Chronic myelomonocytic leukemia: 2022 update on diagnosis, risk stratification, and management

Disease Overview: Chronic myelomonocytic leukemia (CM ML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (similar to 15% over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (<= 1 x 10(9)/L; monocytes >= 10%), usually with accompanying bone marrow dysplasia. Clonal cytogenetic abnormalities occur in similar to 30% of patients, while >90% have somatic gene mutations. Mutations involving TET2 (similar to 60%), SRSF2 (similar to 50%), ASXL1 (similar to 40%), and the oncogenic RAS pathway (similar to 30%) are frequent, while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact overall survival. Risk-Stratification: Molecularly integrated prognostic models include the Groupe Francais des Myelodysplasies, Mayo Molecular Model (MMM), and the CMML specific prognostic model. Risk factors incorporated into the MMM include presence of truncating ASXL1 mutations, absolute monocyte count >10 x 10(9)/L, hemoglobin <10 g/dL, platelet count <100 x 10(9)/L, and the presence of circulating immature myeloid cells. The MMM stratifies CM ML 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 similar to 40%-50% and complete remission rates of similar to 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.

Automated summary

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of peripheral blood monocytosis and bone marrow dysplasia. Mutations and risk factors affect prognosis, and hypomethylating agents are commonly used for treatment. Allogeneic stem cell transplant is a potential curative option.