Chronic myelomonocytic leukemia (ORPHA:98823)
A rare myelodysplastic/myeloproliferative neoplasm characterized by a spectrum of clinical, hematological, and morphological features, ranging from predominantly myelodysplastic to mainly myeloproliferative in nature, with blood monocytosis (> 1G/L, constituting > 10% of circulating leukocytes). Is it often associated with blood cytopenia and/or ''proliferative features'' (increased leukocyte counts, splenomegaly), with marrow dysplasia and risk of progression to acute myeloid leukemia (AML).
Epidemiology
The global annual incidence is approximately 1/147,000 with an important male predominance. The median age at diagnosis is 70.
Clinical description
The clinical symptoms are a consequence of blood cytopenias, mainly anemia (e.g. fatigue, dyspnea, possible angina, etc.), and less often of thrombocytopenia (spontaneous bleeding) or myeloproliferation (splenomegaly, serous effusions, and other nonspecific symptoms). The disease is associated with a 30% risk of transformation into AML.
Etiology
The etiology is unknown in 90% of the cases. It has acquired causes for the remaining 10%, including previous treatment with chemotherapy or radiotherapy, and occupational exposure to benzene derivatives or ionizing radiation. Marrow cell analysis by NGS method shows at least one somatic myeloid-lineage associated mutation in 90% of the cases, especially epigenetic (TET2, ASXL1, IDH), spliceosome (SRSF2) or other genes mutations (RUNX, NRAS or KRAS).
Diagnostic methods
The diagnosis is based on the following features: 1) Blood count reveals persistent monocytosis (>1G/L of circulating monocytes) with monocytes representing >10% of leukocytes (with or without increased leukocytes to >10G/L) and ''myelemia'' (myelocytes, metamylocytes) with or without cytopenias: anemia, aregenerative and often macrocytic, with or without thrombocytopenia. Infiltration of the liver, spleen, lymph nodes, and other organs is common. 2) Bone marrow morphology (from aspirate or biopsy) is generally hypercellular, with dysplasia in one to three myeloid lineages, without (<5%) or with (5-20%) excess blasts, and usually monocytosis. 3) Immunophenotyping of circulating monocytes reveals >94% of classical monocytes (MO1, CD14++/CD16−). 4) Bone marrow cytogenetics reveals acquired clonal abnormality in 30 % of the cases, especially chromosome loss (-7) or gain (+8). 5) NGS analysis reveals somatic mutation(s) in > 90% of the cases, especially TET2, SRSF2, ASXL1, RUNX1, NRAS or KRAS, while TP53 mutations are rare.
Differential diagnosis
The differential diagnosis mainly includes typical or atypical chronic myeloid leukemia (CML).
Management and treatment
Management and treatment of patients depends on their risk stratification level (of progression into AML). High risk CMML patients should have allogeneic bone marrow transplantation when possible, and otherwise hypomethylating agent-based treatment (azacytidine, decitabine). Lower risk CMML patients need treatment of their anemia with erythropoietin or derivatives. Myeloproliferation is treated by hydroxyurea, and thrombocytopenia (which often has a peripheral component) by the usual treatments used in peripheral thrombocytopenia.
Prognosis
Prognosis depends on the types and importance of cytopenias, the marrow blast percentage, marrow cytogenetic abnormalities, proliferative features (mainly leukocyte count) and somatic mutations, accounted for in a CMML prognostic scoring system (CPSS) which separates patients into low and high risk of progression into AML.

                            Last update: 
                            July 2023


                            - Expert reviewer(s): 
                            Pr Pierre FENAUX | EuroBloodNet*


                                * European Reference Network