Prognosis and risk assessment in CMML. Prognostication for patients with CMML requires integration of diverse data. Adverse disease-specific factors incorporated into the new CPSS-Mol risk-stratification tool include a high white cell count (a marker of the proliferative capacity of the dominant hematopoietic clone), red cell transfusion dependency (a marker of the degree of marrow failure), increased marrow blast proportion, high risk karyotype, and somatic mutations in ASXL1, NRAS, SETBP1, or RUNX1. Other factors will also influence patient outcome, including older age, more severe comorbid conditions with poorer performance status, low socioeconomic status, poor access to high-quality health care, rapid disease progression, and failure to respond to therapy. It seems likely that additional factors that are currently more difficult to measure also influence clinical outcomes, such as the ability of the patient’s immune system to restrain clonal outgrowth, epigenetic patterns, the repertoire of aberrant splicing isoforms, or interactions of the clone with the marrow microenvironment.