{"id":5335,"date":"2021-05-15T23:53:42","date_gmt":"2021-05-15T21:53:42","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/hematology\/hematological-oncology\/chronic-myeloid-leukemia-cml\/"},"modified":"2022-02-06T23:13:46","modified_gmt":"2022-02-06T21:13:46","slug":"chronic-myeloid-leukemia-cml","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/oncological-disorders\/chronic-leukemias\/chronic-myeloid-leukemia-cml\/","title":{"rendered":"Chronic myeloid leukemia (CML)"},"content":{"rendered":"\n

Background<\/h3>\n<\/span>\n\n\n

In chronic leukemias, we see an accumulation of mature, mutated myeloid cells<\/strong>. The cells will undergo uncontrolled proliferation due to hyperactivated tyrosine kinases<\/strong> or other signaling pathway alterations.<\/p>\n\n\n\n

  • Chronic leukemias have a slow progression, and they can progress into acute leukemias (but not the other way around!)<\/li>
  • Incurable<\/li>
  • Mostly affect older patients.<\/li><\/ul>\n\n\n<\/span>\n

    Chronic myeloid leukemia<\/h3>\n<\/span>\n\n\n

    A clonal proliferation of pluripotent myeloid stem cells. <\/p>\n\n\n\n

    • Chronic <\/strong>= slow onset, of mature cells; myeloid<\/strong> = of the myeloid lineage; leukemia<\/strong> = cancer of the blood and bone marrow.<\/li>
    • Caused by t(9;22<\/strong>) Philadelphia chromosome<\/strong> (the abnormal chromosome 22 is the Ph chromosome), resulting in fusion of BCR-ABL1, where part of the oncogene ABL is moved next to BCR.
      • This results in the hyperactivation of the tyrosine kinase pathway.<\/li>
      • 10% of patients present without the presence of the Philadelphia chromosome, but with some BCR-ABL1 rearrangement, having the same consequences.<\/li>
      • A minority of CML patients present with no BCR-ABL1 disorders; this special case is classified under myeloproliferative diseases<\/strong>.<\/li><\/ul><\/li>
      • Compared with AML, the neoplastic cells are more mature (further along the differentiation cascade).<\/li>
      • Slow onset, can appear at any age.<\/li><\/ul>\n\n\n<\/span>\n

        Phases<\/h4>\n<\/span>\n\n\n

        The course of the disease is typically divided into 3 phases:<\/p>\n\n\n\n

        1. Chronic phase:<\/strong> <10% immature cells in the blood and bone marrow; most patients are diagnosed at this phase; responsive to therapy.<\/li>
        2. Accelerated phase:<\/strong> 10-20% immature cells; new cytogenic changes in addition to the BCR-ABL1; less responsive to therapy.<\/li>
        3. Blast phase:<\/strong> >20% immature cells; very bad prognosis; resistant to therapy.<\/li><\/ol>\n\n\n<\/span>\n

          Clinical presentation<\/h4>\n<\/span>\n\n\n
          • Asymptomatic in 30% of cases<\/li>
          • Weight loss, anorexia, night sweats<\/li>
          • Splenomegaly (always present, massive spleen; due to metastasis)<\/li>
          • Anemia and bleeding<\/li>
          • Gout (hyperuricemia)<\/li><\/ul>\n\n\n<\/span>\n

            Diagnosis<\/h4>\n<\/span>\n\n\n
            • Blood work (demonstrating leukocytosis >11G\/L leukocytes, increased basophil and eosinophil count, anemia)<\/li>
            • Chemistry (uric acid is increased)<\/li>
            • Blood smear (demonstrating myeloid precursors, e.g. band cells)<\/li>
            • GAPA or LAP (leukocyte alkaline phosphatase) score (a score reflecting the intracellular alkaline phosphatase activity of leukocytes; to measure it, 100 leukocytes are examined and scored 0-4; in CML, the GAPA is low)<\/li>
            • Bone marrow sample (hypercellular with granulopoiesis predominance)<\/li>
            • Genetic analysis (karyotyping, FISH, and PCR demonstrating Ph chromosome and BCR-ABL1 fusion)<\/li><\/ul>\n\n\n<\/span>\n

              Scoring system<\/h4>\n<\/span>\n\n\n

              There are several scoring systems available (e.g. Sokal<\/strong>, Hasford<\/strong>, and EUTOS<\/strong>), splitting the patients into low, intermediate, and high-risk. Most of them take into consideration the following parameters:<\/p>\n\n\n\n

              • Age of the patient<\/li>
              • The proportion of blast cells<\/li>
              • Spleen size<\/li>
              • Platelet count<\/li><\/ul>\n\n\n<\/span>\n

                Treatment<\/h4>\n<\/span>\n\n\n
                • TK-inhibitors (imatinib, nilotinib, dasatinib)
                  • Work by binding to the BCR-ABL1 tyrosine-kinase instead of ATP.<\/li>
                  • Ponatinib is a 3rd-gen TKi used in case of resistance<\/li><\/ul><\/li>
                  • Chemotherapy (hydroxycarbamide)<\/li>
                  • Stem cell transplantation<\/li><\/ul>\n<\/span>

                    Background<\/h3>

                    Chronic myeloid leukemia<\/h3>

                    Phases<\/h4>

                    Clinical presentation<\/h4>

                    Diagnosis<\/h4>

                    Scoring system<\/h4>

                    Treatment<\/h4><\/div>","protected":false},"excerpt":{"rendered":"

                    Background In chronic leukemias, we see an accumulation of mature, mutated myeloid cells. The cells will undergo uncontrolled proliferation due to hyperactivated tyrosine kinases or other signaling pathway alterations. Chronic leukemias have a slow progression, and they can progress into acute leukemias (but not the other way around!) Incurable Mostly affect older patients. Chronic myeloid leukemia A clonal proliferation […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":5474,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-5335","page","type-page","status-publish","hentry"],"yoast_head":"\nChronic myeloid leukemia (CML) – Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/oncological-disorders\/chronic-leukemias\/chronic-myeloid-leukemia-cml\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" 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