{"id":356,"date":"2014-10-23T11:33:07","date_gmt":"2014-10-23T15:33:07","guid":{"rendered":"http:\/\/www.gqr-lmc-nmp.ca\/?page_id=356"},"modified":"2018-05-28T10:45:05","modified_gmt":"2018-05-28T14:45:05","slug":"chronic-myelogenous-leukemia-cml","status":"publish","type":"page","link":"https:\/\/www.gqr-lmc-nmp.ca\/system\/chronic-myelogenous-leukemia-cml\/?lang=en","title":{"rendered":"Chronic myeloid leukemia (CML)"},"content":{"rendered":"<ul>\n<li>Myeloproliferative neoplasm (blood cancer)<\/li>\n<li>New cases per year in Canada: 1-2 cases per 100 000 people per year (approx. 550 cases\/year in Canada)<\/li>\n<li>Median age at diagnostic: 45-55 years old<\/li>\n<\/ul>\n<h2><strong>Diagnostic:<\/strong><\/h2>\n<h4>Clinic:<\/h4>\n<ul>\n<li>Splenomegaly (increased volume of the spleen)<\/li>\n<li>Constitutional symptoms such as fatigue, fever, night sweats, anorexia and weight loss, anemia and recurring infections<\/li>\n<\/ul>\n<h4>Physiopathology (blood and bone marrow):<\/h4>\n<ul>\n<li>Increase leukocytes (granulocytosis)<\/li>\n<li>My\u00e9logramme avec cellularit\u00e9 riche et d\u00e9viation de la lign\u00e9e granulocytaire<\/li>\n<li>Presence of the Philadelphia&nbsp;chromosome resulting a hybrid <em>bcr\/abl<\/em> gene(Figure 1)<\/li>\n<\/ul>\n<figure id=\"attachment_143\" aria-labelledby=\"figcaption_attachment_143\" class=\"wp-caption alignnone\" style=\"width: 370px\"><a href=\"https:\/\/www.gqr-lmc-nmp.ca\/system\/system\/wp-content\/uploads\/2013\/07\/Chromosome-philadelphie.jpg\"><img decoding=\"async\" loading=\"lazy\" class=\"wp-image-143 size-medium\" title=\"Figure 1: Cr\u00e9ation du g\u00e8ne fusion bcr-abl par la translocation entre les chromosomes 9 et 22 dans la leuc\u00e9mie my\u00e9lo\u00efde chronique\" src=\"https:\/\/www.gqr-lmc-nmp.ca\/system\/system\/wp-content\/uploads\/2013\/07\/Chromosome-philadelphie-370x240.jpg\" alt=\"Chromosome philadelphie\" width=\"370\" height=\"240\" srcset=\"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-content\/uploads\/2013\/07\/Chromosome-philadelphie-370x240.jpg 370w, https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-content\/uploads\/2013\/07\/Chromosome-philadelphie-740x480.jpg 740w, https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-content\/uploads\/2013\/07\/Chromosome-philadelphie.jpg 840w\" sizes=\"(max-width: 370px) 100vw, 370px\" \/><\/a><figcaption id=\"figcaption_attachment_143\" class=\"wp-caption-text\">CML is the result of an acquired somatic mutation (the Philadelphia chromosome) that fuses, through reciprocal chromosomal translocation, the <em>bcr<\/em> and <em>abl<\/em> genes on chromosomes 22 and 9, respectively. the resulting gene codes for a fusion protein with tyrosine kinase activity.<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n<h2><strong>CML phases:<\/strong><\/h2>\n<h4>&nbsp;<a href=\"https:\/\/www.gqr-lmc-nmp.ca\/system\/system\/wp-content\/uploads\/2014\/10\/CML-phases-eng.jpg\"><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-477\" src=\"https:\/\/www.gqr-lmc-nmp.ca\/system\/system\/wp-content\/uploads\/2014\/10\/CML-phases-eng-370x173.jpg\" alt=\"CML phases eng\" width=\"577\" height=\"270\" srcset=\"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-content\/uploads\/2014\/10\/CML-phases-eng-370x173.jpg 370w, https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-content\/uploads\/2014\/10\/CML-phases-eng-740x347.jpg 740w, https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-content\/uploads\/2014\/10\/CML-phases-eng.jpg 1374w\" sizes=\"(max-width: 577px) 100vw, 577px\" \/><\/a><\/h4>\n<p>The initial CP of the disease, in which there may be no symptoms, presents in about 85% of patients with CML.&nbsp; Prior to recent treatment advances, the CP lasted 5-6 years, the AP 6-9 months, and the BC 3-6 months.<\/p>\n<h2><strong>CML treatment<br \/>\n<\/strong><\/h2>\n<p>Three approaches to treatment are known to exert a positive influence on the natural history of the disease:<\/p>\n<ol>\n<li>Allogeneic hematopoietic stem-cell transplantation (AHSCT)<\/li>\n<li>Interferon alpha (IFN-\u03b1) alone<a href=\"#_edn1\" name=\"_ednref1\"><\/a><sup><a href=\"#_edn2\" name=\"_ednref2\"><\/a><\/sup> or in combination with low-dose cytarabine<\/li>\n<li>Tyrosine kinase inhibitors (TKI)<\/li>\n<\/ol>\n<h3><strong>Stem-cell transplantation<\/strong><\/h3>\n<p>To this day, it is the only treatment that offers the only prospect for the cure of CML. In general, the best results are obtained in CP with approximately 80% long-term remission. Despite its effectiveness, only about 25% of CML patients are eligible for the procedure, owing to age restrictions, absence of suitable donors, and the higher incidence of graft-versus-host disease.<\/p>\n<h3><strong>Interferon alpha (IFN-\u03b1) <\/strong><\/h3>\n<p>Therapy with interferon alpha is most effective in early-phase CP-CML.&nbsp; Although IFN-a has expanded the therapeutic options for patients who are ineligible for transplant, the treatment has its shortcomings. Treatment for one or more years is required to establish the presence and degree of cytogenetic response, due to the slow kinetics of the biological response. For more than 50% of patients, side-effects related to IFN-a are intolerable and require dose reduction, while up to 25% discontinue treatment due to severe adverse effects.<\/p>\n<h3><strong>Tyrosine kinase inhibitors (TKI)<\/strong><\/h3>\n<div id=\"gt-res-content\" class=\"almost_half_cell\">\n<div dir=\"ltr\"><span lang=\"en\"><span lang=\"en\"><span lang=\"en\"><span class=\"hps\">The introduction of<\/span> <span class=\"hps alt-edited\">TKI<\/span> in <span class=\"hps\">2001<\/span> <span class=\"hps\">produces a<\/span> <span class=\"hps\">drastic change<\/span> <span class=\"hps\">in<\/span> <span class=\"hps\">the<\/span> <span class=\"hps\">clinical management<\/span> <span class=\"hps\">of CML. TKI inhibits the <em>bcr\/abl<\/em> tyrosine kinase and the proliferation of leukemic cells. Imatinib mesylate (Gleevec<sup>\u00ae<\/sup>), approved in first line by Health Canada in 2003, has profoundly altered the clinical and laboratory management of CML by becoming the standard of care and led the way to the development of more potent and selective second and third generation TKIs such as nilotinib (Tasigna<sup>\u00ae<\/sup>), dasatinib (Sprycel<sup>\u00ae<\/sup>),&nbsp;<\/span><\/span><\/span><\/span>bosutinib (Bosulif\u00ae) and ponatinib (Iclusig\u00ae).<\/p>\n<div>&nbsp;&nbsp;<\/div>\n<\/div>\n<\/div>\n<div>\n<h4><span id=\"result_box\" lang=\"en\"><span class=\"hps\">To help<\/span> <span class=\"hps\">hematologists<\/span> <span class=\"hps\">in their choice of<\/span> <span class=\"hps\">treatment options<\/span>, <span class=\"hps\">please<\/span> <span class=\"hps atn\">visit the &laquo;&nbsp;<a title=\"Guidelines\" href=\"\/?page_id=358&#038;lang=en\">T<\/a><\/span><a title=\"Guidelines\" href=\"\/?page_id=358&#038;lang=en\">reatment guidelines<\/a>&nbsp;&raquo; section <span class=\"hps\">to view<\/span> <span class=\"hps\">the recommendations<\/span> <span class=\"hps\">of the CML-MPN Quebec<\/span> <span class=\"hps\">Research Group<\/span><span class=\"hps\">.<\/span><\/span><\/h4>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Myeloproliferative neoplasm (blood cancer) New cases per year in Canada: 1-2 cases per 100 000 people per year (approx. 550\u2026<\/p>\n","protected":false},"author":4,"featured_media":0,"parent":0,"menu_order":50,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/pages\/356"}],"collection":[{"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/comments?post=356"}],"version-history":[{"count":8,"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/pages\/356\/revisions"}],"predecessor-version":[{"id":774,"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/pages\/356\/revisions\/774"}],"wp:attachment":[{"href":"https:\/\/www.gqr-lmc-nmp.ca\/system\/wp-json\/wp\/v2\/media?parent=356"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}