Being told that you have chronic myelomonocytic leukaemia, usually shortened to CMML, can be confusing. The name is long, it sounds alarmingly similar to several other blood cancers, and an internet search tends to produce either incomprehensible genetics or survival statistics stripped of all human context. A magnificent system humanity has built.

CMML is a rare blood cancer that begins in the blood-forming stem cells of the bone marrow. It usually develops gradually, although its behaviour varies considerably between individuals. Some people require treatment soon after diagnosis, while others can be safely monitored for months or years.

Important: This article provides general information. Treatment decisions should be made with your haematology team, based on your blood results, bone marrow findings, symptoms, general health and personal priorities.

What does the bone marrow do?

Bone marrow is the soft tissue inside certain bones. It acts as the body’s blood-cell factory and normally produces:

  • Red blood cells, which carry oxygen
  • White blood cells, which help fight infection
  • Platelets, which help stop bleeding

All these cells develop from blood-forming stem cells. In CMML, one of these stem cells acquires genetic changes and begins producing abnormal blood cells, particularly cells belonging to the monocyte family.

What are monocytes?

Monocytes are a type of white blood cell. They circulate in the bloodstream and help the immune system respond to infection, inflammation and damaged tissue.

In CMML, the bone marrow produces a persistently increased number of abnormal monocytes. These cells may accumulate in the blood, bone marrow, spleen, liver and occasionally other tissues. At the same time, abnormal marrow function may reduce the production of normal red cells, platelets and other white cells.

Is CMML a leukaemia, MDS or MPN?

CMML has features of two groups of blood disorders:

Myelodysplastic neoplasms

In myelodysplastic neoplasms, often called MDS, the bone marrow produces abnormal or poorly functioning blood cells. This may lead to anaemia, low platelets or low neutrophils.

Myeloproliferative neoplasms

In myeloproliferative neoplasms, known as MPNs, the marrow produces excessive numbers of one or more types of blood cells. This may cause a high white-cell count or an enlarged spleen.

Because CMML can show both patterns, it is classified as an MDS/MPN overlap neoplasm. It is not the same condition as chronic myeloid leukaemia, or CML, despite the irritatingly similar abbreviations.

What causes CMML?

CMML develops when genetic changes occur in a blood-forming stem cell. These changes allow abnormal cells to survive and multiply.

For most people, there is no single identifiable cause. CMML is:

  • Not caused by something you ate
  • Not caused by emotional stress
  • Not contagious
  • Not inherited in the usual sense
  • Not something you caused through lifestyle choices

Previous chemotherapy or radiotherapy can occasionally contribute to the development of a related myeloid cancer, but most people with CMML have no obvious trigger.

Who develops CMML?

CMML mainly affects older adults and is more common in men than women. It is uncommon in younger adults and very rare in children.

What symptoms can CMML cause?

Some people have no symptoms when CMML is first discovered. The diagnosis may begin with an abnormal full blood count performed for an unrelated reason.

Symptoms depend on whether CMML is causing low blood counts, high white-cell counts, enlargement of the spleen or general inflammation.

Symptoms caused by anaemia

Too few red blood cells may cause:

  • Tiredness
  • Shortness of breath
  • Reduced exercise tolerance
  • Dizziness
  • Headaches
  • Paleness
  • A racing heartbeat

Symptoms caused by low platelets

Too few platelets may cause:

  • Easy bruising
  • Nosebleeds
  • Bleeding gums
  • Small red or purple spots under the skin
  • Prolonged bleeding from cuts

Symptoms caused by abnormal white blood cells

Abnormal marrow function may interfere with normal immunity and cause:

  • Frequent infections
  • Infections that are unusually severe
  • Slow recovery from infections
  • Fevers without an obvious infection

Symptoms caused by an enlarged spleen

Abnormal cells can collect in the spleen, causing:

  • Discomfort or pressure under the left ribs
  • Abdominal fullness
  • Feeling full after eating a small amount
  • Unexplained weight loss

Night sweats, fevers, bone discomfort and general loss of wellbeing can also occur, although these symptoms are not specific to CMML.

How is CMML diagnosed?

CMML can be difficult to diagnose because infections, inflammation, autoimmune diseases and some other cancers can also increase the monocyte count.

Diagnosis usually involves several parts.

Blood tests

A full blood count measures:

  • Monocytes
  • Total white-cell count
  • Haemoglobin
  • Platelets
  • Neutrophils
  • Immature blood cells, including blasts

Doctors generally need to establish that the monocytosis is persistent rather than a temporary reaction to infection or inflammation.

A blood film allows the cells to be examined under a microscope. The laboratory may identify abnormal monocytes, immature cells or changes affecting red cells and platelets.

Bone marrow examination

A bone marrow biopsy is usually taken from the back of the pelvic bone under local anaesthetic. It allows assessment of:

  • The number and appearance of marrow cells
  • The percentage of immature cells, called blasts
  • Abnormal maturation or dysplasia
  • Fibrosis or scarring
  • Chromosome changes
  • Gene mutations

The procedure is unpleasant rather than anyone’s preferred recreational activity, but it provides information that cannot reliably be obtained from blood tests alone.

Genetic and molecular testing

CMML cells often contain acquired mutations in genes involved in blood-cell development. Commonly tested genes include:

  • TET2
  • SRSF2
  • ASXL1
  • RUNX1
  • NRAS
  • KRAS
  • CBL
  • SETBP1

These mutations are not usually inherited from a parent. They developed within the abnormal marrow cells during the person’s lifetime.

Genetic results can help support the diagnosis, estimate the likely behaviour of the condition and guide decisions about treatment or transplantation.

Other tests are performed to exclude conditions that can resemble CMML. Diagnosis therefore often requires repeated blood tests, bone marrow assessment and exclusion of alternative causes.

Are there different types of CMML?

CMML is commonly described as either dysplastic or proliferative, based partly on the white-cell count.

Dysplastic CMML

The white-cell count is below 13 × 10⁹/L. Patients may be more affected by low haemoglobin, low platelets or other features resembling MDS.

Proliferative CMML

The white-cell count is 13 × 10⁹/L or higher. Patients may have:

  • A larger spleen
  • Constitutional symptoms
  • Increasing monocytes
  • Higher total white-cell counts
  • More features resembling an MPN

This distinction helps describe the disease but does not, by itself, determine treatment.

What are blasts?

Blasts are very immature blood-forming cells. Everyone has a small number of blasts in the bone marrow, but they are normally not present in significant numbers in the bloodstream.

An increased blast percentage can indicate more advanced CMML and a higher likelihood of transformation into acute myeloid leukaemia, or AML.

CMML is divided into categories based partly on the percentage of blasts in the blood and bone marrow. Your haematologist may also use a formal risk calculator that includes:

  • Age
  • Blood counts
  • Blast percentage
  • Chromosome findings
  • Gene mutations
  • Transfusion requirements
  • White-cell count

These systems estimate risk across groups of patients. They cannot predict exactly what will happen to one particular person.

Can CMML turn into acute leukaemia?

CMML can transform into AML. Across large patient groups, approximately 15% to 30% of people eventually develop AML. The risk is not the same for everyone and is influenced by blast percentage, blood counts, chromosome changes, mutations and how the disease behaves over time.

This does not mean that every person with CMML is inevitably progressing towards acute leukaemia. Some people live with relatively stable disease for a prolonged period.

Does everyone need treatment immediately?

No.

People with lower-risk CMML who feel well and have stable blood counts may be managed with active monitoring, sometimes called watchful waiting.

Monitoring may include:

  • Regular full blood counts
  • Review of symptoms
  • Examination of the spleen
  • Repeat bone marrow testing when clinically necessary
  • Monitoring for increasing blasts or worsening cytopenias

Observation does not mean the condition is being ignored. It means treatment is being reserved until its likely benefits outweigh its risks.

Treatment may be recommended when CMML causes:

  • Significant anaemia
  • Recurrent infections
  • Bleeding or very low platelets
  • Rapidly increasing white-cell counts
  • Painful or progressive spleen enlargement
  • Fevers, night sweats or weight loss
  • Increasing blasts
  • Progressive or higher-risk disease

How is CMML treated?

Treatment is individualised. Factors include:

  • Symptoms
  • Blood counts
  • Blast percentage
  • Genetic findings
  • Rate of progression
  • Age and general fitness
  • Other medical conditions
  • Suitability for transplantation
  • The patient’s preferences and quality of life

Drug treatments can often control CMML, improve blood counts and reduce symptoms, but they do not usually eliminate every abnormal stem cell.

Supportive treatment

Supportive care treats the consequences of CMML rather than directly attacking the abnormal clone.

It may include:

  • Red-cell transfusions for symptomatic anaemia
  • Platelet transfusions for severe thrombocytopenia or bleeding
  • Antibiotics for infection
  • Vaccinations where appropriate
  • Growth-factor treatment in selected patients
  • Iron-chelation therapy in a small number of heavily transfused patients
  • Nutritional and exercise support

Supportive care is genuine treatment, not a lesser substitute for “real” therapy.

Hydroxycarbamide

Hydroxycarbamide, also called hydroxyurea, can lower an excessive white-cell or monocyte count. It may reduce spleen size and improve symptoms in proliferative CMML.

It is taken as a capsule or tablet, with the dose adjusted according to blood counts.

Possible adverse effects include:

  • Lower blood counts
  • Mouth ulcers
  • Skin changes
  • Gastrointestinal upset
  • Leg ulcers with prolonged use in some patients

Hydroxycarbamide controls cell production but is not generally considered curative.

Azacitidine and decitabine

Azacitidine and decitabine are hypomethylating agents. They alter the way abnormal genes are switched on and off within marrow cells.

These treatments may:

  • Improve blood counts
  • Reduce transfusion needs
  • Reduce blasts
  • Improve spleen-related or constitutional symptoms
  • Delay disease progression in some patients

Responses often take several treatment cycles. Treatment can initially worsen blood counts, so patients require regular monitoring and may need transfusions or antibiotics.

Not every patient responds, and responses may not be permanent. These drugs can nevertheless provide meaningful control for some people.

Intensive chemotherapy

AML-style intensive chemotherapy is sometimes used when CMML has transformed into AML, when the blast count is very high, or as preparation for transplantation in selected patients.

It carries substantial risks, including:

  • Severe infections
  • Bleeding
  • Organ toxicity
  • Prolonged hospitalisation
  • Significant treatment-related mortality

It is therefore not routinely suitable for every person with CMML.

Clinical trials

Clinical trials may provide access to new treatments or combinations. Trials are particularly important in CMML because currently available treatments remain imperfect, a charitable description for a field where biology continues to outsmart pharmacology.

A trial may test:

  • New targeted drugs
  • Anti-inflammatory pathways
  • Mutation-directed therapies
  • New combinations with azacitidine
  • Treatments intended to improve transplant outcomes

Joining a trial is voluntary and should involve a detailed discussion of possible benefits, uncertainties and additional appointments or tests.

Can CMML be cured?

An allogeneic stem-cell transplant is currently the only treatment with established curative potential.

In this procedure, chemotherapy, sometimes combined with radiotherapy, is used to suppress or remove the patient’s abnormal marrow. Blood-forming stem cells from a suitable donor are then infused.

The donor immune system may recognise and attack the remaining CMML cells, known as the graft-versus-leukaemia effect.

However, transplantation carries serious risks:

  • Severe infection
  • Graft-versus-host disease
  • Organ toxicity
  • Infertility
  • Relapse
  • Treatment-related death

Because CMML usually affects older adults, many patients are not suitable candidates. Transplant decisions are based on biological fitness rather than age alone and should balance disease risk against transplant risk.

What is the outlook?

The outlook for CMML varies enormously. Published averages combine people with very different disease biology, ages, treatments and other health conditions.

Factors associated with more aggressive disease can include:

  • Higher blast percentage
  • Low haemoglobin
  • Low platelets
  • High white-cell count
  • Circulating immature cells
  • Certain chromosome abnormalities
  • Certain mutations
  • Need for regular transfusions
  • Rapidly worsening blood counts
  • Progressive spleen enlargement

Risk estimates are useful for planning treatment but should not be treated as an expiry date. Statistics describe groups. They are remarkably poor at announcing what will happen to the individual sitting in the clinic.

Living with CMML

Infection precautions

Contact your treatment team promptly if you develop:

  • Fever
  • Chills or shaking
  • Shortness of breath
  • New cough
  • Burning when passing urine
  • New confusion
  • Rapid deterioration

Your team should tell you the temperature threshold that requires urgent assessment. For many immunocompromised patients, a temperature of 38°C or above warrants immediate advice.

Bleeding precautions

Seek medical attention for:

  • Bleeding that does not stop
  • Black bowel motions
  • Blood in the urine
  • Vomiting blood
  • Severe headache after a fall
  • Sudden neurological symptoms
  • Extensive unexplained bruising

Do not start aspirin, anti-inflammatory medicines or supplements that affect bleeding without discussing them with your treating team.

Fatigue

Fatigue may be caused by anaemia, inflammation, treatment, poor sleep, reduced fitness or emotional strain.

Helpful measures may include:

  • Treating reversible causes
  • Gentle regular exercise
  • Planning demanding tasks for periods of higher energy
  • Accepting practical help
  • Maintaining adequate nutrition
  • Discussing persistent sleep or mood problems

Rest is important, but complete inactivity can worsen weakness and fatigue.

Diet

There is no special diet proven to cure or control CMML.

A generally balanced diet is sensible. Patients with very low neutrophil counts or those undergoing transplantation may receive specific food-safety advice.

Herbal products and supplements should be discussed with the haematology team because some can interact with medicines, affect the liver or increase bleeding risk. Natural products remain chemicals, merely with better branding.

Vaccination

Vaccination recommendations depend on treatment and immune function. Inactivated vaccines are generally safer than live vaccines in immunocompromised patients, but timing matters.

Patients should ask their treatment team about:

  • Influenza vaccination
  • COVID-19 vaccination
  • Pneumococcal vaccination
  • Shingles vaccination
  • Vaccinations before or after transplantation

Questions to ask your haematologist

Useful questions include:

  1. Which type and risk category of CMML do I have?
  2. What did my bone marrow biopsy show?
  3. Were any chromosome abnormalities or mutations identified?
  4. Do I need treatment now?
  5. What changes would trigger treatment?
  6. What is the aim of the recommended treatment?
  7. How likely is the treatment to improve my symptoms or blood counts?
  8. What side effects should I expect?
  9. Could I be suitable for a stem-cell transplant?
  10. Is there a clinical trial appropriate for me?
  11. Who should I contact after hours if I develop a fever or bleeding?
  12. How often will my blood tests and appointments be required?

Key points

  • CMML is a rare blood cancer arising in the bone marrow.
  • It causes a persistent increase in abnormal monocytes.
  • It has overlapping features of MDS and MPN.
  • Some patients can be safely monitored without immediate treatment.
  • Treatment may include supportive care, hydroxycarbamide, azacitidine, decitabine, chemotherapy or a clinical trial.
  • Stem-cell transplantation offers the main possibility of cure but is suitable only for selected patients.
  • CMML behaves differently in each person, so treatment must be individualised.
  • New fevers, infection symptoms, significant bleeding or rapid deterioration require urgent medical assessment.