Chronic Lymphocytic Leukemia Treatment (PDQ®)

• General Information About Chronic Lymphocytic Leukemia
• Stages of Chronic Lymphocytic Leukemia
• Refractory Chronic Lymphocytic Leukemia
• Treatment Option Overview
• Treatment Options by Stage
• Stage 0 Chronic Lymphocytic Leukemia
• Stage I, Stage II, Stage III, and Stage IV Chronic Lymphocytic Leukemia
• Treatment Options for Refractory Chronic Lymphocytic Leukemia
• To Learn More About Chronic Lymphocytic Leukemia
• Changes to This Summary (10/03/2008)

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).
• Older age can affect the risk of developing chronic lymphocytic leukemia.
• Possible signs of chronic lymphocytic leukemia include swollen lymph nodes and tiredness.
• Tests that examine the blood, bone marrow, and lymph nodes are used to detect (find) and diagnose chronic lymphocytic leukemia.
• Certain factors affect treatment options and prognosis (chance of recovery).

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 the second most common type of leukemia in adults. It often occurs during or after middle age; it rarely occurs in children.

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

The myeloid stem cell develops into one of three types of mature blood cells:

• Red blood cells that carry oxygen and other materials to all tissues of the body.
• White blood cells that fight infection and disease.
• Platelets that help prevent bleeding by causing blood clots to form.

The lymphoid stem cell develops into a lymphoblast cell and then into one of three types of lymphocytes (white blood cells):

• B lymphocytes that make antibodies to help fight infection.
• T lymphocytes that help B lymphocytes make antibodies to fight infection.
• Natural killer cells that attack cancer cells and viruses.

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.

In CLL, too many blood stem cells develop into abnormal lymphocytes and do not become healthy white blood cells. The abnormal lymphocytes may also be called leukemic 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 result in infection, anemia, and easy bleeding.

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

• Adult Acute Lymphoblastic Leukemia Treatment.
• Childhood Acute Lymphoblastic Leukemia Treatment.
• Adult Acute Myeloid Leukemia Treatment.
• Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment.
• Chronic Myelogenous Leukemia Treatment.
• Hairy Cell Leukemia Treatment.

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. People who think they may be at risk should discuss this with their doctor. 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.

Possible signs of chronic lymphocytic leukemia include swollen lymph nodes and tiredness.

Usually CLL does not cause any symptoms and is found during a routine blood test. Sometimes symptoms occur that may be caused by CLL or by other conditions. A doctor should be consulted if any of the following problems occur:

• 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): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • 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.

  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.

• Cytogenetic analysis: A test in which cells in a sample of blood or bone marrow are viewed under a microscope to look for changes in the structure or number of chromosomes in the lymphocytes.
• Immunophenotyping: A test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if malignant lymphocytes (cancer) began from the B lymphocytes or the T lymphocytes.
• 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.

  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.

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 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.
• There are three ways that cancer spreads in the body.
• The following stages are used for chronic lymphocytic leukemia:
• Stage 0
• Stage I
• Stage II
• Stage III
• Stage IV

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:

• 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.
• 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 Coomb's test.

There are three ways that cancer spreads in the body.

When cancer cells spread outside the blood, a solid tumor may form. This process is called metastasis. The three ways that cancer cells spread in the body are:

• Through the blood. Cancer cells travel through the blood, invade solid tissues in the body, such as the brain or heart, and form a solid tumor.
• Through the lymph system. Cancer cells invade the lymph system, travel through the lymph vessels, and form a solid tumor in other parts of the body.
• Through solid tissue. Cancer cells that have formed a solid tumor spread to tissues in the surrounding area.

The new (metastatic) tumor is the same type of cancer as the primary cancer. For example, if leukemia cells spread to the brain, the cancer cells in the brain are actually leukemia cells. The disease is metastatic leukemia, not brain cancer.

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 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

Refractorychronic 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.
• Five types of standard treatment are used:
• Watchful waiting
• Radiation therapy
• Chemotherapy
• Surgery
• Monoclonal antibody therapy
• New types of treatment are being tested in clinical trials.
• Chemotherapy with stem cell transplant
• Patients may want to think about taking part in a clinical trial.
• Patients can enter clinical trials before, during, or after starting their cancer treatment.
• Follow-up tests may be needed.

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 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 spinal column, 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.

Surgery

Splenectomy is surgery to remove the spleen.

Monoclonal antibody therapy

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.

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.

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 clinical trials database.

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

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

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 PDQ Cancer Clinical Trials Registry 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. 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:

• Watchful waiting when there are few or no symptoms.
• Monoclonal antibody therapy.
• Chemotherapy with 1 or more drugs, with or without steroids or monoclonal antibody therapy.
• Low-doseexternal radiation therapy to areas of the body where cancer is found, such as the spleen or lymph nodes.
• A clinical trial of chemotherapy and biologic therapy with stem cell transplant.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.

Treatment Options for Refractory Chronic Lymphocytic Leukemia

Treatment of refractorychronic lymphocytic leukemia may include the following:

• A clinical trial of chemotherapy with stem cell transplant.
• A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.

To Learn More About Chronic Lymphocytic Leukemia

For more information from the National Cancer Institute about chronic lymphocytic leukemia, see the following:

• Leukemia Home Page
• What You Need to Know About™ Leukemia
• Biological Therapies for Cancer: Questions and Answers

For general cancer information and other resources from the National Cancer Institute, see the following:

• What You Need to Know About™ Cancer - An Overview
• Understanding Cancer Series: Cancer
• Staging: Questions and Answers
• Chemotherapy and You: Support for People With Cancer
• Radiation Therapy and You: Support for People With Cancer
• Coping with Cancer
• Support and Resources
• Cancer Library
• Information For Survivors/Caregivers/Advocates

Changes to This Summary (10/03/2008)

The PDQcancer 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.

Changes were made to this summary to match those made to the health professional version.