CMML

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic neoplasm that lies at the intersection of myelodysplastic syndromes and myeloproliferative neoplasms. It is characterized by persistent monocytosis in the peripheral blood (usually defined as an absolute monocyte count of at least 1 x 10^9/L) and by dysplasia in one or more myeloid lineages. CMML is typically Philadelphia chromosome–negative, and by WHO criteria the blast percentage in blood and bone marrow remains below the threshold for acute leukemia. The disease is classified into subtypes (CMML-0, CMML-1, CMML-2) based on blast counts and the presence of Auer rods, reflecting increasing risk with higher blast levels.

Signs and symptoms can be variable. Common features include fatigue, dyspnea, infections due to neutropenia, bleeding from thrombocytopenia, and splenomegaly or hepatomegaly from extramedullary hematopoiesis. Some patients have leukocytosis with a monocytic predominance, while others present with cytopenias. CMML can progress to acute myeloid leukemia in a subset of patients.

Diagnosis involves a combination of laboratory and pathologic findings: persistent monocytosis, bone marrow and peripheral blood examination showing dysplasia, and exclusion of other myeloid neoplasms such as CML (BCR-ABL1 negative). Cytogenetic and molecular testing (including mutations in ASXL1, TET2, SRSF2, NRAS/KRAS and others) provide prognostic information.

Management focuses on symptom control and disease-modifying therapy. Hypomethylating agents (azacitidine or decitabine) are commonly used in higher-risk CMML. Hydroxyurea may manage leukocytosis or splenomegaly, and allogeneic stem cell transplantation remains the only potential curative option for eligible patients. Supportive care includes transfusions and antimicrobial treatment as needed. Prognosis varies with age, cytogenetics, and molecular abnormalities, with overall median survival measured in years and progression to acute leukemia in a subset of patients.