How I diagnose and treat chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative overlap neoplasm characterized by sustained peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia (AML; 15-30% over 3-5 years). While CMML is morphologically classified in CMML-0,1 and 2 based on peripheral blood and bone marrow promonocyte/blast counts, a more clinically relevant classification into dysplastic (dCMML) and proliferative (pCMML) subtypes, based on the presenting white blood cell count is helpful in prognostication and therapeutics. CMML is a neoplasm associated with aging, occurring on the background of clonal hematopoiesis, with TET2 and SRSF2 mutations being early initiating events. The subsequent acquisitions of ASXL1, RUNX1, SF3B1 and DNMT3A mutations usually give rise to dCMML, while ASXL1, JAK2V617F and RAS pathway mutations give rise to pCMML. Patients with pCMML have a more aggressive course with higher rates of AML transformation. Allogeneic stem cell transplant remains the only potential cure for CMML, however, given the advanced median age at presentation (73 years) and comorbidities, is an option to only a few affected patients (10%). While DNA methyltransferase inhibitors are approved for the management of CMML, the overall response rates are 40-50%, with true complete remission rates of