Minimal residual disease assessment in chronic lymphocytic leukemia Volume 12, issue 4, Juillet-Août 2006


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Service d’hématologie biologique, hôpital Pitié-Salpêtrière, 47 boulevard de l’Hôpital, 75013 Paris

Chronic lymphocytic leukemia (CLL) has a variable course and a wide range of survival time from a few months to more than 25 years. New therapeutic approaches for the treatment of CLL lead to complete remission (CR) in a high rate of patients. However, relapse is ultimately observed in most of them. The duration of remission is correlated to the quality of the response. Thus, minimal residual disease (MRD) assessment is becoming critical for the treatment strategies and their monitoring in CLL. In the beginning of the nineties, MRD in CLL was evaluated by using classical molecular biology methods, i.e. southern blot, consensus IgH PCR and by single or dual color flow cytometry (FC). The implantation of new treatment modalities, such as application of monoclonal antibodies, and the better learning of the CLL B cells, allowed to develop novel techniques for MRD assessment in CLL. We and others, by using flow cytometry (FC) and molecular biology techniques, have shown that patients in CR with detectable MRD presented an increased risk for relapse, whereas those without detectable MRD experienced prolonged remission. Immunological marker analysis allows the detection of aberrant or unusual immunophenotypes, PCR techniques target clone-specific immunoglobulin gene rearrangements. Although clonotypic-PCR remains more sensitive (10 -5) than multicolor FC (10 -4), the latter is useful in routine practice for MRD evaluation and that phenotypic remission as well as molecular remission are associated with superior overall survival.