What is Chronic Lymphocytic Leukemia (CLL)?

Chronic lymphocytic leukemia is a blood cancer that occurs when the bone marrow produces too many lymphocytes. Found in the blood and lymphatic tissues throughout the body, lymphocytes are white blood cells that help the immune system fight off infection and disease.

Chronic lymphocytic leukemia is similar to acute lymphocytic leukemia (ALL); their main differences lie in the maturity and progression of the cancer cells. CLL cells are mature, closely resemble healthy white blood cells and tend to grow slowly—sometimes over several years—leading to a gradual accumulation of abnormal cells. Some patients do not require immediate care. However, because this slow-growing leukemia can potentially spread to lymph nodes, the liver or the spleen before it is detected, it requires carefully planned and delivered treatment. CLL primarily affects older adults.

In contrast, ALL is a rapidly progressing leukemia that develops from immature white blood cells (lymphoblasts). Because severe symptoms can develop within a short timeframe, the cancer requires immediate treatment. Although acute lymphocytic leukemia can occur at any age, it is more common among children than adults.

What causes chronic lymphocytic leukemia?

While the precise causes of CLL are unknown, scientists have determined that the cancer results from changes that take place at a cellular level. Specifically, healthy lymphocytes undergo harmful changes that cause the cells to grow uncontrollably, live longer than they should and build up in the bone marrow. The leukemia cells may then enter the bloodstream, travel throughout the body and spread to various organs and tissues.

What are the risk factors for chronic lymphocytic leukemia?

Unlike many other cancers, CLL has not been conclusively linked to lifestyle factors, such as poor nutrition and tobacco use, or any particular infections. The few known risk factors for chronic lymphocytic leukemia are:

• Age – Approximately 90% of cases are diagnosed after age 50.
• Family history – Individuals with a parent, sibling or child who was diagnosed with CLL are at twice the risk of developing the condition themselves.
• Exposure to certain chemicals – Studies have connected CLL to radon in the home, certain pesticides used in farming and Agent Orange, an herbicide used during the Vietnam War.

What are the signs and symptoms of chronic lymphocytic leukemia?

Early-stage CLL may not have noticeable symptoms. In many cases, the condition is diagnosed after a high lymphocyte count is detected in a blood test performed for an unrelated reason.

The initial warning signs of chronic lymphocytic leukemia are often vague, such as:

• Unusual tiredness
• Unexplained weight loss
• Fever, chills and night sweats
• Swollen or enlarged lymph nodes
• Abdominal pain or fullness (caused by liver or spleen enlargement)

As CLL progresses, leukemia cells may begin to crowd out healthy red blood cells, white blood cells and platelets. As these cells are depleted, additional symptoms may develop, such as:

• Overwhelming fatigue, muscle weakness and shortness of breath caused by a low red blood cell count (anemia)
• Recurrent infections due to a shortage of healthy white blood cells (leukopenia)
• Excessive bruising and bleeding resulting from a low platelet count

How is chronic lymphocytic leukemia diagnosed?

Typically, CLL is diagnosed through a combination of tests, such as:

• Blood work – A complete blood count (CBC) may reveal an elevated white blood cell level, which could indicate leukemia, while a peripheral blood smear may show abnormal lymphocytes.
• Flow cytometry – Used to analyze the markers on the surface of blood cells, flow cytometry can help a physician identify leukemia cells and determine their type.
• Bone marrow biopsy – A small sample of bone marrow will be microscopically examined by a pathologist, who can identify leukemia cells and assess their quantity and type.
• Genetic testing – Certain tests can identify specific genetic abnormalities or mutations that are common in CLL, which can guide treatment decisions.
• Imaging tests – Computed tomography (CT) scans can help a physician check for enlarged lymph nodes or organs.

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How is chronic lymphocytic leukemia treated?

CLL is treated based on the stage of the cancer, the severity of the symptoms and the overall health of the patient. Common options include:

• Observation (watchful waiting) – If early-stage CLL is not causing symptoms, a physician may suggest monitoring the condition regularly without immediate treatment.
• Chemotherapy – Traditional chemo drugs can destroy or slow the growth of leukemia cells.
• Targeted therapy – Specialized drugs, such as BTK inhibitors (ibrutinib) and BCL-2 inhibitors (venetoclax), can specifically target the proteins or pathways in CLL cells that are known to promote cancer growth.
• Immunotherapy – Monoclonal antibodies (rituximab) can help the immune system recognize and attack leukemia cells.
• Bone marrow transplantation – In certain cases, a bone marrow transplant may be considered, particularly for a patient who is young or has an aggressive form of CLL.
• Radiation therapy – High-powered beams of energy may be administered to shrink enlarged lymph nodes or an enlarged spleen.

What are the possible complications of chronic lymphocytic leukemia?

Possible complications of CLL include:

• Recurrent infections – CLL weakens the immune system, making the body more susceptible to frequent or severe infections.
• Autoimmune conditions – CLL can cause the immune system to inadvertently attack healthy cells, which can lead to autoimmune hemolytic anemia if red blood cells are destroyed or immune thrombocytopenia if platelets are destroyed.
• Anemia and bleeding problems – As CLL progresses, leukemia cells can crowd out healthy blood cells, leading to anemia, fatigue and increased bleeding or bruising.
• Spleen and lymph node enlargement – CLL can cause significant and uncomfortable swelling of the spleen and lymph nodes.
• Progression to aggressive cancer – In rare cases, CLL can transform into a more serious form of lymphoma, which is known as Richter’s transformation.
• Secondary cancers – CLL patients have a heightened risk of developing secondary malignancies, such as other blood-related cancers and skin cancers.

Managing these complications is often an important aspect of CLL treatment and care.

Benefit from world-class care at Moffitt Cancer Center

At Moffitt, we have the specialized expertise necessary to effectively treat chronic lymphocytic leukemia as well as other types of leukemia and cancers of the blood and bone marrow. The multispecialty team in our Malignant Hematology Program is dedicated to researching, diagnosing and treating these complex conditions, and our patients can work with esteemed medical professionals who are among the most highly respected in their respective fields.

Several forms of CLL treatment may be required to achieve long-term remission. For instance, we may suggest a combination of chemotherapy, targeted therapies, radiation therapy and supportive care, with the specific details tailored to the patient’s unique diagnosis. Additionally, we can coordinate the various aspects of follow-up treatment and bloodwork. Consolidation therapies for CLL, such as bone marrow transplantation, can also be arranged at Moffitt.

If you would like to learn more about chronic lymphocytic leukemia, you can request an appointment with a specialist in the Blood and Marrow Transplant and Cellular Immunotherapy Program at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.