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Prognosis factors in chronic lymphocytic leukemia. Appraisal and recommendations Volume 12, issue 5, Septembre-Octobre 2006

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Service d’hématologie clinique, CHU de Caen, av. George-Clemenceau, 14033 Caen

In chronic lymphocytic leukemia, prognostic factors have allowed a better classification of the disease outcome. This therefore has provided a more accurate stratification of patients in clinical trials. In the late 70’s, the Rai and Binet classifications both have proved to be highly predictive and widely applicable in clinical practice. These classifications have helped to separate prognostic subgroups and to identify patients for whom treatment may be deferred. However, they have demonstrated poor accuracy in the group of patients requiring active treatment. During the last decade, biological insights have dramatically improved our knowledge in the pathophysiology of the disease and in parallel have emerged as powerful prognostic indicators. Sequencing the gene of immunoglobulin heavy chain variable segments distinguish between patients with unmutated and mutated genes, two groups which markedly differ in overall survival. Additional findings using banding and FISH cytogenetics have identified a variety of genomic abnormalities of pronostic significance. Among them, del(17p), del(11q), complex abnormalities and translocations are poor prognosis indicators, whereas del(13q), as an isolated anomaly confers a better prognosis. Other biological features such as clonal B cells expression of ZAP-70 and/or CD38, high serum levels of thymidine kinase, soluble CD23, or β 2microglobulin, bone marrow infiltration pattern, lymphocyte doubling time, together with demographic characteristics like age and sex also display pronostic significance. Considering these factors is now of paramount importance for the design of specific clinical trials. However, their use for individual treatment decisions is not supported by the literature or expert opinions at this time as long as results of treatment trials won’t have demonstrated efficacy of prognostic-tailored regimens.