Chronic lymphocytic leukaemia (CLL) is a malignant disorder of the white blood cells (lymphocytes). CLL causes abnormal lymphocytes to proliferate, thus impairing the production and function of red blood cells, platelets and normal lymphocytes. This in turn causes anaemia, failure of the blood to clot and increased susceptibility to infection.
There are two main types of lymphocytes called B-cells and T-cells. B-cell CLL comprises about 95% of all CLL.
Often, the disease goes undiagnosed either until it is well advanced, or until a chance test shows abnormally high levels of lymphocytes in the blood.
CLL is a chronic, life-threatening and incurable disease. It is the most common form of leukaemia in the Western world, affecting about 2.7 people in every 100,000. Predominantly, it is a disease of older people, with 75% of those diagnosed being over the age of 60 years, although 6% are below the age of 50 years. Twice as many men as women are affected.
Life expectancy depends on the stage at which the disease is diagnosed (see the section on staging systems). For those in the early stages of the disease, median life expectancy is over 10 years, while for patients with advanced disease it is only 6 to 9 months. Other adverse prognostic factors include early age of onset.
Despite the apparently better prognosis in early disease, there is no evidence that early treatment is beneficial, and it may indeed be harmful. Since many patients have limited disease, they do not require anything more than general observation, referred to as 'watchful waiting'.
When the disease progresses, a hierarchy of treatments is used. There is a trade-off between the likelihood of halting or reversing progression of the disease and the side-effects of drug treatment.
Response rates to chemotherapy of about 70% are seen in intermediate-stage disease, dropping to about 30% in later stages. In patients at intermediate or advanced stages of their disease an alkylating agent such as chlorambucil (with or without corticosteroids), cyclophosphamide or fludarabine (currently unlicensed in this indication) has been used as a first-line treatment.
When patients relapse or fail to respond to one of the first-line treatments (usually chlorambucil or, occasionally, cyclophosphamide), either combination treatment (such as CHOP, CAP or CVP) or fludarabine monotherapy is employed. A single cycle of combination therapy usually consists of drugs given by both the intravenous route (day 1) and orally (for a further 4 days). Cycles are repeated monthly for up to 6 months. Fludarabine is sometimes used as third-line treatment after combination therapy has failed.