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.

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. 

Understanding your bone marrow and blood

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

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. 

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.
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

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.

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.

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.

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.