Chronic Myelomonocytic Leukaemia

Chronic myelomonocytic leukaemia (CMML) is a rare blood cancer where the bone marrow produces too many abnormal white blood cells called monocytes. This slow-growing condition affects mainly older adults and can cause fatigue, infections, and other complications as abnormal cells crowd out healthy blood cells.

Table of contents

• What is chronic myelomonocytic leukaemia?
• Who gets CMML?
• Causes and risk factors
• Signs and symptoms
• How doctors diagnose CMML
• Types and classification of CMML
• Treatment options
• Possible complications
• Living with CMML

What is chronic myelomonocytic leukaemia?

Chronic myelomonocytic leukaemia (CMML) is a rare type of blood cancer that affects how your body makes blood cells^[1]. To understand this condition, it helps to know that blood cells are made inside the bone marrow, which is the soft, spongy tissue found in the middle of some bones^[4].

In CMML, the bone marrow makes too many abnormal monocytes, a type of white blood cell that normally helps your body fight infection^[1]. These monocytes are not only too numerous but also abnormal and do not work as they should^[4]. As the number of abnormal blood cells increases, they take up space in the bone marrow and make it difficult for the bone marrow to produce other good quality mature blood cells such as red blood cells, platelets, and other white blood cells^[5].

Doctors classify CMML as a myeloproliferative neoplasm/myelodysplastic syndrome (MPN/MDS)^[1]. This means the condition has features of two different types of blood disorders. In myeloproliferative neoplasms, the bone marrow makes too many blood cells. In myelodysplastic syndromes, the bone marrow makes abnormal blood cells that are not fully mature^[1].

CMML is usually slow growing and develops over time. It can range on a spectrum from slow-growing to more aggressive^[1].

• Bone marrow
• Blood cells
• Spleen
• Liver

Who gets CMML?

CMML is a rare condition. Around 650 people are diagnosed with it each year in the UK^[6]. The exact incidence is difficult to define, but it is estimated to be approximately 1 in 100,000 people^[13].

This condition mainly affects older adults. The median age at diagnosis is between 70 and 75 years^[8]. A median is a midpoint, which means half of people diagnosed are younger and half are older than this age^[1].

CMML is more common in men than in women. Men are diagnosed about two times as often as women^[10].

While it can affect people of any age, CMML rarely affects children^[17].

Causes and risk factors

Researchers do not know the exact cause of CMML^[1]. The condition is not because of anything you have or have not done^[6]. However, scientists have identified several gene changes (also called mutations) that are associated with this condition^[1].

If you are diagnosed with CMML, you will likely have more than one mutation^[1]. Some of the most common gene changes involve the following genes: TET2 (found in about 60% of cases), SRSF2 (about 50%), ASXL1 (about 40%), and RAS pathway genes (about 30%)^[10].

Most of these genetic changes happen by chance during your lifetime. You did not get them from your parents and you cannot pass them to any children you have^[6].

Several factors can increase your risk of developing CMML:

• Age: Your risk increases as you get older, with most people diagnosed in their 70s^[1].
• Sex: More males are diagnosed than females^[1].
• Previous cancer treatment: About 1 in 10 people who develop CMML had previous cancer treatments like chemotherapy and radiation^[1]. When this happens, it is called therapy-related CMML^[6]. Healthcare providers carefully consider the risks of future cancers when they prescribe these treatments and only suggest them when the benefits clearly outweigh the risks^[1].

Signs and symptoms

CMML does not always cause symptoms at first^[1]. Sometimes you might not have symptoms when you are first diagnosed. You may be diagnosed after a blood test for something else^[6]. The first sign of chronic myelomonocytic leukaemia may be abnormal results on a routine blood test^[1].

When symptoms do appear, they usually develop gradually over time^[1]. The symptoms vary from person to person and might include:

• Feeling tired, breathless, or dizzy. This is a sign of anaemia, which means you have a low red blood cell count^[6].
• Fatigue or weakness that persists for no obvious reason^[1].
• Infections that last longer than expected or keep coming back. This happens because you have low levels of healthy white blood cells, a condition called neutropenia^[1].
• Excessive nosebleeds or bruising easily. This is a sign of thrombocytopenia, which means you have a low platelet count^[1].
• Tummy pain or bloating caused by an enlarged spleen^[6].
• Enlarged liver^[1].
• Unexplained weight loss^[1].
• Night sweats^[1].
• Bone pain^[1].
• Fever^[1].
• Skin rashes or lumps^[5].
• Aches and pains in your bones and muscles^[5].

How doctors diagnose CMML

Your healthcare provider will consider your symptoms and ask about your medical history^[1]. They will perform tests to check your blood cells.

The main tests include:

• Complete blood count: This blood test checks the number of different blood cells. A monocyte count that is too high (called monocytosis) may be a sign of CMML^[1].
• Peripheral blood smear: In this test, a sample of your blood is viewed under a microscope. Monocytes that look irregular or immature (called blast cells) may be a sign of CMML^[1].
• Bone marrow biopsy: Your provider may need to take a sample of bone marrow and test it in a lab to check for abnormal cells^[1].

The diagnosis of CMML is made using specific criteria. The newly revised diagnostic criteria include sustained (lasting more than 3 months) peripheral blood monocytosis. This means you have 0.5 × 10⁹/L or more monocytes in your blood, and monocytes make up 10% or more of your white blood cell count^[3].

Your doctor may also do tests on the bone marrow to look for changes in the chromosomes of the CMML cells. Chromosomes contain the genetic material inside cells. These tests are called cytogenetics^[11]. You might also have other tests done on the bone marrow to look for specific gene changes. This is sometimes called myeloid next generation sequencing^[11].

Types and classification of CMML

Doctors classify CMML into different types based on the number of blast cells found in your blood and bone marrow. The World Health Organization (WHO) separates CMML into two main subgroups^[5]:

• CMML-1: Less than 5% blast cells in blood and less than 10% in bone marrow^[5].
• CMML-2: Between 5-19% blast cells in blood and 10-19% in bone marrow^[5].

Doctors also classify CMML based on the number of white blood cells in your blood. This classification is more helpful for understanding how the disease might progress and what treatments might work best^[8]:

• Dysplastic CMML (dCMML): This type has fewer than 13,000 white blood cells per microliter in the blood. People with this type mainly have symptoms related to low blood cell counts, such as fatigue, bruising, and needing blood transfusions^[10].
• Proliferative CMML (pCMML): This type has 13,000 or more white blood cells per microliter in the blood. People with this type may have significant problems with too many blood cells, such as fever, weight loss, night sweats, and an enlarged spleen^[10].

Patients with proliferative CMML tend to have a more aggressive course with higher rates of transformation to acute myeloid leukaemia^[10].

Treatment options

For most people, CMML is treatable, but for most it is not curable^[11]. The type of treatment you need depends on the type of CMML you have, whether you have symptoms, your age, and whether you have any other medical conditions^[11].

Watchful waiting

If you have no or few symptoms, you might not need treatment at first^[11]. Instead, you will have regular check-ups including blood tests. You might hear this called watchful waiting or active monitoring^[11]. If your symptoms get worse or the disease progresses, you usually start treatment for CMML^[11].

Supportive treatment

Most people need supportive treatment at some point. The treatment you need depends on the type of symptoms you have^[11]:

• Blood and platelet transfusions: You might have blood transfusions if your red blood cells are low. If your platelets are low, you might require platelet transfusions, especially if you are experiencing any symptoms of bleeding^[11].
• Antibiotics: You might need to take antibiotics to treat infection and sometimes to prevent infection^[11].
• Growth factors: These are drugs that encourage your bone marrow to make more blood cells. Erythropoietin is a growth factor that increases the number of red blood cells. You might have this if your red blood cell level is low^[11].

Chemotherapy

Chemotherapy is a type of anti-cancer drug treatment. The drugs work by disrupting the growth of cells and stopping them from dividing^[11]. Chemotherapy treatments that are commonly used include:

• Azacitidine: This is a type of drug called a hypomethylating agent. It works by switching off a protein called DNA methyltransferase. This switches on genes that stop the cancer cells growing and dividing. You usually have azacitidine as an injection just under your skin given by your nurse^[11]. While DNA methyltransferase inhibitors are approved for the management of CMML, the overall response rates are 40-50%, with true complete remission rates of less than 20%^[10].
• Hydroxycarbamide (hydroxyurea): You might have hydroxycarbamide to help control a high white cell count^[11].

Stem cell transplant

Allogeneic stem cell transplant remains the only potential cure for CMML^[10]. In this treatment, you receive healthy stem cells from a donor to replace your diseased bone marrow. However, given the advanced median age at presentation (73 years) and other health conditions people may have, it is an option for only a few affected patients (about 10%)^[10].

Clinical trials

Your doctor may suggest taking part in a clinical trial if it is suitable for you^[1]. Clinical trials test new treatments to find out if they are safe and effective. Researchers are continuing to develop new drugs for CMML treatment and to prove their usefulness^[13].

Possible complications

In about 15-20% of cases (approximately 2 out of 10 cases), chronic myelomonocytic leukaemia transforms into acute myeloid leukaemia (AML) over 3-5 years^[3]. This happens when the number of blast cells in your blood increases above 20%^[17]. Ask your healthcare provider about your risk of developing AML based on your diagnosis and risk factors^[1].

Patients with proliferative CMML have a more aggressive course with higher rates of transformation to acute myeloid leukaemia^[8].

Living with CMML

Coping with a rare cancer can be difficult, both practically and emotionally^[16]. Being well informed about your condition and its treatment can help you to make decisions and cope with what happens^[16].

Taking in information can be difficult, especially when you have just been diagnosed. It can help to make a list of questions before you see your doctor. Take someone with you to remind you what you want to ask and help remember the answers^[16].

Ways to help yourself

The symptoms of CMML often mean that you feel less able to do everyday things. Talk to your doctor or nurse about any symptoms you have. There may be supportive treatments that can help you^[16]. You may also feel better if you:

• Eat a healthy, well-balanced diet^[16].
• Do some gentle exercise after checking with your doctor or nurse first^[16].
• Rest when you are tired^[16].

Try to work out your priorities each day if you get tired easily. Talk to your family and friends and ask for any help you need^[16].

Getting support

Talking to your friends and relatives about your CMML can help^[16]. It can also help to talk to people with the same condition. There are organizations that offer help and support, such as Blood Cancer UK and Leukaemia Care, which provide information, support groups, and helplines where you can talk to trained nurses and connect with other people affected by blood cancer^[16].

Learning about your condition can help you make decisions and feel more in control, but it is important to take things at your own pace and ask questions when you are ready^[18].