A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis

Abstract

Survivals of two series of CLL patients (99 from a retrospective series and 196 from a prospective series) were studied separately. The three main staging systems (Rai, Binet, Rundles) agreed well, but as far as survival is concerned, too many stages are defined. The authors performed a Cox multivariate analysis of survival in order to isolate important prognostic factors at diagnosis and to use them to build a simple three-stage classification. Thrombopenia and anemia appeared as the most important risk factors. Among the nonanemic and nonthrombopenic patients, the number of involved areas was clearly related to prognosis in the authors' two series. This study allowed the authors to propose a new classification in three prognostic groups. Group C: anemia (Hb less than 10 g) and/or thrombopenia (platelets less than 100,000/mm3); about 15% of the patients; median of 2 years. Group B: no anemia, no thrombopenia, three or more involved areas (counting as one each of the following: axillary, cervical, inguinal, lymph nodes, whether unilateral or bilateral, spleen and liver); about 30% of patients; median of 7 years. Group A: no anemia, no thrombopenia, less than three involved areas; about 55% of patients; the survival of this group does not seem different from that of the French population of the same age and sex distribution. This three-stage classification only requires clinical examination and routine hemogram, has a good prognostic value which was confirmed on the series of Montserrat and Rozman (146 patients), and should therefore be helpful in planning new clinical trials.

Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia

“…Eighty-one CLL Binet stage A (Binet et al, 1981) patients treated at our institution form the basis of this study. Their median age was 66 years (range, 44 -82 years) and the male to female ratio 49 to 32 years.…”

“…Furthermore, VEGF and b-FGF were investigated as predictor of clinical outcome. To this purpose we used as end-point disease-progression (DP) defined as the appearance of the upper stages according to the Binet (Binet et al, 1981) classification during the treatment-free period. As previously reported, DP has an important impact on overall survival of CLL patients in early disease stage (Molica, 1991).…”

“…In this study we expanded on previous observation by evaluating VEGF and b-FGF in the serum of patients with early CLL (i.e., Binet stage A) (Binet et al, 1981). In this subset of patients angiogenic cytokines were investigated as indicator of diseaseprogression (DP), an event which has an important impact on overall survival of CLL patients.…”

Autoimmune cytopenia does not predict poor prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma†

“…A modified Rai classification developed by the National Cancer Institute (NCI)-Sponsored Working Group in 1996 [12], also proposed that all CLL patients with anemia or thrombocytopenia should be considered to have high-risk disease. The Binet classification considers patients with a hgb level < 10 g/dl or a platelet count < 100 × 10 3 / l as having stage C disease [13]. Although the Rai and Binet classifications have helped greatly to advance clinical research and treatment of CLL patients, neither of these classifications makes allowance for an autoimmune etiology of the cytopenia.…”

Where is the causal variant? On the advantage of the family design over the case–control design in genetic association studies

“…However, the joint use of linkage and association information in families allows efficient designs for complex diseases. Using linkage information in association studies results not only in a gain of power in association testing, but also in an increased ability to estimate the risk conferred by the allelic variants, as illustrated in previous papers on Rheumatoid Arthritis 26,27 and MS. 7 The MASC method 28 was developed to exploit all information in family data. The association test from Perdry et al 4 is built on the same idea.…”