Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management

• Published in: American journal of hematology Vol. 95; no. 1; pp. 97 - 115
• Main Authors: Patnaik, Mrinal M., Tefferi, Ayalew
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-01-2020; Wiley Subscription Services, Inc
• Subjects: 5-aza-2'-deoxycytidine; Aged; Antimetabolites, Antineoplastic - therapeutic use; Bone dysplasia; Bone marrow; Chronic myelomonocytic leukemia; Cytogenetics; Diagnosis; Disease Management; Female; Frameshift mutation; Hematology; Hematopoietic stem cells; Hemoglobin; Humans; Leukemia; Leukemia, Myelomonocytic, Chronic - diagnosis; Leukemia, Myelomonocytic, Chronic - mortality; Leukemia, Myelomonocytic, Chronic - therapy; Male; Middle Aged; Molecular modelling; Monocytes; Monocytosis; Morbidity; Mutation; Myelodysplastic syndrome; Myeloid cells; Myelomonocytic leukemia; Peripheral blood; Remission; Remission Induction - methods; Risk Assessment; Risk factors; Stem Cell Transplantation - methods; Stem cells; Survival Analysis; Transplantation, Homologous
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.25684

Disease overview
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3‐5 years).
Diagnosis
Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109/L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over‐all survival.
Risk stratification
Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS‐Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate‐2 (2 risk factors), intermediate‐1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively.
Risk‐adapted therapy
Hypomethylating agents such as 5‐azacitidine and decitabine are commonly used, with overall response rates of ~40%‐50% and complete remission rates of ~7%‐17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.