Three major staging systems exist for the classification of chronic lymphocytic leukemia. (These systems are described in TABLE.Common Staging Systems Used in the Treatment of Chronic Lymphocytic Leukemia).
The original Rai system, published in 1975, consists of stages 0-IV and is based on the presence of lymphadenopa-thy, organomegaly, and cytopenias, demonstrating a correlation between Rai stage and survival. This system was later modified from the five-tier system to a three-tier system that categorizes patients as having a low, intermediate, or high risk of disease progression.
TABLE.Common Staging Systems Used in the Treatment of Chronic Lymphocytic Leukemia
|Rai staging system||0||Lymphocytosis only|
|I||Lymphocytosis and lymphadenopathy|
|II||Lymphocytosis, spleen or liver enlargement|
|III||Lymphocytosis and anemia (hemoglobin <11 g/dL)|
|IV||Lymphocytosis and thrombocytopenia (platelet count < 100,000 mL)|
|Modified Raistaging system||Low risk ofprogression||Rai stage 0|
|Intermediate risk ofprogression||Rai stage I or II|
|High risk ofprogression||Rai stage III or IV|
|Binet stagingsystem||A||Lymphocytosis, with enlargement of <3lymphoid areas3; no anemia or thrombocytopenia|
|B||Lymphocytosis, with enlargement <3 lymphoid areas|
|C||Lymphocytosis and either anemia (hemoglobin <10 g/dL) or thrombocytopenia (platelet count <100,000/mL), or both|
a. The following lymphoid areas are included: cervical, axillary, inguinal (whether unilateral or bilateral), spleen, and liver.
The Binet classification system (A, B, C) was devised based on a retrospective analysis of disease burden that draws a correlation between the number of nodal groups involved with disease and bone marrow failure. The National Cancer Institute (NCI)’s guidelines for chronic lymphocytic leukemia state that the major distinctions and benefits of the Binet system derive from its recognition that (1) a predominantly splenic form of the disease may have a better prognosis in the Binet system than in the Rai systems, (2) patients with comorbid anemia or thrombocytopenia have a similar prognosis, and (3) the presence of either of these two conditions can be grouped in the same stage rather than in separate stages.
Although both the Rai and Binet systems group patients according to their risk of progression, the early stages of disease do not correspond well between the two systems. Binet’s good prognosis group, A, includes twice as many patients as Rai’s stage 0 because it includes all Rai stage 0, two-thirds of Rai stage I, and one-third of Rai stage II. The original and modified Rai systems are used throughout the United States; all three systems are used in Europe, although physicians quote Binet more frequently. The overlap among staging systems has made the comparison of clinical trials using different staging systems difficult.
Although the Rai and Binet staging systems each give general indications as to a patient’s prognosis, survival within each stage can vary significantly, particularly in those patients with Binet stage A and Rai stage 0. As many as 30% of these patients have “smoldering” chronic lymphocytic leukemia, which progresses slowly and never requires therapy; other patients have more progressive disease that will eventually require treatment and may be fatal. The median survival of patients with Rai stage 0 exceeds 12 years and may reach 20 years with a 10-year overall survival rate of 70-75%. Patients with Rai stage I and II have a median survival of 8-10 years and 5-8 years, respectively, whereas recent data show a median survival of 5 years and longer in Rai stage III and IV patients.