Chronic Myelomonocytic Leukaemia (CMML)

ChronicA long-lasting disease that changes slowly. myelomonocytic leukaemia (CMML) is a rare type of leukaemia (cancerA disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. Cancer cells can also spread to other parts of the body through the bloodstream and lymph systems. of bloodhello/blood forming tissue) that causes an overproduction of white blood cells
• the smallest, living parts of the body. Cells work together to form or build the body
• a human is made up of millions of Cells
• Cells reproduce themselves to make sure a body stays working
• sometimes Cells can be abnormal or damaged and these can be cancer cells
(WBCs) in the blood and bone marrowIs soft, spongy tissue found in bones that makes blood cells.. 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 plateletsSmall blood cells (shaped like plates) whose job it is to come together in a group(s) or clump(s) to stop bleeding when you are injured or cut.). 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 infectionWhere germs, bacteria or viruses that are not usually in the body, invade the body and make a person sick. 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 prognosisTo predict how a disease/condition may progress and what the outcome might be. 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 acutenew, recent, comes with an urgent or significant sense, is sudden, sharp or urgent 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, metastasisKnown as secondary cancer, it grows/spreads from the original/ primary cancer. (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
    • a chemical drug treatment to kill or slow-growing cancer Cells
    • these drugs are called cytotoxic drugs
    .
• Stem cell transplants.
• Clinical trials.
• Palliative careLessening pain without curing the disease..

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.

Symptoms

CMML may appear asymptomatic during the early stages of disease. As the cancer progresses, some of the following symptoms may appear:

• AnaemiaWhere the number of red blood cells have dropped. This can make people feel tired, breathless and unwell and affects how the body fights infection, with symptoms potentially including:
  • Fatigue.
  • Dizziness.
  • Weakness.
  • Shortness of breath.
  • Paleness.
• NeutropeniaWhen the number of neutrophils, a type of white blood cell, in your blood is too low and your body is less able to fight and kills germs and infection., 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 diagnosisUsing medical test results, identify and name a disease and/or condition., 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 assessTo measure, look at and learn from. overall health and detect any abnormalities. Some of these tests may include:

• General blood test to assess overall health.
• Full blood countA test that counts red blood cells, white blood cells and platelets in the blood., which measures the levels of red blood cells, white blood cells and platelets.
• Blood chemistry and/or blood hormoneA chemical made in different body parts/organs that is sent out to other parts of the body through the bloodstream. Hormones watch over and help control how other cells or organs act. 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 imagingTaking images/photos of inside body parts using magnet rather than x-ray. (MRITaking images/photos of inside body parts using magnet rather than x-ray.), a computed tomography scan (CT scanA 3-D (three dimensional) x-ray pictures that gives more information than a normal x-ray.), x-rays, ultrasounds, bone scans and/or positron emission tomography (PET scanA test that uses a radioactive drug to show a picture of how your tissues and organs are working. Also known as a positron emission tomography 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 anaestheticDrug given to stop pain and feeling to one body area only. 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 biopsyTo take a small piece of body tissue and test it in a laboratory. 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).

References

• Cancer Research UK
• Leukaemia Foundation
• UpToDate