Chronic Myelomonocytic Leukemia (CMML)

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Chronic myelomonocytic leukemia, or CMML, is a cancer of the blood-forming cells that reside in the bone marrow. In CMML, the abnormalities in the blood-forming cells don’t just affect the bone marrow—they cause a person to have too many monocytes—a type of white blood cell—and this affects other parts of the body as well.


CMML stands for chronic myelomonocytic leukemia, while CML stands for chronic myeloid leukemia (also called chronic myelogenous leukemia). There can be similarities between CML and CMML in terms of the initial findings, but these two diseases are distinct.

Of the two, CMML generally carries a worse prognosis than CML, although many different factors can contribute to an individual’s prognosis and survival and there may be treatment therapies available depending on the individual case.

Causes and Risk Factors

CMML occurs mainly in older adults, often people who are above the age of 65.

In most cases of CMML, the cause is unknown, and there is no known way to prevent it. Some people develop CMML after receiving chemotherapy and radiation as part of their cancer treatment. In some cases, attempts can be made to avoid the chemotherapy drugs that are more likely to lead to CMML, but these drugs may be required, life-saving treatments in other cases.


The exact incidence of CMML is unknown. Overall, CMML is not a very common cancer; however, it is the most common type of blood disorder in its category, MDS/MPN, which is explained further below.


The classification of CMML, like that of many other blood cancers, has undergone some revision over the years, in parallel with the development of a better scientific understanding of the disease.

Today, CMML is recognized as having a blend of characteristics of two different categories of blood disorders: myelodysplastic syndrome and myeloproliferative neoplasm.

  • Myelodysplastic syndrome (MDS) is a group of diseases that affects normal blood cell production in the bone marrow. In MDS, the bone marrow produces abnormal-looking, immature blood cells called blast cells. These blast cells fail to mature properly and are unable to function in their intended roles as blood cells.
  • Myeloproliferative neoplasm (MPN) refers to diseases in which the bone marrow makes too many red blood cells, platelets, or different types of white blood cells.

People with CMML have abnormal-looking (dysplastic) cells in their bone marrow, and, so, for a long time, CMML was considered a type of myelodysplastic syndrome.

However, people with CMML also have an excess of monocyte white blood cells, and a key feature of MDS is having too few blood cells in the bloodstream, so CMML was never a really great fit for the category of MDS.

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

For these and other reasons, the World Health Organization (WHO) classification system includes CMML in a category all its own: MDS/MPN, as shown below.

CMML is one of several types of MDS/MPN.

  • Chronic myelomonocytic leukemia (CMML)
  • Atypical chronic myeloid leukemia (aCML), BCR-ABL1
  • Juvenile myelomonocytic leukemia (JMML)
  • MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)
  • MDS/MPN, unclassifiable

CMML is the most common disease in this group. Much less common diseases in this group are atypical chronic myeloid leukemia and juvenile myelomonocytic leukemia. All of these diseases produce a lot of abnormal blood cells.

In an update issued in 2016 by WHO, something formerly called refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) was introduced as a fully accepted, new diagnostic term, called MDS/MPN with ring sideroblasts and thrombocytosis.

Signs and Symptoms

Having too many monocytes over a prolonged period of time, generally, three months is the most common sign of CMML.

The excess of monocytes is to blame for many of the symptoms. The extra monocytes can travel and settle into to two organs in the abdomen, the liver, and the spleen, where they may cause enlargement and certain symptoms.

  • An enlarged spleen, or splenomegaly, can cause pain in the upper left part of the belly. Enlargement in this area can also cause people to feel full too fast when they eat.
  • If the liver becomes enlarged, which is called hepatomegaly, this may cause discomfort in the abdomen as well, in the upper right part.

Even though people with CMML make too many monocyte white blood cells, sometimes there can be a shortage of the other types of red and white cells as part of this whole process, and these shortages can also produce some of the symptoms of CMML.

  • A shortage of red blood cells, or anemia, can lead to feeling extremely tired, and also a weakness, shortness of breath, and pale skin.
  • Insufficient numbers of normal white blood cells, or leukopenia, can lead to frequent or severe infections.
  • A shortage of blood platelets, or thrombocytopenia, can lead to abnormal bleeding and bruising. In a person with CMML, this might be noticed as frequent or severe nosebleeds or bleeding gums.

Other symptoms may include unintentional weight loss, fever, and loss of appetite.

Signs and symptoms may offer clues, but they are not sufficient for a diagnosis of CMML.

Diagnosis and Evaluation

The diagnosis of CMML involves a specialized study of the cells from both your bloodstream and bone marrow. This means a bone marrow biopsy is part of the evaluation, in addition to the more familiar blood draw from a vein using a needle.

Based on the findings of initial testing, there is also a process of elimination that goes on, since many different illnesses can produce these symptoms and the very basic laboratory findings.

2016 WHO Criteria CMML Diagnosis

  • Persistent (more than 3 months) excess of monocytes (monocytosis) in the peripheral blood greater than 1000/microL.
  • Monocytes account for greater than 10 percent of the entire white blood cell (WBC) differential count.
  • Not meeting WHO criteria for other blood disorders: BCR-ABL1 positive chronic myeloid leukemia, primary myelofibrosis, polycythemia vera, or essential thrombocytosis
  • Percent of immature blast types in blood and marrow: less than 20 percent myeloblasts + monoblasts + promonocytes in peripheral blood and bone marrow.
  • Dysplastic changes (odd shapes and appearances under the microscope) in one or more families of developing blood cells in “the myeloid family tree.” In the myeloid family tree, the “branches” include cell lines that divide and mature to eventually produce monocytes, macrophages, neutrophils, basophils, eosinophils, red blood cells, dendritic cells, and megakaryocytes.

Diseases with findings similar to CMML often have to be ruled out, and sometimes doctors will perform additional tests recommended prior to treatment of patients with CMML, along with the initial workup, since they are already getting your bone marrow and blood samples for the diagnosis.

If certain genetic changes or rearrangements of certain genes are found in the problematic cells (uncommon in people with monocytosis, but include PDGFRA or PDGFRB, FGFR1, or PCM1-JAK2) then there is a different WHO classification given, and there are implications for treatment with a specific agent called imatinib.

CMML Categories

The WHO classification further categorizes people with CMML into three different categories that relate to the prognosis:

  • CMML-0: Less than 2 percent blasts in the peripheral blood and less than 5 percent blasts in the marrow.
  • CMML-1: 2 to 4 percent blasts in the peripheral blood and/or 5 to 9 percent blasts in the marrow.
  • CMML-2: 5 to 19 percent blasts in the peripheral blood, 10 to 19 percent blasts in the marrow, and/or presence of one or more Auer rods (clumps of burgundy colored granular material that form elongated shapes, seen in the cytoplasm of myeloid blasts).


A bone marrow transplant from a donor (allogeneic hematopoietic cell transplantation) is the only potentially curative treatment for patients with CMML. When it is an option, this decision is made as to the result of the doctor-patient discussion.

Clinical Trials

In terms of chemotherapy, so far, no “magic bullet for CMML” has yet been found. The treatments that are available do not greatly impact the natural progression of the disease, and so people with CMML are strongly encouraged to consider enrolling in clinical trials, when available.

For people who do not go for a transplant, and for those who do not enroll in a trial, there are several options for treating the illness, short of the cure, including symptom-directed therapy.

Symptom-Directed and Supportive Therapy

Expert guidelines say that patients without symptoms should be monitored by their doctors with periodic examinations and laboratory studies. They also recommend that immunizations be updated and if the patient is a smoker, that smoking is stopped.

In the absence of a clinical trial, there are still drugs available that may be used to “beat down” the excessive numbers of abnormal cells (cytoreductive therapy) such as hydroxyurea, azacitidine, or decitabine.

Supportive care for patients with CMML is similar to what is done for patients with MDS. Transfusions of red cells and platelets are often given, and the use of erythropoiesis-stimulating agents may be considered, as well as antibiotic treatment for infections.

For refractory CMML, or cases where treatments have been attempted but have failed, patients are encouraged to participate in clinical trials whenever they are available.


There is no good ballpark figure for survival, since people with CMML may have very different experiences with the disease.

A published median (or, statistically, the middle number in a series of survival times) is about 30 months survival from the time of diagnosis. There is wide variation in this median, however, and survival statistics, in general, do not reflect new treatments for which there is no data yet. Prognosis is considered in more detail below, once the different CMML risk groups are explained.

The uncertainty over statistics may make you feel anxious. An open conversation with your doctor will help you understand your individual case. There is a wide range of outcomes and survival times with CMML, and there are at least nine different scoring systems to try to help determine prognoses—systems that use things like clinical features and laboratory findings, and some also analyze the genetics of the cancerous cells.

There can be big differences in the way clinicians approach CMML risk, depending on the institution, but no data as yet seem to point to a single best way to assess risk.

Statistics from the American Cancer Society are now somewhat dated, however, they help to show differences by CMML-1 and CMML-2 categories, and they also illustrate how certain groups within the whole population seem to do better than others.

In one study of CMML patients diagnosed between 1975 and 2005, the median survival times with CMML-1 and CMML-2 were 20 months and 15 months, respectively. However, some patients lived much longer. About 20 percent of CMML-1 patients and about 10 percent of CMML-2 patients survived longer than five years. Also, patients with CMML-2 are more likely to go on to develop acute leukemia than patients with CMML-1. In the same study, 18 percent of CMML-1 patients and 63 percent of CMML-2 patients developed acute myeloid leukemia within five years of their CMML diagnosis.

A Word From Verywell

For the individual with CMML, the prognosis can depend on many different factors, and a person’s age and overall health are important ones. Because this disease tends to affect many older individuals who may have other chronic illnesses, the most aggressive treatment and one that is potentially curative—bone marrow transplant—is not always an option.

Good supportive measures are available, but CMML is a disease that seems to be on the edge of a needed therapeutic discovery. As such, what was printed yesterday may or may not be true tomorrow, so look at all of your options and consider enrolling in a clinical trial.

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