Definition
Cancer begins when cells start to grow uncontrollably. These abnormal cells can originate in almost any part of the body and have the potential to spread to other areas. For more information on how cancer develops and spreads, please refer to the “What Is Cancer?” section.
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults. It is a type of cancer that originates in the bone marrow’s lymphocytes, a type of white blood cell. Initially, the cancerous cells start in the bone marrow but eventually enter the bloodstream.
In CLL, the leukemia cells typically accumulate slowly, with many individuals not experiencing any symptoms for several years. However, over time, these cells proliferate and migrate to other parts of the body, such as the lymph nodes, liver, and spleen.
What is leukemia?
Leukemia is a type of cancer that begins in the bone marrow’s blood-forming cells. When one of these cells transforms into a leukemia cell, it fails to mature properly and begins to grow uncontrollably. These abnormal cells often divide more rapidly than normal cells, and they do not die when they should. As a result, leukemia cells accumulate in the bone marrow, displacing normal cells. Eventually, leukemia cells escape into the bloodstream, increasing the number of white blood cells. Once in the blood, these cells can spread to other organs, disrupting normal cellular functions.
Leukemia differs from other types of cancer that originate in organs like the lungs, colon, or breast and then spread to the bone marrow. Cancers that begin elsewhere and then spread to the bone marrow are not classified as leukemia.
Precise identification of the leukemia type helps doctors predict each patient’s prognosis more accurately and choose the most appropriate treatment.
What is chronic leukemia? Chronic leukemia is characterized by cells that partially mature (resembling normal white blood cells) but do not complete the maturation process. Although these cells may appear relatively normal, they are not as effective in fighting infections as normal white blood cells. Leukemia cells also have a longer lifespan than normal cells, leading to an accumulation that crowds out normal cells in the bone marrow. Chronic leukemias can take years to cause noticeable symptoms, and many individuals can live with the condition for an extended period. However, chronic leukemias are typically more challenging to cure than acute leukemias.
What is lymphocytic leukemia?
Leukemia is classified as either myeloid or lymphocytic based on the type of bone marrow cells in which the cancer originates.
Lymphocytic leukemias, also known as lymphoid or lymphoblastic leukemia, begin in cells that develop into lymphocytes. Lymphomas, another type of cancer, also originate from these cells. The primary distinction between lymphocytic leukemias and lymphomas is that leukemia cells primarily reside in the bone marrow and blood, while lymphoma cells tend to accumulate in lymph nodes and other tissues.
The American Cancer Society’s 2024 estimates for leukemia in the United States are as follows:
- Approximately 62,770 new cases of leukemia and about 23,670 deaths from leukemia (all types).
- Around 20,700 new cases of chronic lymphocytic leukemia (CLL).
- Roughly 4,440 deaths from CLL.
CLL represents about a quarter of all new leukemia cases. The lifetime risk of developing CLL is approximately 1 in 175 (0.57%), with a slightly higher risk in men than in women.
CLL primarily affects older adults, with the average age of diagnosis being around 70 years. It is uncommon in individuals under 40 and extremely rare in children.
Black Americans often have more advanced disease and shorter survival rates.
Types of CLL
Doctors recognize two main types of CLL:
- Slow-growing CLL: Progression is gradual, and patients may not require treatment for a long time.
- Fast-growing CLL: This form is more aggressive and poses a greater health risk. Despite their similar appearance, laboratory tests can differentiate between these two types by analyzing the presence of specific proteins like ZAP-70 and CD38. Low levels of these proteins in CLL cells indicate slower growth and more favorable long-term outcomes.
Rare forms of lymphocytic leukemia While the most common CLL originates in B lymphocytes, there are rare types of leukemia with similarities to CLL:
- Prolymphocytic leukemia (PLL): This leukemia closely resembles normal prolymphocytes, immature forms of B or T lymphocytes. Both B-PLL and T-PLL tend to grow and spread faster than typical CLL. Although most individuals respond to some form of treatment, relapse is common over time. PLL may develop in individuals with pre-existing CLL, which usually results in a more aggressive form, but it can also occur in those without prior CLL.
- Large granular lymphocyte (LGL) leukemia: Another rare form of chronic leukemia, LGL leukemia involves large cancerous cells with characteristics of T lymphocytes or natural killer (NK) cells. While most cases progress slowly, a small percentage are aggressive and challenging to treat, although immunosuppressive drugs may be beneficial.
- Hairy cell leukemia (HCL): This rare cancer of lymphocytes progresses slowly. The cancer cells, a type of B lymphocyte, differ from those in CLL. HCL cells are characterized by fine projections on their surface, giving them a “hairy” appearance under a microscope. Symptoms and treatment for HCL differ significantly from those of CLL, with high success rates in HCL treatment.
Causes
The exact cause of most cases of chronic lymphocytic leukemia (CLL) remains unknown, yet scientists have made significant discoveries regarding the distinctions between normal lymphocytes and CLL cells.
Human cells typically grow and function based on information stored in each cell’s chromosomes, which are lengthy molecules of DNA. DNA carries our genes, which serve as the instructions for cellular functioning and play a role in our physical traits inherited from our parents. However, genes also influence various aspects beyond appearance.
During cell division, when a cell prepares to split into two new cells, it must replicate its DNA. This process is not flawless, and errors can occur, potentially affecting genes within the DNA. Some genes regulate cell growth and division, such as oncogenes, which promote cell growth, and tumor suppressor genes, which inhibit cell division or prompt cells to die at the appropriate time. Cancers can arise from DNA mutations that activate oncogenes or deactivate tumor suppressor genes.
Each human cell contains 23 pairs of chromosomes. In CLL, a change in at least one of these chromosomes is frequently observed. This change often involves a deletion, which means losing a portion of a chromosome. The most common deletion in CLL affects part of chromosome 13, although other chromosomes like 11 and 17 can also be impacted. These alterations, known as del(13q), del(11q), or del(17p), are significant in CLL, although the specific genes involved and their role in causing leukemia are not yet fully understood.
Normal B lymphocytes, which are integral to the immune system, are programmed to proliferate when encountering foreign substances called antigens. CLL is thought to initiate when B lymphocytes continue to divide uncontrollably after encountering an antigen. However, the precise reasons for this abnormal proliferation remain unclear.
While some cancer types can be inherited due to DNA mutations passed down from a parent, inherited mutations seldom cause CLL. Instead, DNA changes associated with CLL typically occur during an individual’s lifetime.
Risk Factors
While some risk factors, like smoking, are modifiable, others, such as age or family history, cannot be altered.
However, having one or several risk factors does not guarantee the development of a disease. Some individuals with no apparent risk factors may still develop the disease, while others with multiple risk factors may not. Additionally, determining the extent to which a specific risk factor contributes to the development of cancer can be challenging.
Chronic lymphocytic leukemia (CLL) has few known risk factors, including:
Age: The risk of CLL increases with age, with the majority of cases occurring in individuals over 50 years old.
Exposure to certain chemicals: Studies suggest a potential link between exposure to Agent Orange, used in the Vietnam War, and an increased risk of CLL. Long-term exposure to specific pesticides, particularly in farming, may also be associated with a higher risk, although further research is needed for confirmation.
Radon exposure: Exposure to radon at home has been linked to an elevated risk of CLL.
Family history: First-degree relatives (parents, siblings, or children) of individuals with CLL have a higher risk of developing the disease.
Sex: CLL is slightly more common in males than females, a trend observed in leukemia overall.
Race/ethnicity: CLL is more prevalent in North America and Europe compared to Asia. Asian individuals living in the United States do not exhibit a higher risk compared to those residing in Asia, suggesting a genetic rather than environmental influence on risk differences.
Symptoms
Chronic lymphocytic leukemia (CLL) is often asymptomatic at diagnosis, with many individuals only discovering they have the condition during unrelated health tests or routine check-ups, where a high number of lymphocytes is detected in their blood.
Even when symptoms are present, they can be nonspecific and mimic those of other conditions. These symptoms do not vary by sex or gender and may include:
- Weakness
- Fatigue
- Unexplained weight loss
- Chills
- Fever
- Night sweats
- Enlarged lymph nodes (felt as lumps under the skin)
- Abdominal pain or fullness (resulting from an enlarged spleen and/or liver)
Advanced CLL can lead to various symptoms because leukemia cells replace normal blood-producing cells in the bone marrow. This can result in:
- Anemia: Characterized by a shortage of red blood cells, causing fatigue, weakness, and shortness of breath.
- Leukopenia: A deficiency of normal white blood cells increases the risk of infections. Neutropenia, a low level of neutrophils (a type of white blood cell crucial for fighting bacterial infections), is a common term used in this context. While individuals with CLL may have high white blood cell counts due to excess lymphocytes (lymphocytosis), these leukemia cells do not combat infections like normal white blood cells.
- Thrombocytopenia: A deficiency of blood platelets can lead to excessive bruising, bleeding, frequent or severe nosebleeds, and bleeding gums.
Individuals with CLL are more susceptible to infections because their immune systems are compromised. CLL affects B lymphocytes, which typically produce antibodies to fight infection. However, in CLL, these antibody-producing cells are impaired, leading to increased vulnerability to infections ranging from mild colds to severe pneumonia.
CLL can also impact the immune system in other ways. Some individuals with CLL develop abnormal antibodies that attack normal blood cells, a condition known as autoimmunity. This can result in low blood counts, with antibodies attacking red blood cells causing autoimmune hemolytic anemia, antibodies attacking platelets and their production causing low platelet counts, or antibodies attacking white blood cells causing leukopenia.
While these symptoms may be indicative of CLL, they can also stem from other conditions. Therefore, it’s crucial to consult a doctor promptly if you experience any of these symptoms for proper diagnosis and treatment.
Diagnosis
Several signs and symptoms may indicate the presence of chronic lymphocytic leukemia (CLL), but diagnostic tests are necessary for confirmation.
Medical History and Physical Examination: Your doctor will conduct a thorough medical history review to identify symptoms and potential risk factors. Family medical history and general health will also be discussed. A physical examination will be performed to detect possible signs of leukemia and other health issues, focusing on lymph nodes, the abdomen, and other affected areas.
Blood Tests: Blood samples will be drawn from a vein in your arm for various tests, including:
- Complete blood count (CBC) and peripheral blood smear: These tests assess the levels of red blood cells, white blood cells, and platelets. CLL typically presents with an elevated number of lymphocytes. A peripheral blood smear may reveal abnormal-looking lymphocytes known as smudge cells.
- Flow cytometry: This test identifies specific markers on or within cells to determine their types, aiding in CLL diagnosis and detection of abnormal cells in the bone marrow or other fluids.
Other Blood Tests: Additional blood tests may be conducted to measure certain chemical levels, assess liver or kidney issues due to leukemia cell spread or chemotherapy, check mineral levels, or evaluate prior hepatitis infection before rituximab treatment.
Bone Marrow Tests: While blood tests can diagnose CLL, bone marrow tests provide additional information on disease progression. These tests are often performed before treatment initiation and may be repeated during or after treatment. They include:
- Bone marrow aspiration and biopsy: Samples are taken from the pelvic bone using a needle to examine cellularity, the pattern of CLL cell spread, and the presence of abnormal cells.
- Routine microscopic exams: Pathologists analyze bone marrow samples under a microscope to classify cells into specific types and determine their maturity. CLL cells typically appear mature compared to the immature cells of acute leukemias.
Cytogenetics: This test examines chromosomes in bone marrow, blood, or other tissues to identify chromosomal changes characteristic of CLL, such as deletions or translocations, aiding in prognosis determination.
Fluorescent In Situ Hybridization (FISH): FISH is used to detect specific genes or chromosome changes in cells without cell growth, providing rapid results compared to cytogenetics.
Molecular Tests: These tests assess whether the gene for immunoglobulin heavy chain variable region has mutated, helping determine CLL aggressiveness.
Other Tests: Additional tests, like lymph node biopsy, lumbar puncture, or imaging tests (CT, MRI, ultrasound), may be performed to evaluate disease progression, spread, or treatment effectiveness. These tests are not used for CLL diagnosis but can aid in management.
Treatment
- Chemotherapy for Chronic Lymphocytic Leukemia
- Immunotherapy for Chronic Lymphocytic Leukemia
- Targeted Therapy Drugs for Chronic Lymphocytic Leukemia
- Supportive or Palliative Care for Chronic Lymphocytic Leukemia
- Stem Cell Transplant for Chronic Lymphocytic Leukemia
