Chronic Myelomonocytic Leukaemia (CMML)

Chronic myelomonocytic leukaemia (CMML) is a specific type of leukaemia which affects the myeloid-cell-producing stem cells.

Blood cells are formed in the bone marrow, which is a spongy tissue found inside the bones. Blood-forming stem cells divide to produce either more stem cells or immature cells that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. In CMML, the myeloid stem cells are affected.

A myeloid stem cell becomes one of three types of mature blood cells:

  • Red blood cells that carry oxygen and other substances to all tissues of the body.
  • Platelets that form blood clots to stop bleeding.
  • Granulocytes and monocytes (white blood cells) that fight infection and disease.

The characteristic feature of CMML is the presence of large numbers of a type of white blood cell called a monocyte.

Chronic myelomonocytic leukaemia (CMML) is a rare type of leukaemia characterised by increased levels of monocyte white blood cells, as well as features from the myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs).

MDS are a group of cancers where bone marrow cells of all types reproduce uncontrollably and have abnormal (dysplastic) changes. MDS are characterised by a poorly functioning bone marrow and a likelihood of progression to acute myeloid leukaemia (AML).

MPNs are a group of chronic disorders in which the myeloid stem cells in the bone marrow make too many abnormal red blood cells, white blood cells, or platelets. These abnormal cells do not function properly.

Despite having overlapping features with both MDS and MPNs, such as the overproduction of blood cells and the potential transformation to AML, CMML is still a distinct condition of its own. CMML is biologically different to MDS.

What causes CMML?

The exact cause of CMML is not known. However, it cannot be caught from someone or passed onto your children.

Known risk factors that increase the chances of getting CMML include:

  • Old age (60 years or older)
  • Being male
  • Being exposed to certain chemicals at work or in the environment
  • Past treatment with anticancer drugs and radiation
  • Having certain chromosome abnormalities and gene mutations

The origins of the CMML cells have been linked with the myeloid stem cells in the bone marrow. Bone marrow stem cells have the ability to develop into any type of blood cell. However, what makes the excessive reproduction of these monocytes derived from the myeloid stem cells is thought to be linked to genetic abnormalities.

Therapy-related CMML

Another cause of CMML, which accounts for about 10% of CMML cases, is thought to be receiving previous cancer treatment for a different cancer. This is known as therapy-related CMML. Therapy-related CMML is common after chemotherapy or radiation therapy. In comparison to CMML, therapy-related CMML patients have more complicated chromosome abnormalities and gene mutations. Therapy-related CMML is treated in the same way as other cases but does not respond as well to treatment.

Signs and symptoms

The most common symptoms of CMML are:

  • Fatigue
  • Anaemia
  • Breathlessness
  • Bruising and unusual bleeding
  • Loss of appetite and weight loss
  • Frequent, persistent infections
  • Sweating

It is uncommon to see effects of CMML outside the bone marrow; however, they may be in organs such as the spleen, liver, skin, and lymph nodes. This can result in the following symptoms:

  • Itching of the skin
  • Bone pain
  • Muscle pain
  • Enlarged lymph nodes
  • Fluid around the lungs (pleural effusion)
  • Enlarged spleen/liver (the enlargement may cause abdominal discomfort and, because the spleen lies next to the stomach, this enlargement may cause a feeling of early fullness when eating)

Diagnosis of CMML

For the majority of patients, a diagnosis of CMML can be made on the basis of a full blood count with a blood film and examination of a bone marrow sample. However, chromosome analysis and immunophenotyping are always carried out additionally to confirm the diagnosis, and to identify specific cases of CMML which are difficult to diagnose. They can also be useful in helping to rule out similar conditions and other types of leukaemia.

The 2016 World Health Organisation (WHO) requirements in order to make a diagnosis of CMML include:

  • Persistent increase (for at least three months) in high levels of monocytes equal or greater than 1.0 x 109/l, and a monocyte count greater than 10% of the white blood cells count.
  • Exclusion of the following conditions: other leukaemias with the Philadelphia chromosome fusion gene BCR-ABL1, classical MPN disorders or all other blood cancer that have increased levels of monocytes as a main feature.
  • CMML blast cells of up to 19% in either the blood or bone marrow, and exclusion of all other features of AML.

Three months or more of persistent increase in levels of blood monocytes is an important criteria which helps to differentiate CMML from an increase of monocytes resulting from an infection. In the case of an infection, the increase in monocytes returns to normal when the infection clears up.

The Philadelphia chromosome fusion gene BCR-ABL1 is an abnormal fusion gene due to a swapping over of sections of DNA between chromosome 9 (ABL1) and 11 (BCR). This gene causes the overproduction of myeloid cells. Having BCR-ABL1 means a patient is likely to have CML, which is a different type of leukaemia and is treated differently to CMML.

If the percentage of CMML blasts is 20% or more of the white blood cells in the blood or bone marrow, then a diagnosis of acute myeloid leukaemia (AML), which is a more aggressive form of leukaemia, should be made.

Classification of CMML

The new mutation-updated CPSS (CPSS-Mol) uses a point allocation system for the following four clinical factors to determine patient prognosis for overall survival time and incidence of patients progressing to AML.

These four factors are:

  • Genetic risk group
  • If the white blood cell count is equal to or greater than 13 x 109/L
  • If the percentage of bone marrow blasts is equal to or greater than 5%
  • If there is a need for red blood cell transfusions

The genetic risk score is then calculated using the original CPSS genetic score and the presence of mutations for the ASKL1, RUNX1, NRAS and SETBP1 genes.

Some people may want to know the survival statistics for patients with their type of cancer, whilst others may not find that useful or may not want to know. By using patients’ individual CPSS-Mol scores, they can be assigned to one of our risk groups: low, intermediate-1, intermediate-2 and high risk.

Staging of CMML

There is no staging in CMML, unlike in many forms of cancer. This is because CMML is spread throughout the body at the time of diagnosis.

There are systems for prognostic risk-scoring of CMML. These predict how well CMML is likely to respond to standard treatments and how likely it is to progress to AML. You can ask your specialist if you are interested in your risk score and what this means.

Treatment options

For most patients, CMML is treatable, but, as yet, it cannot be cured. However, it must be noted that many patients can lead a normal, good quality life while managing their CMML. This includes patients who might not need any active treatment and are under an approach called watch and wait, or active monitoring.

Once they have symptoms and need treatment, most patients with CMML are treated with chemotherapy, the most commonly used being hydroxycarbamide (sometimes referred to as hydroxyurea) and hypomethylating agents such as azacitidine. These drugs prevent DNA synthesis of proteins needed for growth of the CMML blast cells.

Patients may also receive treatment known as supportive treatment or palliative care. This helps to deal with complications from having low blood cell levels. It can involve red blood cell and platelet transfusions, and antibiotics to prevent and treat infections.


Although chemotherapy will not cure your CMML, it will help control your blood counts and disease and improve your quality of life. Chemotherapy is the use of drugs that work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them dividing. It is usually quite effective in helping to control CMML.

There are three groups of chemotherapy drugs that are used in treatment of CMML which are:

  • Hydroxycarbamide
  • Hypomethylating agents such as azacitidine
  • Conventional chemotherapy such as cytarabine

Stem cell transplants

Since chemotherapies cannot cure patients with CMML, SCTs are seen as the only potential cure, but the patients must be young and relatively fit to withstand the procedure. A SCT involves giving strong chemotherapy to kill off the cells in the bone marrow to prepare it for the transplant (also called conditioning) of healthy stem cells from a matched donor. The SCT helps re-establish a healthy bone marrow.

There is currently no evidence as to when is the best time for a SCT in CMML; however, expert recommendation based on clinical practice advises that a SCT should be performed in patients with CMML-2 or high-risk CMML.

Supportive treatment

Supportive treatment does not include active treatment, but it is given to maintain or improve the patient’s quality of life. It concentrates on treating any symptoms or complications that arise from the lack of normal blood cells which are features of CMML. The supportive care delivered will be adapted to the number of normal blood cells that are present in your blood.

Treatments for CMML, especially chemotherapies, destroy the CMML blast cells, but also most of the normal bone marrow cells. In patients with low-risk CMML and MDS features, anaemia can be treated with erythropoiesis stimulating agents to increase the production of red blood cells. For patients with proliferative features, administration of hydroxycarbamide remains the standard of care by preventing the multiplication of CMML blast cells which invade the bone marrow.

Blood transfusions may be needed if treatment with erythropoietin is unsuccessful, and platelet transfusions should be given if the platelet count level becomes too low. Chemotherapy treatment destroys CMML blast cells, but also most of normal bone marrow cells; therefore, patients may need antibiotics if they develop infections.

New treatments and treatments on the horizon

Your doctor may suggest you consider taking part in a trial of one of the new drugs. If this is the case, you will be given full information and a chance to ask questions. If you decide not to take part in a trial, you will receive the best available treatment.

Questions to ask your medical team about CMML

We understand going through a blood cancer through journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.

  • How would I know if I had CMML?
  • What tests will I need to have?
  • What will the tests show?
  • How long will the results take?
  • How rare is CMML?
  • What sort of treatment will I need?
  • How long will my treatment last?
  • What will the side effects be?
  • Is there anything I should or shouldn’t eat?
  • Will I be able to go back to work?
  • Where can I get help with claiming benefits and grants?
  • Where can I get help dealing with my feelings?

Further downloads

We have free patient information available for CMML patients.

You can download the booklets on our information pages here.

Alternatively, you can have the information delivered free of charge by requesting it through our resources page. 

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Published: July 2020

Review date: July 2023