The five lymphoid areas are (1) cervical lymph nodes, (2) axillary lymph

nodes, (3) inguinofemoral lymph nodes, (4) spleen, and (5) liver.

groups (Rai stages 0-II) (Table 7-2). The three-stage modified Rai system remains the most widely used system in the United States, whereas the Binet system is commonly used in Europe.

Although many patients in the high-risk group (Rai stages III and IV; Binet stage C) have a progressive clinical course, the course of the disease is not uniform in the other risk groups. Patients in the low- and intermediate-risk groups (Rai stages 0-II, Binet stages A and B) may have an indolent disease course, which spans several years or even decades, or the course may be progressive and associated with a short survival time. Thus, identification of prognostic factors within early-stage disease is important. Several prognostic factors have been found to be associated with inferior survival in CLL.60,61 These include a short lymphocyte doubling time (less than 12 months),62 a diffuse pattern of bone marrow infiltration,25,26 advanced age and male gender,61 abnormal karyotype,63-66 high serum levels of P2-microglobulin,67,68 soluble CD23,69,70 and a CLL-PLL category.71,72 Newer prognostic factors in CLL include the mutational status of Ig genes and CD38 expression on CLL lymphocytes.73,74 A recent report suggested that IgV gene mutations within CLL lymphocytes correlates with a significantly longer survival.73 Although controversial, some investigators have suggested that mutated IgV genes correlate with low expression (less than 30 percent) of CD38 on CLL lymphocytes. Although this correlation may not be exact, data examining CD38 expression on CLL lymphocytes clearly show a strong correlation between increased expression and inferior survival.

In the low-risk group, several investigators have defined a "smoldering" group whose disease is unlikely to progress. Investigators from Spain noted that patients with low absolute lym phocyte counts (below 30 X 109/L), hemoglobin above 12g/dL, and a bone marrow biopsy showing a nondiffuse (interstitial or nodular) pattern of lymphoid infiltration had a survival similar to those of age- and sex-matched control subjects.75 Similarly, investigators from France found that patients with Binet stage A disease with hemoglobin above 12 g/dL and blood lymphocytosis below 30 X 109/L had a survival time equal to that of an age-and sex-matched French population.76

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