Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 x 10(9)/L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in similar to 20-30% of patients, while >90% have gene mutations. Mutations involving TET2 (similar to 60%), SRSF2 (similar to 50%), ASXL1 (similar to 40%), and RAS (similar to 30%) are frequent; with only ASXL1 mutations negatively impacting overall survival. Two molecularly integrated, CMML-specific prognostic models include; the Groupe Franc, ais des Myelodysplasies (GFM) and the Molecular Mayo Model (MMM). The GFM model segregates patients into 3 groups based on: age >65 years, WBC >15 x 10(9)/L, anemia, platelets < 100 x 10(9)/L, and ASXL1 mutation status, with respective median survivals of 56 (low), 27.4 (intermediate), and 9.2 (high) months. The MMM is based on ASXL1 mutational status, absolute monocyte count >10 x 10(9)/L, hemoglobin < 10 g/dL, platelets < 100 x 10(9)/L and circulating immature myeloid cells. This model stratifies patients into four groups; high (similar to 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. Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of similar to 30-40% and complete remission rates of similar to 7-17%. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality. Individualized therapy, including epigenetic modifiers and small molecule inhibitors, are exciting prospects. (C) 2016 Wiley Periodicals, Inc.