Chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow.^[8][9] In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell.^[8][9] In patients with CLL, B cell lymphocytes can begin to collect in their blood, spleen, lymph nodes, and bone marrow.^[10][4] These cells do not function well and crowd out healthy blood cells.^[2] CLL is divided into two main types:

1. Slow-growing CLL (indolent CLL)
2. Fast-growing CLL^[11]

Many people do not have any symptoms when they are first diagnosed.^[8][2] Those with symptoms (about 5-10% of patients with CLL) may experience the following:

• Fevers
• Fatigue
• Night sweats
• Unexplained weight loss
• Loss of appetite
• Painless lymph node swelling
• Enlargement of the spleen, and/or
• A low red blood cell count (anemia).^{[10][4][2][12]}

These symptoms may worsen over time.^[8][2]

While the exact cause of CLL is unknown, having a family member with CLL increases one's risk of developing the disease.^[10][4] Environmental risk factors include exposure to Agent Orange, ionizing radiation, and certain insecticides.^[12][4] The use of tobacco is also associated with an increased risk of having CLL.^[10]

Diagnosis is typically based on blood tests that find high numbers of mature lymphocytes and smudge cells.^[5]

When patients with CLL are not experiencing symptoms (i.e. are asymptomatic), they only need careful observation.^[13] This is because there is currently no evidence that early intervention can alter the course of the disease.^[13]

Patients with CLL have an increased risk of developing serious infections.^[13] Thus, they should be routinely monitored and promptly treated with antibiotics if an infection is present.^[13]

In patients with significant signs or symptoms, treatment can involve chemotherapy, immunotherapy, or chemoimmunotherapy.^[4] The most appropriate treatment is based on the individual's age, physical condition, and whether they have the del(17p) or TP53 mutation.^[14]

As of 2024, the recommended first-line treatments include:

1. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, zanubrutinib, and acalabrutinib
2. B-cell lymphoma-2 (BCL-2) inhibitor, venetoclax, plus a CD20 antibody obinutuzumab, OR
3. BTKi (i.e. ibrutinib) plus BCL-2 inhibitor (i.e. venetoclax)^[15][16][17]

CLL is the most common type of leukemia in the Western world. It most commonly affects individuals over the age of 65, due to the accumulation of genetic mutations that occur over time.^[3][18] CLL is rarely seen in individuals less than 40 years old.^[19] Men are more commonly affected than women, although the average lifetime risk for both genders are similar (around 0.5-1%) .^[19][20] It represents less than 1% of deaths from cancer.^[7]