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Cytogenetic abnormalities occur in ~30% of patients, while &gt;95% harbor somatic mutations: <jats:italic>TET2<\/jats:italic> (~60%), <jats:italic>SRSF2<\/jats:italic> (~50%), <jats:italic>ASXL1<\/jats:italic> (~40%), <jats:italic>RAS<\/jats:italic> pathway (~30%), and others. The presence of <jats:italic>ASXL1<\/jats:italic> and <jats:italic>DNMT3A<\/jats:italic> mutations and absence of <jats:italic>TET2<\/jats:italic> mutations negatively impact overall survival (<jats:italic>ASXL1<\/jats:italic><jats:sup>WT<\/jats:sup>\/<jats:italic>TET2<\/jats:italic><jats:sup>MT<\/jats:sup> genotype being favorable).<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk Stratification<\/jats:title><jats:p>Several risk models serve similar purposes in identifying high\u2010risk patients that are considered for allogeneic stem cell transplant (ASCT) earlier than later. Risk factors in the Mayo Molecular Model (MMM) include presence of truncating <jats:italic>ASXL1<\/jats:italic> mutations, absolute monocyte count &gt;10\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L, hemoglobin &lt;10\u2009g\/dL, platelet count &lt;100\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L, and the presence of circulating immature myeloid cells; the resulting 4\u2010tiered risk categorization includes high (\u22653 risk factors), intermediate\u20102 (2 risk factors), intermediate\u20101 (1 risk factor), and low (no risk factors); the corresponding median survivals were 16, 31, 59, and 97\u2009months. CMML is also classified as being \u201cmyeloproliferative (MP\u2010CMML)\u201d or \u201cmyelodysplastic (MD\u2010CMML),\u201d based on the presence or absence of leukocyte count of \u226513\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L.<\/jats:p><\/jats:sec><jats:sec><jats:title>Treatment<\/jats:title><jats:p>ASCT is the only treatment modality that secures cure or long\u2010term survival and is appropriate for MMM high\/intermediate\u20102 risk disease. Drug therapy is currently not disease\u2010modifying and includes hydroxyurea and hypomethylating agents; a recent phase\u20103 study (DACOTA) comparing hydroxyurea and decitabine, in high\u2010risk MP\u2010CMML, showed similar overall survival at 23.1 versus 18.4\u2009months, respectively, despite response rates being higher for decitabine (56% vs. 31%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Unique Disease Associations<\/jats:title><jats:p>These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme\u2010induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.27271","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:17:54Z","timestamp":1709810274000},"page":"1142-1165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Chronic myelomonocytic leukemia: 2024 update on diagnosis, risk stratification and management"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-662X","authenticated-orcid":false,"given":"Mrinal M.","family":"Patnaik","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic  Rochester 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