Chronic Lymphocytic Leukemia and Hairy-Cell Leukemia

Chronic lymphocytic leukemia (CLL) is a clonal malignancy that results from expansion of the mature lymphocyte compartment. This expansion is a consequence of prolonged cell survival, rather than increased cellular proliferation. The affected lymphocytes are of B-cell lineage. Previously some cases were diagnosed as T-cell CLL but we now view those diseases as distinct entities and do not refer to them as CLL.

CLL is the most common leukemia in adults in Western countries, accounting for approximately 25% to 30% of all leukemias. The proportion of cases diagnosed with the early stages of the disease (Rai stage 0) has risen from 10% to 50%, probably because of earlier diagnosis (routine automated blood counts).

The incidence of CLL in the general population is 4.2:100,000 population, with an estimated death rate of 1.1:100,000 population. It was estimated that there will be 14,570 patients diagnosed with CLL in 2011 in the United States.

The male-to-female ratio is 2:1. There is little change with age, as the male-to-female ratio is 2.1:1 for patients < 65 years old, compared with 1.9:1 for those = 65 years old.

The median age at diagnosis is 72 years, and 70% of patients are > 65 years of age at diagnosis. CLL is rarely seen in younger patients, with < 2% being younger than 45 at the time of diagnosis.

In the American population, the incidence of CLL is similar in different races. However, the incidence is much lower in Asia (Japan, Korea, and China), Latin America, and Africa than in the United States and Western Europe.

The etiology of CLL is unclear. However, some factors associated with CLL have been identified.

There is a familial risk for CLL, with family members of patients with CLL having a twofold to sevenfold higher risk of developing the disease. CLL with a familial association tends to occur in younger individuals with subsequent generations, perhaps because of increased screening. Association with certain human lymphocyte antigen (HLA) patterns has not been consistent, and ongoing studies are attempting to identify susceptibility genes for CLL.

There is no documented association of CLL with exposure to radiation, alkylating agents, or known leukemogenic chemicals. However, exposure to some chemicals used in agriculture may increase the risk of developing CLL.

Associations between CLL and several viruses, including human T-cell lymphotrophic viruses I and II (HTLV-I and HTLV-II) and Epstein-Barr virus, have been suggested. However, no conclusive evidence of a causal relationship exists. Adult T-cell leukemia/lymphoma, a T-cell disorder that can resemble CLL, is caused by HTLV-I.

Recent studies suggest that over 4% of the population over 40 years of age harbors a population of clonal B cells with the phenotype of CLL or another B-cell malignancy, a condition now called monoclonal B-cell lymphocytosis (MBL). These asymptomatic individuals have no clinical evidence of disease and do not fulfill diagnostic criteria for CLL. All cases of CLL appear to be preceded by MBL, but most patients with MBL will not develop a hematologic malignancy.

In one study, 5.1% of patients > age 62 in the general population had monoclonal CLL-phenotype B cells. These asymptomatic individuals did not have lymphocytosis or clinical evidence of disease and did not fulfill diagnostic criteria for CLL. Whether or not these individuals will eventually develop diagnostic criteria or symptomatic disease is unknown. In that same study, patients with lymphocytosis (> 4,000 lymphocytes/µL) who developed CLL requiring treatment developed it at the rate of 1.1% per year.

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