Chronic lymphocytic leukemia

The underlying cause of chronic lymphocytic leukemia (CLL) is not known. It is believed that CLL occurs following a pre-cancerous condition known as monoclonal B-cell lymphocytosis (MBL). However, MBL is present in 5 to 15 percent of people over the age of 60. It is not known why a very small percentage of people with MBL develop CLL.

While familial cases have been reported, no genes directly responsible for CLL have been identified. Scientists are studying specific regions of chromosomes to see if some people may inherit a genetic susceptibility to developing CLL.

Some factors appear to increase a person's risk for CLL. It is important to note that having one or more risk factors does not mean that a person will definitely develop CLL. Most people with risk factors will not develop CLL. Risk factors may include:

• Being over age 45
• Being male
• Being white
• Having other family members with CLL or other cancers of the lymph system
• Having family members who are Russian Jews or Eastern European Jews
• Being exposed to Agent Orange (an herbicide used to kill unwanted plants) during the Vietnam War

Chronic lymphocytic leukemia (CLL) is often first suspected incidentally (by chance) during a routine blood test. In some cases, signs and symptoms suggest that a person might have CLL, but tests are needed to confirm the diagnosis. The tests that are needed may differ from person to person.

Blood tests that may be used to confirm a diagnosis of CLL include:

• Complete blood count - people with CLL have too many lymphocytes (called lymphocytosis).
• Peripheral blood smear - when blood is looked at under the microscope, it might show abnormal-looking lymphocytes.
• Flow cytometry - looks for the characteristics of CLL cells, and may be used to determine the stage of the cancer.

While blood tests are often enough to diagnose CLL, other types of tests may be used for further confirmation, to see how advanced the cancer is, and/or predict a person's prognosis (outlook). These may include:

• Bone marrow aspiration and biopsy - samples of bone marrow may be taken from the back of the hip bone or other bones. The samples are looked at under the microscope and may undergo various tests.
• Lymph node biopsy - may be recommended if a lymph node has grown and there is concern the leukemia has developed into a more aggressive cancer.
• Imaging tests (ultrasound, CT scan, or MRI) - these may be done if there is concern the cancer has spread to another organ.
• Gene tests - cells from blood or bone marrow samples are grown in the lab so their chromosomes can be examined. Some cases of CLL have chromosome changes that can be seen under the microscope.

Chronic lymphocytic leukemia (CLL) is generally considered an acquired condition and usually occurs in people with no family history of CLL. However, familial cases have been reported. CLL and other cancers affecting the lymph system and blood occur more frequently in first-degree relatives of people with CLL than in the general population. There is currently no proof that CLL itself is inherited, but certain genes (or combinations of genes) may predispose a person to familial cancer, including CLL. A number different chromosomal regions are being studied to identify possible susceptibility genes for familial CLL. Having a genetic predisposition or susceptibility does not mean that a person will definitely develop CLL or another type of cancer; it means a person has an increased risk to develop cancer.

While cancer cells in CLL are found to have genetic changes or mutations, these changes are acquired (not inherited) and are limited to the cancer cells. They are called somatic mutations and are not passed on from parent to child.

The chance of recovery and life expectancy for each person depends on many factors. These include:

• The presence and type of genetic changes in CLL cells - for example, the loss of part of chromosome 13 is often associated with less aggressive disease and a better outlook, while changes in chromosomes 11 or 17 are linked to a poorer outlook.
• Whether lymphocytes are spread throughout the bone marrow - small groups of cells are associated with a better outlook than if cells are scattered throughout the marrow.
• The stage of the disease.
• Whether the CLL is improving with treatment or has recurred (come back).
• Whether the CLL develops into lymphoma or prolymphocytic leukemia.
• The person's general health.

Most people diagnosed with CLL live 5 to 10 years. Often there are few health issues for several years, followed by 1 to 2 years of progressive disease. During this time, quality of life is diminished due to both the condition and complications of treatment. About half of people diagnosed in the early stages live more than 12 years. Lastly, some people do not survive more than 2 to 3 years after the diagnosis due to complications from CLL.

The best treatment for each person with chronic lymphocytic leukemia (CLL) depends on many factors, including whether a person has symptoms, the stage of the condition, results of various tests, and whether the CLL has recurred (come back). For example, people with early stage CLL who have no symptoms may simply be closely monitored by their doctor without any treatment (watchful waiting). When a person develops symptoms, or there are signs the cancer has progressed, treatment options may include:

• Chemotherapy
• Radiation therapy
• Targeted therapy - drugs or other substances used to find and kill cancer cells without hurting normal cells. Examples include monoclonal antibody therapy, tyrosine kinase inhibitor therapy, and BCL2 inhibitor therapy.
• Blood or platelet transfusions if blood counts are low
• Bone marrow or stem cell transplantation - in younger patients with advanced or aggressive CLL
• Surgery - for example, spleen removal (splenectomy) for enlarged spleen and low blood counts

More information about the treatment of CLL can be viewed on the National Cancer Institute's page about CLL treatment.