Chronic Lymphocytic Leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is a type of cancer in your blood. It’s the most common form of leukemia in adults. Currently, healthcare providers don’t have treatments to cure chronic lymphocytic leukemia. But they do have treatments to put the condition into remission, meaning you don’t have CLL symptoms or signs of it.

Overview

What is chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) is a type of blood cancer. It’s the most common form of leukemia in adults. It happens when healthy white blood cells (lymphocytes) in your bone marrow mutate, or change, into cancerous cells that multiply and crowd out healthy blood cells and platelets.

CLL typically affects people aged 65 and older, but it can affect people starting at age 30. You can have chronic lymphocytic leukemia without having symptoms. Most people learn they have CLL after having blood tests as part of routine physical examinations.

Currently, healthcare providers don’t have routine treatments to cure chronic lymphocytic leukemia. During the past 10 years, providers have developed treatments that put CLL into remission. (Remission means you don’t have symptoms and signs of CLL.) These treatments are helping people with CLL live longer.

Types of chronic lymphocytic leukemia

You may develop CLL in your B-cells or T-cells, which are white blood cells (lymphocytes):

  • B lymphocytes (B-cells) make antibodies. Antibodies are proteins that target viruses, bacteria and cancer cells, among other foreign intruders.
  • T lymphocytes (T-cells) control your body’s immune system response. T-cells directly attack and destroy abnormal cells, including cancer cells.

Nearly all people with CLL have B-cell chronic lymphocytic leukemia. There’s a related condition that affects T-cells called T-cell prolymphocytic leukemia (PLL). People with T-cell PLL develop symptoms more quickly than people who have B-cell CLL.

How common is this condition?

Chronic lymphocytic leukemia is one of the most common types of leukemia in adults. It affects about 5 in 100,000 people in the U.S. The American Cancer Society estimates about 18,700 people will be diagnosed with CLL in 2023. By comparison, more than 238,000 people will be diagnosed with lung cancer in 2023 (one of the most common cancers overall).

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Symptoms and Causes

What are the symptoms of chronic lymphocytic leukemia?

You can have chronic lymphocytic leukemia without symptoms. It may take months to years before you notice CLL symptoms. Common symptoms include:

What causes chronic lymphocytic leukemia?

Chronic lymphocytic leukemia happens when certain chromosomes and genes mutate or change during your lifetime. Medical researchers don’t know what triggers those changes, but they’ve identified some risk factors, including:

  • Family history: Studies show people with close relatives who have CLL, such as their biological parent, siblings or children, are two to four times more likely to develop CLL.
  • Age: On average, people are 71 years old when they’re diagnosed.
  • Sex: Men and people assigned male at birth (AMAB) develop CLL more often than women and people assigned female at birth (AFAB).
  • Exposure to Agent Orange: Studies show links between CLL and Agent Orange, a chemical used during the Vietnam War.
  • Monoclonal B-cell lymphocytosis: In this condition, you have a higher-than-normal number of identical B-cells in your blood. If you have this condition, there’s a slight risk you may develop CLL.
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What are the complications of chronic lymphocytic leukemia?

Chronic lymphocytic leukemia affects your red blood cells, white blood cells and platelets. Red blood cells carry oxygen throughout your body. White blood cells protect you from infection. Platelets help your blood to clot. Without healthy blood cells and platelets, you may develop the following complications:

  • Lymphoma: About 2% to 10% of people with CLL develop lymphoma.
  • Skin cancer, lung cancer or colon cancer: You may have an increased risk for cancer because CLL affects your immune system’s ability to protect you from intruders, including cancerous cells.
  • Anemia: You may develop anemia because you don’t have enough red blood cells carrying oxygen throughout your body.
  • Thrombocytopenia: Chronic lymphocytic leukemia may affect your platelet supply.
  • Frequent infections: You may have an increased risk of bacterial, fungal or viral infections because you don’t have enough healthy white blood cells.
  • Autoimmune diseases: Some people with CLL may develop autoimmune hemolytic anemia.

Diagnosis and Tests

How is chronic lymphocytic leukemia diagnosed?

Your healthcare provider will ask about your symptoms. They’ll do a physical examination, and may order the following tests:

  • Complete blood count (CBC) with differential: A complete blood count measures the number of red blood cells, white blood cells and platelets in your blood. It also assesses how much hemoglobin (protein that carries oxygen) your red blood cells have.
  • Peripheral blood smear: A medical pathologist examines your blood cells under a microscope to look for cancerous blood cells.
  • Flow cytometry: Providers use this lab test to learn more about your blood cells. In CLL, they use flow cytometry to determine if your white blood cells carry CLL cells.
  • Genetic tests: Pathologists use tests such as fluorescent in situ hybridization (FISH) and immunoglobulin heavy chain (IGHV) to examine your chromosomes and genes. Understanding how chromosomes and genes mutated or changed helps providers determine how to treat CLL.

Stages of chronic lymphocytic leukemia

Healthcare providers use cancer staging systems to develop treatment plans and prognoses (expected outcome). Providers stage CLL with two similar staging systems. The Rai staging system categorizes CLL by the likelihood the condition will get worse and require treatment. The Binet system stages CLL by how much the condition has spread throughout your body.

Rai staging system

The Rai staging system categories are:

  • Low risk (formerly known as Rai stage 0): You have lymphocytosis and abnormal white blood cells in your blood and/or bone marrow.
  • Intermediate risk (formerly known as Rai stage I or stage II): You have lymphocytosis, enlarged lymph nodes and an enlarged spleen and/or liver.
  • High risk (formerly known as Rai Stage III): You have anemia or thrombocytopenia.
Binet staging system

The Binet staging system uses information about your blood cell and platelet count and the number of areas in your body with swollen lymph nodes. Binet staging system categories are:

  • Stage A: You don’t have anemia (low red blood cells) or low platelet levels, but you have swollen lymph nodes in at least two areas in your body. For example, you have swollen lymph nodes in your neck and groin.
  • Stage B: There are swollen lymph nodes in three areas of your body, liver or spleen, but you don’t have anemia and your platelet levels are normal.
  • Stage C: You have anemia, as well as swollen lymph nodes, in three or more areas of your body.

Some people with cancer feel intimidated or unnerved by systems that seem to reduce their condition to a formula of numbers and letters. Your providers understand why you may feel this way. If you’re confused or concerned by what you’re hearing, ask your provider to explain how the cancer staging system works in your situation.

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Management and Treatment

How is chronic lymphocytic leukemia treated?

Treatment varies based on your symptoms and test results. For example, if you have early-stage CLL, your healthcare provider may opt for watchful waiting (active surveillance).

In watchful waiting, providers hold off on treatment while carefully monitoring your overall health, symptoms and test results.

Providers also consider genetic test results. For example, certain genetic changes mean your condition is likely to get worse sooner rather than later or typical CLL treatments won’t be as effective.

Common CLL treatments include targeted therapy and chemotherapy. Providers may use radiation therapy to ease CLL symptoms. Each treatment type may cause different side effects. Your provider will outline specific treatment benefits, side effects and potential long-term complications.

Targeted therapy

This treatment works by targeting or focusing on cancer cells. In chronic lymphocytic leukemia, treatments keep cancerous white blood cells from growing. Some targeted treatments destroy the cells without hurting healthy cells or platelets. Specific treatments or medication may include:

  • Bruton’s tyrosine kinase (BTK) inhibitor therapy: This treatment blocks the enzymes that cause B-cells to develop into excess white blood cells. Examples include ibrutinib (Imbruvica®), acalabrutinib (Calquence®) and zanubrutinib (Brukinsa ®).
  • BCL2 inhibitor therapy: Venetoclax (Venclexta®) blocks BCL2, a protein found on leukemia cells, including CLL cells. This treatment can destroy leukemia cells or make them more sensitive to other cancer drugs.
  • Monoclonal antibody therapy: This treatment is a type of immunotherapy. Monoclonal antibodies are lab-made antibodies that block cancer cell growth or destroy cancerous cells. Examples of monoclonal antibody therapy medications include rituximab (Rituxan®) and obinutuzumab (Gazyva®).

Chemotherapy

Your healthcare provider may use chemotherapy as an initial treatment for chronic lymphocytic leukemia. Common chemotherapy drugs for CLL include:

Immunotherapy

This treatment works by restoring or strengthening your immune system so it can do more to kill cancerous cells or slow down cancerous cell growth.

Providers may use the immunotherapy drug lenalidomide (Revlimid®) to treat chronic lymphocytic leukemia that hasn’t responded to chemotherapy, CLL that’s come back (recurrent CLL) or CLL that’s getting worse.

Medical researchers are evaluating chimeric antigen receptor (CAR-T) therapy for people with CLL that hasn’t responded to standard treatment.

Prevention

Can this condition be prevented?

There’s no known way to prevent CLL.

Outlook / Prognosis

How long can you live with chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) typically develops very slowly. You can live for a long time with CLL before you notice symptoms. When you do, healthcare providers have very effective treatments that put CLL into remission. Remission from CLL typically lasts for several years before the condition comes back. Even then, your provider may recommend different treatments that put CLL back into remission. CLL never goes away, but people can still live a long and full life with the disease.

What is the overall survival rate for chronic lymphocytic leukemia?

The National Cancer Institute estimates 87.9% of people with CLL are alive five years after diagnosis. When you think about survival rates, it’s important to remember survival rates are estimates based on the experiences of large groups of people with CLL. Many things may affect CLL survival rates, from your overall health and the condition stage at diagnosis, to how your condition responds to treatment. If you have questions, ask your provider what you can expect in your situation.

What happens in end-stage chronic lymphocytic leukemia?

The term “end-stage” means treatment no longer works to slow or stop CLL. In that case, you may develop life-threatening infections or uncontrollable bleeding that healthcare providers aren’t able to cure.

Living With

What’s it like to live with chronic lymphocytic leukemia?

That depends on your situation. You can have CLL without having any symptoms. If you have symptoms, there are treatments to reduce them and manage your condition, but it never goes away.

Here are some suggestions for living with CLL:

  • Protect yourself from infection. People with CLL have an increased risk of infection, some of which could be life-threatening. Ask your healthcare provider which vaccinations make sense.
  • Monitor your overall health. You may be at increased risk for skin cancer, lung cancer or colon cancer. Ask your provider about cancer screening tests.
  • Manage your stress. Many people with CLL go through cycles of remission and relapse. Cycling through remission and relapse may make you anxious. If that’s your situation, ask your provider about programs or services to help you to manage stress.
  • Eat a healthy diet. Some CLL symptoms may affect your appetite. Ask your provider about consulting with a nutritionist. If your appetite is fine, focus on a balanced diet of low-fat protein, grains, fruits and vegetables, and healthy fats to improve your overall health.
  • Exercise. Exercise can help you manage stress and boost your spirits.
  • Take it easy. CLL can be exhausting. Try to rest when you need a break.
  • Know what to expect. Knowledge is power. Ask your provider about symptoms that could be signs your condition is progressing (getting worse). Your provider may recommend different treatments that do more to manage CLL.

What questions should I ask my healthcare provider?

You may want to ask:

  • What type of chronic lymphocytic leukemia do I have?
  • I don’t have symptoms. When should I start treatment?
  • What are my treatment options?
  • Will I always need treatment?
  • Will treatment put my condition into remission?

A note from Cleveland Clinic

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. You can have chronic lymphocytic leukemia for years without having any symptoms. If you have CLL, you may not need treatment right away. Healthcare providers can’t cure it, but they can provide treatments to eliminate CLL symptoms and signs of disease, putting the disease into remission. Some people with CLL live for many years. Living with a chronic illness like CLL isn’t always easy. You may go through several cycles of remission and recurrence. With each cycle, you may worry about what’s next. Your providers understand what it’s like to live with a chronic illness. They’ll be glad to answer any questions and help you as much as they can.

Medically Reviewed

Last reviewed by a Cleveland Clinic medical professional on 01/31/2023.

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