The natural history of CLL is extremely variable, with survival times ranging from 2 to over 20 years from initial diagnosis. In 1975, Rai et al.56 proposed a staging system consisting of five stages (Rai 0 to IV) based on Dameshek's proposed model of orderly disease progression in CLL.57 The Rai stages were found to correlate with prognosis and were confirmed in numerous independent populations. This staging system is applicable to newly diagnosed and to previously treated patients, although the latter group has a less favorable prognosis. The Rai staging system was later modified58 into a three-stage system: low risk (Rai 0), intermediate risk (Rai I, II), and high risk (Rai III, IV). The actuarial survival curves according to the clinical stage at the time of diagnosis are shown in Figure 7-1. A similar staging system was developed in Europe by Binet et al.59; Binet stage C corresponds to the high-risk group (Rai stages III and IV), whereas Binet stages A and B correspond to the low- and intermediate-risk

Figure 7-1. Actual survival curves by Rai stage.

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