Chronic lymphocytic leukemia

Chronic lymphocytic leukemia
Other namesB-cell chronic lymphocytic leukemia (B-CLL)[1]
Chronic lymphocytic leukemia.jpg
Peripheral blood smear showing CLL cells
SpecialtyHematology and oncology
SymptomsEarly: None[2]
Later: Non-painful lymph nodes swelling, feeling tired, fever, weight loss[2]
Usual onsetOlder than 50[3]
Risk factorsFamily history, Agent Orange, certain insecticides[2][4]
Diagnostic methodBlood tests[5]
Differential diagnosisMononucleosis, hairy cell leukemia, acute lymphocytic leukemia, persistent polyclonal B-cell lymphocytosis[5]
TreatmentWatchful waiting, chemotherapy, immunotherapy[4][5]
PrognosisFive-year survival ~83% (US)[3]
Frequency904,000 (2015)[6]
Deaths60,700 (2015)[7]

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).[2][8] Early on there are typically no symptoms.[2] Later non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur.[2][9] Enlargement of the spleen and low red blood cells (anemia) may also occur.[2][4] It typically worsens gradually over years.[2]

Risk factors include having a family history of the disease.[2] Exposure to Agent Orange and certain insecticides might also be a risk.[4] CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood.[4] These cells do not function well and crowd out healthy blood cells.[2] CLL is divided into two main types: those with a mutated IGHV gene and those without.[4] Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells.[5]

Management of early disease is generally with watchful waiting.[5] Infections should more readily be treated with antibiotics.[4] In those with significant symptoms, chemotherapy or immunotherapy may be used.[4] As of 2019 ibrutinib is often the initial medication recommended.[10] The medications fludarabine, cyclophosphamide, and rituximab were previously the initial treatment in those who are otherwise healthy.[11]

CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths.[6][7] The disease most commonly occurs in people over the age of 50.[3] Males are affected more often than females.[3] It is much less common in people from Asia.[4] Five-year survival following diagnosis is approximately 83% in the United States.[3] It represents less than 1% of deaths from cancer.[7]

Signs and symptoms

A diagram showing the cells affected by CLL

Most people are diagnosed as having CLL based on the result of a routine blood test that shows a high white blood cell count, specifically a large increase in the number of circulating lymphocytes.[9] These people generally have no symptoms.[9] Less commonly, CLL may present with enlarged lymph nodes.[9] This is referred to as small lymphocytic lymphoma. Less commonly the disease comes to light only after the cancerous cells overwhelm the bone marrow resulting in low red blood cells, neutrophils, or platelets.[9] Or there is fever, night sweats, weight loss, and the person feels tired.[9]

CLL is, in virtually all cases, preceded by a particular subtype of monoclonal B-cell lymphocytosis (MBL). This subtype, termed chronic lymphocytic leukemia/small lymphocyte lymphoma MBL (CLL/SLL MBL) is an asymptomatic, indolent, and chronic disorder in which individuals exhibit an increase in the number of circulating B-cell lymphocytes. These B-cells are abnormal: they are monoclonal, i.e. produced by a single ancestral B-cell, and have some of the same cell marker proteins, chromosome abnormalities, and gene mutations found in CLL.[12][13] CLL/SLL MBL consist of two groups: low-count CLL/SLL MBL has monoclonal B-cell blood counts of <0.5x9 cells/liter (i.e. 0.5x9/L) while high-count CLL/SLL MBL has blood monoclonal B-cell counts ≥0.5x9/L but <5x109/L.[14] Individuals with blood counts of these monoclonal B-cells >5x9/L are diagnosed as having CLL. Low-count CLL/SLLL MBL rarely if ever progresses to CLL while high-count CLL/SLL MBL does so at a rate of 1-2% per year. Thus, CLL may present in individuals with a long history of having high-count CLL/SLL MBL. There is no established treatment for these individuals except monitoring for development of the disorder's various complications (see treatment of MBL complications) and for their progression to CLL.[15][16]

Complications

Complications include a low level of antibodies in the bloodstream (hypogammaglobulinemia) leading to recurrent infection, warm autoimmune hemolytic anemia in 10–15% of patients, and bone marrow failure. Chronic lymphocytic leukemia may also transform into Richter's syndrome, the development of fast-growing diffuse large B cell lymphoma, prolymphocytic leukemia, Hodgkin's lymphoma, or acute leukemia in some patients. Its incidence is estimated to be around 5% in patients with CLL.[17]

Gastrointestinal (GI) involvement can rarely occur with chronic lymphocytic leukemia. Some of the reported manifestations include intussusception, small intestinal bacterial contamination, colitis, and others. Usually, GI complications with CLL occur after Richter transformation. Two cases to date have been reported of GI involvement in chronic lymphocytic leukemia without Richter's transformation.[18]