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Chronic Lymphocytic Leukemia (CLL)


Ashkan Emadi

, MD, PhD, University of Maryland;

Jennie York Law

, MD, University of Maryland, School of Medicine

Reviewed/Revised Oct 2023
Topic Resources

Chronic lymphocytic leukemia is usually a slowly progressing disease in which mature-appearing lymphocytes (a type of white blood cell White Blood Cells The main components of blood include Plasma Red blood cells White blood cells Platelets read more White Blood Cells ) become cancerous and gradually replace normal cells in lymph nodes.

  • People may have no symptoms, or they may have general symptoms such as tiredness, fever, night sweats, and unintended weight loss.

  • People may also have enlarged lymph nodes and a sense of abdominal fullness due to enlargement of the spleen.

  • Blood tests are needed for diagnosis.

  • Treatment includes chemotherapy drugs, monoclonal antibodies, and sometimes radiation therapy.

More than three fourths of the people who have chronic lymphocytic leukemia (CLL) are older than 60, and the disease is extremely rare in children. CLL is the most common type of leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more in North America and Europe. It is rare in Japan and Southeast Asia and in people of Japanese and Southeast Asian descent living in the United States, which suggests that genetics plays some role in its development.

The number of cancerous, mature-appearing lymphocytes increases first in the blood, bone marrow, and lymph nodes. Cancerous lymphocytes then spread to the liver and spleen, both of which begin to enlarge.

In the bone marrow, cancerous lymphocytes may crowd out normal blood-producing cells, resulting in a decreased number of one or more of the following:

Cancerous lymphocytes do not function like normal lymphocytes, which produce proteins (antibodies) that help fight infections. The smaller number of healthy lymphocytes that remain are not always able to produce enough antibodies, so infection is likely. Also, the immune system, which ordinarily defends the body against foreign organisms and substances, sometimes becomes misguided, reacting to and destroying normal tissues. This misguided immune activity can result in the destruction of red blood cells, neutrophils, or platelets.

CLL can sometimes transform into an aggressive cancer called lymphoma Overview of Lymphoma Lymphomas are cancers of lymphocytes, which reside in the lymphatic system and in blood-forming organs. Lymphomas are cancers of a specific type of white blood cells known as lymphocytes. These... read more Overview of Lymphoma . This type of transformation, called Richter's transformation, happens in 2 to 10 percent of cases.

Did You Know...

  • Chronic lymphocytic leukemia only rarely occurs in children.

Symptoms of CLL

In early stages of CLL, most people have no symptoms, and the disease is diagnosed only because of an increased white blood cell count. Later symptoms may include

  • Enlarged lymph nodes

  • Fatigue

  • Loss of appetite

  • Weight loss

  • Night sweats

  • Shortness of breath when exercising

  • A sense of abdominal fullness resulting from an enlarged spleen

As CLL progresses, people may appear pale and bruise easily. Bacterial, viral, and fungal infections may occur late in the course of the disease as the bone marrow produces fewer healthy white blood cells to fight infection.

Diagnosis of CLL

  • Blood tests

Sometimes CLL is discovered accidentally when blood counts ordered for some other reason show an increased number of lymphocytes. Specialized blood tests (called flow cytometry and immunophenotyping) to characterize the abnormal lymphocytes can be done on the cells in the blood. Blood tests also may show that the numbers of red blood cells, platelets, and antibodies are low.

Treatment of CLL

  • Chemotherapy

  • Immunotherapy

Because CLL progresses slowly, many people do not need treatment for years, Doctors usually wait to begin treatment until one or more of the following occur

  • The number of lymphocytes begins to increase and cause symptoms

  • The lymph nodes, liver, or spleen enlarge

  • The number of red blood cells or platelets decreases

Drug treatment of CLL

There is no standard combination of drugs that is used for CLL. Initial drug treatment usually includes drugs such as fludarabine and cyclophosphamide, which kill cancer cells by interacting with DNA. Currently, chemotherapy and a monoclonal antibody called rituximab are also used to treat CLL. This combination therapy usually is successful in controlling CLL (inducing remission). Eventually, most CLL becomes resistant to these drugs. Treatments with other drugs or other monoclonal antibodies are then considered.

Ibrutinib is a drug that has induced lasting remissions in some people with CLL. It can be used for initial treatment or for CLL that is unlikely to respond to other treatments, for CLL that fails to respond to other treatment (refractory), or for CLL that has relapsed. Obinutuzumab may be used in older adults with both CLL and other illnesses. Sometimes, stem cell transplantation Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more can be done in people who have relapsed.

Acalabrutinib and zanubrutinib have recently become available to treat CLL. They may cause fewer side effects than ibrutinib.

Treatment of CLL symptoms

Anemia is treated with blood transfusions Overview of Blood Transfusion A blood transfusion is the transfer of blood or a blood component from one healthy person (a donor) to a sick person (a recipient). Transfusions are given to increase the blood's ability to... read more Overview of Blood Transfusion and occasionally with injections of erythropoietin or darbepoietin (drugs that stimulate red blood cell formation). A low platelet count may cause bleeding and is treated with platelet transfusions. Infections are treated with antimicrobials. Radiation therapy is used to shrink enlarged lymph nodes or an enlarged liver or spleen if the enlargement is causing discomfort and chemotherapy is ineffective.

Chronic Lymphocytic Leukemia

Prognosis for CLL

Usually CLL progresses slowly. Doctors determine how far the disease has progressed (staging) to predict the survival time. Staging is based on several factors, including the

  • Number of lymphocytes in the blood

  • Number of lymphocytes in the bone marrow

  • Size of the spleen

  • Size of the liver

  • Number of red blood cells in the blood

  • Number of platelets in the blood

People who are in the early stages of CLL often survive 10 to 20 years or longer after the diagnosis is made and usually do not need treatment in the early stages. People who have a low number of red blood cells (anemia Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more ) or a low number of platelets (thrombocytopenia Overview of Thrombocytopenia Thrombocytopenia is a low number of platelets (thrombocytes) in the blood, which increases the risk of bleeding. Thrombocytopenia occurs when the bone marrow makes too few platelets or when... read more Overview of Thrombocytopenia ) need more immediate treatment and have a less favorable prognosis. Usually, death occurs because the bone marrow can no longer produce a sufficient number of normal cells to carry oxygen, fight infections, and prevent bleeding.

More Information

The following English-language resource may be useful. Please note that the MANUAL is not responsible for the content of this resource.

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