Chronic myelomonocytic leukemia diagnosis and management

• Published in: Leukemia 2021-06, Vol.35 (6), p.1552-1562
• Main Authors: Chan, Onyee, Renneville, Aline, Padron, Eric
• Format: Article
• Language: English
• Subjects: 692/699/1541/1990/1673; 692/699/1541/1990/2331; Abnormalities; Acute myeloid leukemia; Animals; Autoimmune diseases; Cancer Research; Care and treatment; Chromosome aberrations; Chronic myelomonocytic leukemia; Clinical trials; Combined Modality Therapy; Critical Care Medicine; Diagnosis; Disease Management; Evaluation; Hematology; Humans; Inflammation; Intensive; Internal Medicine; Leukemia; Leukemia, Myelomonocytic, Chronic - diagnosis; Leukemia, Myelomonocytic, Chronic - therapy; Life Sciences; Malignancy; Medical diagnosis; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Monocytes; Monocytosis; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Myeloid leukemia; Myelomonocytic leukemia; Oncology; Review Article; Risk; Risk groups; Signs and symptoms; Splenomegaly; Transplantation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-021-01207-3

Chronic myelomonocytic leukemia (CMML) is a rare, heterogeneous myeloid malignancy classified as a myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) overlap syndrome by the World Health Organization (WHO). Its initial presentation can be incidental or associated with myelodysplastic or myeloproliferative symptoms and up to 20% of patients harbor a concurrent inflammatory or autoimmune condition. Persistent monocytosis is the hallmark of CMML but diagnosis can be challenging. Increased understanding of human monocyte subsets, chromosomal abnormalities, and somatic gene mutations have led to more accurate diagnosis and improved prognostication. A number of risk stratification systems have been developed and validated but using those that incorporate molecular information such as CMML Prognostic Scoring System (CPSS)-Mol, Mayo Molecular, and Groupe Francophone des Myelodysplasies (GFM) are preferred. Symptom-directed approaches forms the basis of CMML management. Outcomes vary substantially depending on risk ranging from observation for a number of years to rapidly progressive disease and acute myeloid leukemia (AML) transformation. Patients who are low risk but with symptoms from cytopenias or proliferative features such as splenomegaly may be treated with hypomethylating agents (HMAs) or cytoreductive therapy, respectively, with the goal of durable symptoms control. Allogeneic hematopoietic cell transplantation should be considered for intermediate to high risk patients. The lack of effective pharmaceutical options has generated interest in novel therapeutics for this disease, and early phase clinical trial results are promising.