Merck Manual

Please confirm that you are not located inside the Russian Federation

honeypot link

Chronic Lymphocytic Leukemia (CLL)


Ashkan Emadi

, MD, PhD, University of Maryland;

Jennie York Law

, MD, University of Maryland, School of Medicine

Last full review/revision May 2020| Content last modified May 2020
Topic Resources

Chronic lymphocytic leukemia is usually a slowly progressing disease in which mature-appearing lymphocytes 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 does not occur 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, which indicates 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 cells, resulting in a decreased number of red blood cells and a decreased number of normal white blood cells and platelets in the blood. The level of antibodies, proteins that help fight infections, also decreases. 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.

In the great majority of cases, CLL is a disorder of B lymphocytes ( B cells B cells B cells ).

Did You Know...

  • Chronic lymphocytic leukemia does not occur 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 generally do not occur until late in the course of the disease.

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.

Prognosis of 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) or a low number of platelets 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.

For reasons probably related to changes in the immune system, people who have CLL are more likely to develop other cancers, such as skin or lung cancers. CLL can also transform into a more aggressive type of cancer of the lymphatic system ( 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 ).

Treatment of CLL

  • Chemotherapy

  • Immunotherapy

Because CLL progresses slowly, many people do not need treatment for years—until the number of lymphocytes begins to increase and cause symptoms, the lymph nodes begin to enlarge, or 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. For B-cell 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 newer 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 people with 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.

Treatment of CLL symptoms

Anemia due to a decreased number of red blood cells 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). Low platelet counts are treated with platelet transfusions, and 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.

More Information about CLL

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

quiz link

Test your knowledge

Take a Quiz!