Chronic myelomonocytic leukaemia (CMML) is a rare type of leukaemia (cancer of blood/blood forming tissue) that causes an overproduction of white blood cells (WBCs) in the blood and bone marrow. More specifically, it causes an overproduction of monocytes, which is the largest type of WBC in the blood that can develop into either a macrophage (ingest and degrade dead cells, debris, tumour cells and/or foreign substances) or a dendritic cell (initiate and regular the adaptive immune response).
Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps to remove waste from our bodies. There are three primary types of blood cells produced in the inner, spongy portion of the bone (bone marrow) from stem cells (immature blood cells that develop into either red blood cells (RBCs), white blood cells (WBCs), or platelets). RBCs, or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. WBCs are responsible for fighting infection and disease in the body. Platelets are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after injury.
CMML is classified as a mix of myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPN), as it shares characteristics of both. For more information on MDS or MPN, please refer to the Rare Cancers Australia Myelodysplastic Syndrome (MDS) page or the Myeloproliferative Neoplasms (MPN) page.
CMML is slightly more common in males, and tends to be diagnosed over the age of 70. However, anyone can develop this disease.
Types of Chronic Myelomonocytic Leukaemia
There are two types of CMML, which are characterised by the percentage of immature WBCs found in the blood and bone marrow.
Type 1 Chronic Myelomonocytic Leukaemia
Type 1 CMML is characterised by having between 2-4% of blasts (immature WBCs) in the blood and/or between 5-9% of blasts in the bone marrow. This subtype is characterised by the absence of Auer rods, which are long, needle-like structures that are present in abnormal cells under the microscope. Type 1 is not as aggressive as type 2 CMML, and can have a better prognosis than those with type 2 CMML.
Type 2 Chronic Myelomonocytic Leukaemia
Type 2 CMML is characterised by having between 5-19% of blasts in the blood and/or between 10-19% of blasts present in the bone marrow. Some patients with this subtype also have Auer rods present within the cancer cells, which are often indicative of aggressive disease behaviour. Type 2 CMML tends to be more aggressive than type 1 CMML, and may not have as good of a prognosis.
Transformation into Acute Myeloid Leukaemia
In some cases, CMML that has been left untreated can develop into acute myeloid leukaemia (AML), which is a rare type of leukaemia that causes an overproduction of myeloid cells (a specific type of dendritic cell) in the blood. For more information on CML, please refer to the Rare Cancers Australia Acute Myeloid Leukaemia (AML) page.
Treatment
When cancers are detected, they are staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, because of how rare CMMLs are, there is currently no standard staging and grading system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Whether your CMML is type 1 or type 2.
- Whether your CMML is more similar to an MDS or an MPN.
- Your symptoms.
- Your age.
- General health.
- Treatment preferences.
Your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. Your doctor will discuss the most appropriate course of treatment for you.
Treatment options for CMML may include:
- Watch and wait.
- Supportive treatment (treatment to improve your symptoms, quality of life, and delay transformation into AML), such as:
- Blood and platelet transfusions.
- Antibiotics.
- Chemotherapy.
- Stem cell transplants.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
While the cause of CMML remains unknown, some of the following factors may increase the likelihood of developing the disease:
- Genetic mutations, potentially including:
- TET 2 gene.
- RAS gene.
- ASXL1 gene.
- SRSF2 gene.
- Previous exposure to radiation therapy.
- Previous exposure to chemotherapy.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
CMML may appear asymptomatic during the early stages of disease. As the cancer progresses, some of the following symptoms may appear:
- Anaemia, with symptoms potentially including:
- Fatigue.
- Dizziness.
- Weakness.
- Shortness of breath.
- Paleness.
- Neutropenia, with symptoms potentially including:
- Recurrent infections.
- Fevers.
- Mouth ulcers.
- Thrombocytopenia, with symptoms potentially including:
- Easy bruising.
- Purpura or petechiae (a rash of small red dots due to small superficial capillary bleeds).
- Bleeding of the nose and/or the gums.
- Unexplained weight loss/loss of appetite.
- Fever.
- Night sweats.
- Fatigue.
- Frequent and/or persistent infections.
- Easy bleeding and/or bruising.
- Enlargement of the spleen (splenomegaly).
- Enlargement of the liver (hepatomegaly).
- Shortness of breath.
- Skin rashes and/or lumps.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have an CMML, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Blood tests
Blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Full blood count, which measures the levels of red blood cells, white blood cells and platelets.
- Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
- Blood smears to check changes in the number, type, shape, and size of blood cells for too much iron in RBCs.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-rays, ultrasounds, bone scans and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis.
Lumbar Puncture
A lumbar puncture, or spinal tap, involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis. A local anaesthetic or sedative is given prior to the procedure. Your doctor will discuss any risks and possible complications with you prior to the procedure.
Bone Marrow Aspiration & Biopsy
This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for abnormalities.
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells. This can be done by a fine needle aspiration (FNA), a core needle biopsy (CNB), or a trephine biopsy (removal of a small portion of bone for analysis).
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage CMML has a better prognosis and survival rates. However, if the cancer is advanced and has spread, or is found in adulthood, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.