Chronic myelomonocytic leukemia (CMML) is a rare blood cancer of older adults in which the bone marrow makes too many monocytes, a type of white blood cell, while producing too few healthy red cells or platelets. Common symptoms are fatigue, an enlarged spleen, night sweats, weight loss, and easy bruising. Diagnosis rests on a persistently raised monocyte count plus a bone marrow biopsy, and treatment ranges from watchful monitoring to hypomethylating drugs and, for a small number of fit patients, a stem cell transplant.
Below I walk through what makes CMML unusual, the symptoms to look for, how it is diagnosed and classified, and the treatment strategies used today. For an overview of recent developments, see also our article on advances in chronic myelomonocytic leukemia diagnosis and management.
What Is Chronic Myelomonocytic Leukemia?
CMML is a hematological malignancy that sits between two families of marrow disorders. It is classified as a myelodysplastic/myeloproliferative neoplasm because it has features of both:
- Myelodysplastic features: abnormal-looking (dysplastic) cells and low blood counts, called cytopenias.
- Myeloproliferative features: overproduction of cells, especially monocytes, and often an enlarged spleen.
The disease starts in a stem cell within the bone marrow that acquires genetic changes and then produces an expanding clone of abnormal cells. It is most often diagnosed in people in their 70s and is more common in men.
How CMML Differs From Similar Leukemias
The name causes confusion with several other conditions:
| Condition | Key feature | How it differs from CMML |
|---|---|---|
| CMML | Persistent monocytosis, dysplasia, blasts under 20% | Chronic course; no BCR::ABL1 fusion |
| Chronic myelogenous leukemia (CML) | Philadelphia chromosome (BCR::ABL1) | Excess granulocytes, treated with tyrosine kinase inhibitors |
| Acute myelomonocytic leukemia | 20% or more blasts | An acute leukemia needing urgent treatment |
| Chronic lymphocytic leukemia (CLL) | Excess mature B lymphocytes | A lymphoid, not myeloid, cancer |
Causes and Risk Factors
In most people, CMML has no identifiable cause. It arises from acquired mutations in blood stem cells that build up with age; it is not inherited and not contagious. The genes most often affected are TET2, SRSF2, and ASXL1, along with genes in the RAS signaling pathway such as NRAS, KRAS, and CBL.
Recognized risk factors include older age, male sex, and previous chemotherapy or radiotherapy for another cancer. Smoking and certain chemical exposures are associated with myeloid cancers more generally.
Chronic Myelomonocytic Leukemia Symptoms
Some people have no symptoms, and CMML is found on a routine blood test. When symptoms occur, they fall into three groups.
From Low Blood Counts
- Fatigue, pallor, and breathlessness from anemia, because the marrow makes too few red blood cells.
- Easy bruising, nosebleeds, or bleeding gums from low platelets.
- Frequent or slow-to-clear infections, as the abnormal white cells do not work normally.
These reflect partial bone marrow failure.
From Cell Overproduction
- An enlarged spleen (splenomegaly), felt as fullness or discomfort under the left ribs or early satiety.
- An enlarged liver, and occasionally skin lesions or fluid around the lungs or heart.
General Symptoms
Night sweats, fevers without infection, and unintended weight loss are more common in the proliferative form of the disease.
How CMML Is Diagnosed
Diagnosis combines blood tests, a marrow examination, and genetic testing. Other causes of a high monocyte count, such as chronic infection or inflammation, must be excluded first.
| Test | What it shows |
|---|---|
| Complete blood count with differential | Persistent monocytosis: at least 0.5 × 10^9/L in current criteria (older criteria used 1 × 10^9/L), with monocytes making up at least 10% of white cells |
| Blood smear | Dysplastic cells and any circulating blasts |
| Bone marrow aspirate and biopsy | Cellularity, dysplasia, and blast percentage (must be under 20%) |
| Cytogenetics and gene sequencing | Chromosome changes and mutations such as TET2, SRSF2, ASXL1, RUNX1 |
| BCR::ABL1 testing | Must be negative to exclude CML |
| Flow cytometry | Abnormal monocyte subsets that support the diagnosis |
These tests pick up the hematological abnormalities that define the disease and rule out look-alikes.
Subtypes and Risk
CMML is divided by blast count into CMML-1 (fewer than 5% blasts in blood and fewer than 10% in marrow) and CMML-2 (5 to 19% in blood or 10 to 19% in marrow). It is also described as myelodysplastic type when the white count is below 13 × 10^9/L and myeloproliferative type when it is 13 × 10^9/L or higher. Doctors combine these with blood counts and mutations such as ASXL1 in dedicated CMML scoring systems to estimate prognosis and the risk of progression to acute leukemia.
Treatment Strategies for CMML
Treatment is tailored to symptoms, blood counts, risk category, age, and overall fitness. The goals are to control symptoms, improve blood counts, delay progression, and, where possible, cure.
- Watch and wait: lower-risk patients without symptoms may simply be monitored with regular blood counts.
- Supportive care: red cell and platelet transfusions, drugs to stimulate red cell production in selected patients, and prompt treatment of infections.
- Hydroxyurea: an oral drug used to lower a high white count and shrink an enlarged spleen in the proliferative form.
- Hypomethylating agents: azacitidine and decitabine, given in monthly cycles, can improve blood counts and control disease in higher-risk patients.
- Allogeneic stem cell transplantation: the only treatment that can cure CMML. It carries significant risks, so it is reserved for fitter patients, usually with higher-risk disease.
Clinical trials of targeted drugs are an option worth discussing, particularly for patients whose disease has specific mutations. You can read more in our overview of hematologic disorders.
Frequently Asked Questions
Is CMML a type of leukemia or MDS?
It is both, in a sense. CMML has “leukemia” in its name but is classified as an overlap myelodysplastic/myeloproliferative neoplasm, sharing features of MDS and of conditions that overproduce blood cells.
Can CMML turn into acute leukemia?
Yes, in some patients. When blasts reach 20% or more in the blood or marrow, the disease has transformed into acute myeloid leukemia. The risk is higher with CMML-2 and certain mutations.
Is CMML curable?
An allogeneic stem cell transplant is the only potentially curative treatment. For most patients, who are older, treatment aims at control and quality of life rather than cure.
What does a high monocyte count mean?
Most high monocyte counts are caused by infections, inflammation, or recovery after illness. CMML is considered only when the rise persists for at least three months and other causes have been excluded.
Key Takeaways
- CMML is a rare overlap blood cancer with persistent monocytosis and low counts of other cells.
- Chronic myelomonocytic leukemia symptoms include fatigue, bruising, infections, an enlarged spleen, night sweats, and weight loss.
- Diagnosis needs a persistent monocyte rise, a bone marrow biopsy, and genetic testing that excludes CML.
- Treatment strategies range from monitoring and hydroxyurea to hypomethylating agents and stem cell transplant.
- See your doctor if you have persistent fatigue, unexplained bruising, or left-sided abdominal fullness. More on related conditions is in our leukemia guide.
