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 effected.
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.
CMML has some similarities with a condition called myelodysplastic syndrome (MDS) and some resemblance to a group of conditions called myeloproliferative neoplasms (MPN). It is classified as being a mixture of these two conditions. About half of all cases have a high number of white cells at diagnosis and are most like MPN, while the remainder are more like MDS with low or normal white cell numbers at diagnosis. It is not clear whether these are separate diseases or different stages of the same disease.
CMML can be divided into two types, CMML-1 and CMML-2, based on the numbers of blasts in the blood and bone marrow and on the appearance of the blast cells. Treatment planning takes account of which type of CMML a patient has been diagnosed as having.
In a minority of cases CMML may develop into another form of leukaemia called acute myeloid leukaemia (AML). The distinction is based on the percentage of blast cells in the blood. This happens in between 15 and 30 in very 100 patients with CMML, and can happen after months or after years or even decades.
Myelomonocytic leukaemia rarely affects children, when this occurs it is regarded as a different disease to CMML, and is known as juvenile myelomonocytic leukaemia (JMML). This factsheet describes CMML, which affects adults only.
What causes CMML?
The cause of CMML is unknown but it is important to understand that:
- It is not a condition which can be caught from someone else (contagious)
- It is not passed on from a parent to a child (inherited)
- Age – like most forms of cancer, CMML is more common in older people
- Being male – CMML affects more males more than females
Signs and symptoms of CMML
There are no specific signs or symptoms which would allow a diagnosis of CMML to be made. The most common signs and symptoms are caused by the bone marrow being unable to produce enough normal blood cells.
- Anaemia – due to lack of red blood cells
- Weakness, tiredness, shortness of breath, light-headedness, palpitations
- Infections – due to lack of normal white blood cells
- Infections are more frequent, more severe and last longer
- Fever, malaise (general feeling of illness) and sweats
- Purpura (small bruises in skin), nosebleeds, bleeding gums
- Bleeding and bruising – due to lack of platelets
Other signs and symptoms which may occur include:
- Swollen spleen or liver, may occur in either type but is more common in the MPN type.
The defining feature of CMML is the presence of raised numbers of monocytes in the blood and bone marrow. Most patients with CMML will have bone marrow samples taken to confirm the diagnosis and to help to determine exactly what type of leukaemia a patient has. An important test in CMML looks for the absence of a specific abnormality in the chromosomes of the CMML cells. This is not an inherited genetic abnormality because it is not found in non-leukaemia cells. This is called the Philadelphia chromosome and indicates a different type of leukaemia called chronic myeloid leukaemia (CML).
Usually, a chest x-ray will be taken and also scans, to look for swollen lymph nodes, or other affected sites. Blood samples will be taken to test for any problems with the liver, kidneys or other organs. Some blood tests and scans will be repeated to check for the response to treatment and any complications. Other tests are usually only done at diagnosis.
Other tests which may be done include:
- X-rays, ultrasound or scans (CT or MRI) – To monitor impact on organs of the body.
Blood tests and bone marrow samples may be repeated during treatment to monitor response.
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 of CMML
The standard treatment for CMML is chemotherapy but, although this may help to control the disease, it may have unpleasant side effects, and is not a cure.
There are some drugs which may only work when specific genetic abnormalities are present. Stem cell transplantation is potentially curative, but is only suitable for a minority of patients.
You can find more information about drugs used to treat your CMML (and any other medicines you are taking) at the eMC Medicine Guides website: www.medicines.org.uk/emc/
Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. It is usually quite effective in helping to control CMML.
There are three main drugs used in treatment of CMML:
- Hydroxycarbamide (hydroxyurea)
- Cytarabine (ara-C)
- Azacitidine (although this is only given to those with the non-proliferative type of CMML-2)
Hydroxycarbamide and cytarabine are drugs that can kill abnormal cells and have been in use for some time to treat various blood cancers. These drugs are generally used when the CMML has more ‘myeloproliferative’ features, which means that the main problem is excess production of affected blood cells.
In other cases, which are more similar to a condition called myelodysplastic syndrome (MDS), the main problem is the production of abnormal blood cells that do not mature and work correctly. In this type of CMML, the main treatment used is azacitidine, which works in a different way. Azacitidine belongs to a class of drugs called ‘hypomethylating agents’ (HMA) and works by affecting the way in which the CMML cells switch genes on and off. Another HMA, called decitabine, is being studied to see if this gives better results than azacitidine.
In the small minority of CMML cases (less than 4%) where a certain genetic abnormality known as a ‘PDGFR fusion’ is present, a class of drugs called tyrosine kinase inhibitors (TKIs) may be very effective. The most commonly-used drug in this class is imatinib. These drugs have been in use for some years to treat another disease called chronic myeloid leukaemia (CML).
Your haematologist or clinical nurse specialist will explain the possible side effects, advantages and potential disadvantages of any chemotherapy treatment.
Stem cell transplant
For younger patients with high-risk features, a stem cell transplant may be recommended. This means having chemotherapy to kill off the bone marrow followed by a transplant of healthy stem cells from a matched donor. There are two types of donor transplant which can be done.
For fitter or younger patients, a type called a myeloablative transplant uses very strong doses of chemotherapy and radiotherapy. This has the advantage of minimising the risk of the CMML returning (a relapse), and may cure CMML, but is very toxic. People who respond better to standard treatment are more likely to have a favourable outcome when they have a stem cell transplantation.
If a patient is well enough to have a transplant, but not fit enough for myeloablative transplant, a procedure called reduced intensity conditioning (RIC) transplant may be considered. A RIC transplant uses lower doses of pre-transplant chemotherapy (conditioning), which means that it is less dangerous but there may be a higher chance or relapse.
If you are being considered for a stem cell transplant, your haematologist will explain in detail what this will involve, and the possible risks and benefits.
New treatments and treatments on the horizon
There are several different types of new drugs being studied for possible use in CMML but, at present, these are in early stage trials and, except perhaps decitabine, are unlikely to be used routinely in the near future. Some of the drugs being studied are likely to be used only for specific groups of patients as they target genetic abnormalities that are not found in all CMML cells.
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?
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.
Published date: June 2018
Review date: June 2020