Chronic lymphocytic leukemia

Facts

Chronic lymphocytic leukemia (CLL) is one type of cancer of the bone marrow and blood. It is also called chronic lymphoid leukemia or small lymphocytic lymphoma.

Seattle Cancer Care Alliance (SCCA) offers comprehensive treatment from a team of experts for all types of leukemia and lymphoid malignancies, including CLL.

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Lymphoma Cancer that begins in the cells of the immune system. There are two basic categories of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas. Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

What is chronic lymphocytic leukemia?

In people with CLL, a type of blood cell called a lymphocyte begins to function abnormally. 

Most cases of CLL (about 95 percent) start in B lymphocytes (B-cells). 

  • The affected lymphocytes mature partially, but they never fully mature. 
  • These leukemic cells can carry out some, but not all, of their normal infection-fighting functions.
  • They build up in your bone marrow and blood, crowding out normal, healthy blood cells that your body needs. 
  • Low levels of normal blood cells can lead to infection, anemia and excessive bleeding. 
  • The leukemic cells can travel around your body through your bloodstream and interfere with the function of your organs.
  • Rarely, CLL transforms into another cancer, such as aggressive lymphoma

Other cancers that arise from lymphocytes

In addition to CLL, some rare types of leukemia and lymphoma arise from lymphocytes. SCCA experts treat all types, including these:

  • Prolymphocytic leukemia (PLL) — PLL tends to be more aggressive than most types of CLL. It can form in B-cells or T-cells, and it generally develops more quickly than CLL but not as fast as acute lymphoblastic leukemia.
  • Large granular lymphocytic (LGL) leukemia — LGL leukemia tends to be slow growing, but some cases are more aggressive. It is characterized by enlarged lymphocytes with visible granules, and it can form in T-cells or natural killer (NK) cells.
  • Hairy cell leukemia (HCL) — This slow-growing type is a cancer of the B-cells, but it is different from CLL. It gets its name from fine projections on the surface of the cells that make them look hairy.
  • Small lymphocytic lymphoma (SLL) — This disease is closely related to CLL. But in SLL, cancer cells are found in the lymph nodes and spleen, rather than the bone marrow and blood. Approximately 5,000 new cases of SLL are diagnosed annually in the United States. Most of the information in our web section about CLL also applies to SLL. 
Anemia A condition in which the number of red blood cells is below normal. B cell A type of white blood cell that makes antibodies. B cells are part of the immune system and develop from stem cells in the bone marrow. Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Lymphocyte A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes (white blood cells) are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. Lymphocyte A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes (white blood cells) are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. Lymphoma Cancer that begins in the cells of the immune system. There are two basic categories of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas. Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer. Spleen An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells and destroys old blood cells. It is on the left side of the abdomen near the stomach.

Understanding your bone marrow and blood

To understand leukemia, it helps to know the basics about your bone marrow and blood cells.

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets.
What are stem cells?

Stem cells are cells in your body that have the potential to turn into any kind of cell, such as a skin cell, liver cell, brain cell or blood cell. Stem cells that turn into blood cells are called hematopoietic stem cells, or blood stem cells. 

Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
Why are blood stem cells important?

When blood cells become old or damaged, they die, and blood stem cells produce new blood cells to replace them. Blood stem cells are mainly found in bone marrow (the soft, spongy tissue inside your bones), but some are also found in circulating blood.

Blood stem cells produce lymphoid stem cells and myeloid stem cells. 

  • Lymphoid stem cells produce lymphoblasts, which in turn produce several types of white blood cells, including lymphocytes and NK cells
  • Myeloid stem cells produce myeloblasts, which in turn produce white blood cells known as granulocytes, as well as red blood cells and platelets.
Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Lymphocyte A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes (white blood cells) are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. Natural killer cell A type of immune cell that has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus. A natural killer cell is a type of white blood cell. Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Red blood cell A type of blood cell that carries oxygen in the body. Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
What do healthy blood cells do?

Healthy white blood cells, red blood cells and platelets are essential.

  • White blood cells fight infection. The main types of white blood cells are B-cells, T-cells, NK cells and granulocytes.
  • Red blood cells carry oxygen from your lungs to other parts of your body and take carbon dioxide back to your lungs to be removed.
  • Platelets make your blood clot and slow or stop bleeding. 

Bloodcells

Natural killer cell A type of immune cell that has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus. A natural killer cell is a type of white blood cell. Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Red blood cell A type of blood cell that carries oxygen in the body.

Symptoms

In the early stages, CLL usually doesn’t cause symptoms, and it may take years before symptoms develop. Once they do, CLL is often treated as a chronic disease.

Symptoms of CLL are often similar to the flu or other common, less serious diseases. Check with your doctor if you have any of these. 

Symptoms from low white blood cells:

  • Flu-like symptoms, such as fever, sweats, and body aches
  • Infections 

Symptoms from low red blood cells:

  • Shortness of breath
  • Fatigue, weakness, lack of energy, or sleepiness

Symptoms from low platelets:

  • Bleeding from your gums
  • Red spots on your palate or ankles
  • Easy bruising or prolonged bleeding from cuts
  • Frequent or severe nosebleeds

Other general symptoms:

  • Loss of appetite
  • Unexplained weight loss
  • Pain or aches in your bones or joints
  • Swollen abdomen
  • Swollen lymph nodes in your neck, underarm, stomach or groin.
Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Red blood cell A type of blood cell that carries oxygen in the body. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Diagnosing

If your doctor suspects you may have leukemia, they will want to perform a thorough physical examination and talk with you about your medical history.

An accurate diagnosis of CLL requires several tests. You might have any of these (but you may not need all of them) to confirm that you have CLL or to identify specific characteristics of your disease that can affect treatment decisions or help doctors predict the course your disease might take.

  • Blood tests — to check the types and numbers of blood cells and whether the lymphocytes appear abnormal (complete blood count and peripheral blood smear) and to see if leukemic cells are present, which type they are and whether there are signs of slow-growing or more aggressive CLL (immunophenotyping, or flow cytometry). Sometimes CLL is discovered during a routine blood test. 
  • Bone marrow tests — taking samples of bone marrow and a small piece of bone from your pelvis using a needle (bone marrow aspiration and biopsy) and checking them for leukemic cells. 
  • Chromosome tests — checking your blood or bone marrow cells for changes in chromosomes, such as missing parts of chromosomes, an extra copy of a chromosome or two chromosomes that have exchanged some DNA, or checking for changes in your immune system proteins that may predict how aggressive your CLL is. These tests include cytogenetic analysis, fluorescent in situ hybridization and polymerase chain reaction.
  • Imaging tests — such as chest X-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, or ultrasound to check whether leukemia is impacting other parts of your body.
Biopsy The removal of a sample of tissue or fluid that is examined to see whether cancer is present. This may be done with a large needle or through surgical removal of tissue or fluids. Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Chest X-ray A type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease. An X-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease. Chromosome Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. Chromosome Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. Computed tomography A procedure that uses a computer linked to an X-ray machine to make a series of detailed pictures of areas inside the body. The pictures are used to create three-dimensional (3-D) views of tissues and organs. A procedure that uses a computer linked to an X-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create three-dimensional (3-D) views of tissues and organs. A dye may be injected into a vein or swallowed to help the tissues and organs show up more clearly. This scan may be used to help diagnose disease, plan treatment or find out how well treatment is working. Cytogenetic test The process of analyzing cells in a sample of tissue, blood, bone marrow or amniotic fluid to look for changes in chromosomes, including broken, missing, rearranged or extra chromosomes. The process of analyzing cells in a sample of tissue, blood, bone marrow or amniotic fluid to look for changes in chromosomes, including broken, missing, rearranged or extra chromosomes. Changes in certain chromosomes may be a sign of a genetic disease or condition or some types of cancer. Cytogenetic analysis may be used to help diagnose disease, plan treatment or find out how well treatment is working. Flow cytometry A laboratory method that measures the number of cells, the percentage of live cells and certain characteristics of cells in a sample of blood, bone marrow or other tissue. A laboratory method that measures the number of cells, the percentage of live cells and certain characteristics of cells (such as size and shape) in a sample of blood, bone marrow or other tissue. The presence of tumor markers, such as antigens, on the surface of the cells is also measured. The cells are stained with a light-sensitive dye, placed in a fluid and then passed one at a time through a beam of light. The measurements are based on how the stained cells react to the beam of light. Flow cytometry is used in basic research and to help diagnose and manage certain diseases, including cancer. Imaging In medicine, a process that makes pictures of areas inside the body. Imaging uses methods such as X-rays (high-energy radiation), ultrasound (high-energy sound waves) and radio waves. Lymphocyte A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes (white blood cells) are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. Magnetic resonance imaging A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or X-ray. MRI is especially useful for imaging the brain, the spine, the soft tissue of joints and the inside of bones. Peripheral blood smear A procedure in which a sample of blood is viewed under a microscope to count different circulating blood cells (such as red blood cells, white blood cells or platelets) and see whether they look normal. Polymerase chain reaction A laboratory method used to make many copies of a specific piece of DNA from a sample. It allows very small amounts of DNA to be amplified so they can be detected. A laboratory method used to make many copies of a specific piece of DNA from a sample that contains very tiny amounts of that DNA. Polymerase chain reaction allows these pieces of DNA to be amplified so they can be detected. Polymerase chain reaction may be used to look for certain changes in a gene or chromosome, which may help find and diagnose a genetic condition or a disease, such as cancer. It may also be used to look at pieces of the DNA of certain bacteria, viruses or other microorganisms to help diagnose an infection. Sign In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. Some examples of signs are fever, swelling, skin rash, high blood pressure and high blood glucose. Ultrasound A procedure that uses high-energy sound waves to look at tissues and organs inside the body. The sound waves make echoes that form pictures of the tissues and organs on a computer screen. A procedure that uses high-energy sound waves to look at tissues and organs inside the body. The sound waves make echoes that form pictures of the tissues and organs on a computer screen (sonogram). Ultrasound may be used to help diagnose diseases, such as cancer. It may also be used during pregnancy to check the fetus (unborn baby) and during medical procedures, such as biopsies. Also called ultrasonography.

Stages

Doctors use a system called the Rai system to determine the stage of your CLL, which helps them plan your treatment. This staging system is unique to CLL. (For SLL, doctors use a different staging system, like the system for Hodgkin or non-Hodgkin lymphoma.) 

  • The stage of your disease is based on the number of lymphocytes, red blood cells and platelets in your bone marrow and bloodstream, and whether your spleen, liver and lymph nodes are affected. 
  • The stages range from stage 0 through stage IV, with 0 being the least advanced and IV being the most advanced.
  • Your Rai stage gives your doctor information about the likelihood that the disease may progress and require treatment. Stage 0 is low risk, stages I-II are intermediate risk, and stages III-IV are high risk.

Your doctor will carefully consider many other factors to predict the outlook for your disease and select the best treatment options for you, including:

  • Chromosomal and genetic abnormalities or mutations in the leukemic cells (such as missing part of a chromosome or having an extra chromosome)
  • The presence of an IGHV mutation (immunoglobulin heavy-chain variable region gene mutation status)
  • Whether you have symptoms
  • Your age, general health, treatment preferences and lifestyle
  • The number of pre-leukemic cells
  • How quickly the leukemic cells reproduce
  • How your disease responds to initial treatment and how long the response lasts

A careful physical exam and evaluation of your bone marrow and blood are used to assess your response to treatment.

  • Remission means that your disease responds to treatment. Complete remission means no symptoms or clinical signs of disease. Partial remission means 50 percent reduction in symptoms and signs.
  • Relapsed means CLL that returns after being in remission for longer than six months.
  • Refractory means the disease progresses within six months of treatment.
Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Chromosome Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. Gene The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. Lymphocyte A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes (white blood cells) are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. Lymphoma Cancer that begins in the cells of the immune system. There are two basic categories of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas. Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer. Mutation Any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; mutations that occur in other types of cells are not inherited. Certain mutations may lead to cancer or other diseases. A mutation is sometimes called a variant. Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Red blood cell A type of blood cell that carries oxygen in the body. Refractory In medicine, refractory disease is a disease or condition that does not respond to treatment. Relapse The recurrence (return) of disease after an apparent recovery. Remission A decrease in, or disappearance of, signs and symptoms of cancer. A decrease in, or disappearance of, signs and symptoms of cancer. In partial remission, some (but not all) signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body. Sign In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. Some examples of signs are fever, swelling, skin rash, high blood pressure and high blood glucose. Spleen An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells and destroys old blood cells. It is on the left side of the abdomen near the stomach. Stage The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer and whether the cancer has spread from the original site to other parts of the body. Staging Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from where it first formed to other parts of the body. Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from where it first formed to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

How common is CLL?

About 20,000 people are diagnosed with CLL each year in the U.S. CLL is the most common leukemia in adults, accounting for almost 40% of cases. 

What causes CLL?

Doctors do not know what causes CLL. The disease is more common in people who are middle-aged or older. The average age at diagnosis is 72. CLL is more common in males than females. 

Generally, CLL is more common in North America and Europe than in Asia. But people of Asian descent who live in the United States have the same (lower) risk as those living in Asia. This suggests to experts that the difference in risk has more to do with genetics than with factors in the environment.

There are only a few known risk factors for CLL, including:

  • Being exposed to certain chemicals, such as herbicides and pesticides
  • Having an immediate family member with CLL or a cancer of the lymph system

Keep in mind that many people who develop CLL have none of the risk factors, and most people with the risk factors do not develop the disease.