lymphocytic Leukemia



After chronic lymphocytic leukemia has been diagnosed, tests are done to find out how far the cancer has spread in the blood and bone marrow.

Staging is the process used to find out how far the cancer has spread. It is important to know the stage of the disease in order to plan the best treatment. The following tests may be used in the staging process:

  • Chest x-ray : An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body, such as the lymph nodes.

  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain and spinal cord. This procedure is also called nuclear magnetic resonance imaging (NMRI).

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

  • Blood chemistry studies : A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

  • Antiglobulin test : A test in which a sample of blood is looked at under a microscope to find out if there are any antibodies on the surface of red blood cells or platelets. These antibodies may react with and destroy the red blood cells and platelets. This test is also called a Coombs test.

The following stages are used for chronic lymphocytic leukemia:

Stage 0

In stage 0 chronic lymphocytic leukemia, there are too many lymphocytes in the blood, but there are no other signs or symptoms of leukemia. Stage 0 chronic lymphocytic leukemia is indolent (slow-growing).

Stage I

In stage I chronic lymphocytic leukemia, there are too many lymphocytes in the blood and the lymph nodes are larger than normal.

Stage II

In stage II chronic lymphocytic leukemia, there are too many lymphocytes in the blood, the liver or spleen is larger than normal, and the lymph nodes may be larger than normal.

Stage III

In stage III chronic lymphocytic leukemia, there are too many lymphocytes in the blood and there are too few red blood cells. The lymph nodes, liver, or spleen may be larger than normal.

Stage IV

In stage IV chronic lymphocytic leukemia, there are too many lymphocytes in the blood and too few platelets. The lymph nodes, liver, or spleen may be larger than normal and there may be too few red blood cells.

Refractory Chronic Lymphocytic Leukemia

Refractory chronic lymphocytic leukemia is cancer that does not get better with treatment.

Treatment Option Overview



There are different types of treatment for patients with chronic lymphocytic leukemia.

Different types of treatment are available for patients with chronic lymphocytic leukemia. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change. This is also called observation. During this time, problems caused by the disease, such as infection, are treated.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, or the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Chronic Lymphocytic Leukemia for more information.

Surgery

Splenectomy is surgery to remove the spleen.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy and tyrosine kinase inhibitor therapy are types of targeted therapy used in the treatment of chronic lymphocytic leukemia.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances in the body that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

Tyrosine kinase inhibitor therapy is a cancer treatment that blocks signals needed for tumors to grow.

See Drugs Approved for Chronic Lymphocytic Leukemia for more information.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Chemotherapy with stem cell transplant

Chemotherapy with stem cell transplant is a method of giving chemotherapy and replacing blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage



Stage 0 Chronic Lymphocytic Leukemia

Treatment of stage 0 chronic lymphocytic leukemia is usually watchful waiting.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage I, Stage II, Stage III, and Stage IV Chronic Lymphocytic Leukemia

Treatment of stage I, stage II, stage III, and stage IV chronic lymphocytic leukemia may include the following:

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia and stage IV chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Refractory Chronic Lymphocytic Leukemia

Treatment of refractory chronic lymphocytic leukemia may include the following:

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with refractory chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Changes to This Summary (11/11/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

About This PDQ Summary



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This PDQ cancer information summary has current information about the treatment of chronic lymphocytic leukemia. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

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Clinical Trial Information

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Clinical trials are listed in PDQ and can be found online at NCI's Web site. Many cancer doctors who take part in clinical trials are also listed in PDQ. For more information, call the Cancer Information Service 1-800-4-CANCER (1-800-422-6237).

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