CLL has an overall incidence of about 4.2 cases per 100,000 persons per year, and the median age at diagnosis is 72 years.3 The incidence is substantially higher in people older than 80 (30 cases per 100,000 persons per year), and only about 10% of CLL cases are in persons younger than 55.3 Family members of a patient with CLL have a 6- to 9-fold increased risk of developing the disease (see Sidebar for risk factors).4-6
Pathophysiology: CLL and other leukemias
Leukemias develop because of alterations in the DNA of myeloid or lymphoid cells, but the process of development of malignant changes is not clear.
CLL is a lymphoproliferative disorder (a blood cancer) characterized by dysfunctional monoclonal B lymphocytes.1,2 Small lymphocytic lymphoma (SLL) is considered the same disease, differing only in the sites of involvement. Whereas malignant B lymphocytes are primarily located in the lymph nodes and lymphoid tissue (such as the spleen and the tonsils) in SLL, they are present primarily in the bloodstream in CLL.7 This type of leukemia is classified “chronic” rather than “acute”, because of the slow speed at which abnormal leukocytes proliferate, and “lymphocytic” rather than “myelogenous”, based on the cell lineage (ie, lymphocyte vs myelocyte).4
The 3 other major subtypes of leukemia are
- Acute myelogenous leukemia (AML), the most common acute leukemia in adults. AML is an aggressive disease with a prognosis that varies with molecular subtype.
- Acute lymphoblastic leukemia (ALL), which accounts for about 80% of leukemia in children.
- Chronic myelogenous leukemia (CML), which is commonly due to a reciprocal translocation and fusion of BCR on chromosome 22 and ABL1 on chromosome 9.4
Symptoms of CLL
Many persons with CLL are asymptomatic in the early stages of the disease.3,4 As the disease progresses, nonspecific symptoms develop and include4
- Enlarged, painless lymph nodes
- Pain in the upper left portion of the abdomen, primarily due to an enlarged spleen
- Night sweats
- Weight loss
Patients with CLL will typically develop frequent infections because an excess of leukemic cells reduces the number of functional leukocytes.2,3 Some patients may develop autoimmune hemolytic anemia or autoimmune thrombocytopenia because of alterations of the immune system.2,3
Routine screening for CLL is not included in any current recommendations.3,5 In many persons, diagnosis of CLL is made when abnormal leukocytosis is seen on a routine complete blood count (CBC).4 Laboratory diagnosis of CLL is based on (1) the presence of ≥5×109/L monoclonal B lymphocytes in the peripheral blood, and (2) circulating B lymphocyte clonality confirmed by flow cytometry.3 Peripheral blood smears should be examined by a hematopathologist who can identify leukemic cells characteristic of CLL.5 A bone marrow biopsy is typically only required when immunotyping of peripheral blood (flow cytometry of leukocyte subsets) is inconclusive.3