B-cell chronic lymphocytic leukemia (B-CLL), the most common form of leukemia in Western countries, results from the relentless accumulation of small, mature, slowly dividing, monoclonal B-lymphocytes (1). Affected patients are always adults: the median age at diagnosis is 64 yr. B-CLL cells are characterized by coexpression of the pan-B-cell markers CD5 and CD23, negativity for CD22 and FMC7 molecules, and low expression of the B-cell receptor surface Ig and Ig-associated molecule CD79b (2-4).
The possibility that genetic or familial factors may predispose to CLL is suggested by multiple reports of familial clustering, with first-degree relatives exhibiting a two- to sevenfold excess risk over the general population (5,6). Unlike acute leukemia and chronic granulocytic leukemia, CLL has not been associated with prior irradiation, and only a few reports suggest specific environmental predisposing factors (6). The low incidence of CLL among individuals of Japanese origin, including those who migrated to Hawaii, has been used to support the view that genetic influences play a stronger role than environmental factors in the pathogenesis of the disease (6). The nature of the genetic predisposition, however, remains unknown. No consistent chromosomal or proto-oncogene abnormality has been found in CLL, and the number of cases reporting common chromosomal and human lymphocyte antigen (HLA) phenotypes among affected siblings is small (1).
CLL is usually recognized first by the patient's primary care physician. Since the disease is far from uniform, decisions about therapy are often difficult. In addition, the mechanism of disease initiation and progression remains largely an enigma, and the growing characteristics of the clonal population result from an unbalanced complex of proliferation and apoptosis. In clinical terms, about one-third of patients never require treatment and have a long survival; in another third an initial indolent phase is followed by progression of the disease; and in the remaining have aggressive disease requiring immediate treatment is present at the outset.
The development of the Rai (7) and Binet (8) staging systems has allowed the division of CLL patients with into three prognostic groups: good, intermediate, and poor (Table 1). Binet's good prognosis group (stage A) includes twice as many patients as Rai's (stage 0), whereas the opposite applies to patients with an intermediate prognosis (Binet stage B or Rai stages I and II). These differences can affect the design of clinical trials.
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