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Chronic myelomonocytic leukemia: 2012 update on diagnosis, risk stratification, and management
Sameer A Parikh1, Ayalew Tefferi
1Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Insights
Chronic myelomonocytic leukemia (CMML) is a blood cancer defined by high monocyte counts. Diagnosis requires excluding other conditions, and risk stratification uses specific clinical and genetic factors for tailored therapy.
Area of Science:
- Hematology
- Oncology
- Stem Cell Biology
Background:
- Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm.
- Characterized by persistent absolute monocytosis (>1 × 10(9) L(-1)) in peripheral blood.
- Patients may experience cytopenias or hypercatabolic symptoms like night sweats and weight loss.
Purpose of the Study:
- To outline the diagnostic criteria for CMML.
- To discuss current risk stratification models for CMML.
- To review risk-adapted therapeutic options for CMML patients.
Main Methods:
- Diagnosis involves bone marrow morphology, histopathology, and chromosomal analysis, excluding other causes of monocytosis.
- Molecular abnormalities are common but not pathognomonic.
- Risk stratification considers bone marrow blasts, leukocyte count, hemoglobin, platelet count, and specific chromosomal abnormalities.
Main Results:
- No single pathognomonic finding for CMML diagnosis.
- Specific factors like bone marrow blasts ≥ 10%, leukocyte count ≥ 13 × 10(9) L(-1), and certain chromosomal abnormalities predict adverse survival.
- Azacitidine and decitabine are FDA-approved; novel agents and allogeneic stem cell transplant are under investigation.
Conclusions:
- CMML diagnosis requires comprehensive evaluation and exclusion of other conditions.
- Accurate risk stratification is crucial for guiding treatment decisions.
- Therapeutic strategies are evolving, including approved drugs, investigational agents, and stem cell transplantation.
Disease Overview:
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is classified as a myelodysplastic/myeloproliferative neoplasm by the 2008 World Health Organization classification of hematopoietic tumors. It is characterized by absolute monocytosis (>1 × 10(9) L(-1) ) in the peripheral blood that persists for at least 3 months. Patients may present with symptoms related to cytopenias and/or an underlying hypercatabolic state with drenching night sweats, splenomegaly, and weight loss.
Diagnosis:
The diagnosis of CMML rests on a combination of morphologic, histopathologic, and chromosomal abnormalities in the bone marrow, after careful exclusion of other conditions (both malignant and nonmalignant) that can cause monocytosis. Numerous molecular abnormalities have been recently recognized in patients with CMML-unfortunately, no single pathognomonic finding specific to CMML has been identified thus far.
Risk Stratification:
The International Prognostic Scoring System for myelodysplastic syndrome (MDS) cannot be used to risk stratify patients with CMML because this model excluded patients with a leukocyte count >12 × 10(9) L(-1) . Other risk stratification models such as the MD Anderson prognostic score and Dusseldorf score have been published. In the only model that took karyotype into account, bone marrow blasts ≥ 10%, leukocyte count ≥ 13 × 10(9) L(-1) , hemoglobin < 10 g/dL, platelet count < 100 × 10(9) L(-1) , and presence of trisomy 8, abnormalities of chromosome 7, or complex karyotype were found to be independent predictors of adverse survival.
Risk-Adapted Therapy:
The Food and Drug Administration has approved azacitidine and decitabine for the treatment of patients with CMML based on two pivotal trials in MDS. Novel classes of agents including immunomodulatory drugs, nucleoside analogs, and small-molecule tyrosine kinase inhibitors are being investigated in the treatment of CMML. With the advent of reduced intensity conditioning, an allogeneic stem cell transplant has also become a viable option for a subset of patients.
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