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      Evolution particulière de variants cytogénétiques complexes de leucémies myéloïdes chroniques traitées par l'Imatinib Translated title: Particular evolution of complex cytogenetic variants of chronic myeloid leukemia treated with imatinib

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          Abstract

          Les variants cytogénétiques simples et complexes constituent 5 à 10% de tous les cas de leucémie myéloïde chronique. Le mécanisme de leur formation a été proposé par certains auteurs. Les aspects clinique, thérapeutique et pronostique ne sont pas différents des formes classiques à l'aire des anti-tyrosines kinases. Nous rapportons deux cas traités par Imatinib dont l'évolution cytogénétique a été particulière. Les deux patients ont été inclus dans le programme GIPAP après signature d'un consentement éclairé. Chaque patient a bénéficié d'un examen clinique, d'un hémogramme, d'un myélogramme, d'un caryotype et ou d'une hybridation intra-génique avec fluorescence avant inclusion dans le programme. Chaque patient après inclusion a été traité avec l'Imatinib à la dose quotidienne de 400mg. La surveillance clinique, hématologique et cytogénétique et moléculaire a été faite selon les recommandations de LeukemiaNet.

          Most cited references9

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          Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.

          The introduction of imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML). Although experience is too limited to permit evidence-based evaluation of survival, the available data fully justify critical reassessment of CML management. The panel therefore reviewed treatment of CML since 1998. It confirmed the value of IM (400 mg/day) and of conventional allogeneic hematopoietic stem cell transplantation (alloHSCT). It recommended that the preferred initial treatment for most patients newly diagnosed in chronic phase should now be 400 mg IM daily. A dose increase of IM, alloHSCT, or investigational treatments were recommended in case of failure, and could be considered in case of suboptimal response. Failure was defined at 3 months (no hematologic response [HR]), 6 months (incomplete HR or no cytogenetic response [CgR]), 12 months (less than partial CgR [Philadelphia chromosome-positive (Ph(+)) > 35%]), 18 months (less than complete CgR), and in case of HR or CgR loss, or appearance of highly IM-resistant BCR-ABL mutations. Suboptimal response was defined at 3 months (incomplete HR), 6 months (less than partial CgR), 12 months (less than complete CgR), 18 months (less than major molecular response [MMolR]), and, in case of MMolR loss, other mutations or other chromosomal abnormalities. The importance of regular monitoring at experienced centers was highlighted.
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            Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis.

            Variant Philadelphia (Ph) chromosome translocations have been reported in 5%-10% of patients with newly diagnosed chronic myeloid leukemia (CML). Variant translocations may involve one or more chromosomes in addition to 9 and 22, and can be generated by 2 different mechanisms, 1-step and 2-step rearrangements, as revealed by fluorescence in situ hybridization. The prognostic significance of the occurrence of variant translocations has been discussed in previous studies. The European LeukemiaNet recommendations do not provide a "warning" for patients with variant translocations, but there is limited information about their outcome after therapy with tyrosine kinase inhibitors. To identify the role of variant translocations in early chronic phase (CP) CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective imatinib trials of the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Working Party on CML. Variant translocations occurred in 30 patients (5%). Our data show that the presence of variant translocations has no impact on the cytogenetic and molecular response or on outcome, regardless of the involvement of different mechanisms, the number of involved chromosomes, or the presence of deletions. Therefore, we suggest that patients with variant translocations do not constitute a "warning" category in the imatinib era. This study is registered at www.clinicaltrials.gov as NCT00514488 and NCT00510926.
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              Complex translocations, simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia.

              J Huret (1990)
              A proportion of cases of chronic myelogenous leukaemia (CML) has been described either (1) with a variant translocation, or (2) without the apparent involvement of both 9q34 and 22q11 (Ph-negative CML). All variant translocations have been further demonstrated to be complex implicating 9q34,22q11, plus another breakpoint on a variable chromosome. Complex translocations may be due to two successive events. Some of the breakpoints on the variable chromosome appear to be recurrent, and these remain to be studied for prognostic significance. Ph-negative CML comprises (1) cases of submicroscopic (hidden) insertion of 9q34-ABL within 22q11-BCR, and (2) cases without BCR-ABL rearrangement. We propose this last category to be called "CML-like disease", not to be confused anymore with true CML, and consequently to be studied as a separate entity.
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                Author and article information

                Journal
                Pan Afr Med J
                Pan Afr Med J
                PAMJ
                The Pan African Medical Journal
                The African Field Epidemiology Network
                1937-8688
                11 August 2013
                2013
                : 15
                : 132
                Affiliations
                [1 ]Laboratoire d'hématologie et d'immunologie Centre Hospitalier Universitaire Sourô Sanou 01 BP 676 Bobo Dioulasso 01, Burkina Faso
                [2 ]Médecine interne Centre Hospitalier Universitaire Sourô Sanou 01 BP 676 Bobo Dioulasso 01, Burkina Faso
                [3 ]Stomatologie Centre Hospitalier Universitaire Sourô Sanou 01 BP 676 Bobo Dioulasso 01, Burkina Faso
                [4 ]Centre International de Recherche pour le Développement de l'Elevage en zone Subhumide 01BP 454 Bobo Dioulasso 01, Burkina Faso
                [5 ]Laboratoire de Recherche en Sciences de la Santé et en Biotechnologie Animale, Institut du Développement Rural, Université Polytechnique de Bobo Dioulasso 01BP 1091 Bobo Dioulasso 01, Burkina Faso
                Author notes
                [& ]Corresponding author: Sawadogo Salifo, 01BP 676 service d'hématologie et d'immunologie. CHU Sourô Sanou, Bobo Dioulasso 01, Burkina Faso
                Article
                PAMJ-15-132
                10.11604/pamj.2013.15.132.2207
                3852512
                24319522
                2c679f30-c138-4894-a009-c01e262cca36
                © Sawadogo Salifo et al.

                The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 November 2012
                : 21 July 2013
                Categories
                Case Report

                Medicine
                leucémie myéloïde chronique,complexe variant,évolution cytogénétique,chronic myeloid leukemia,complex variant,cytogenetic evolution

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