Chronic myelomonocytic leukemia (CMML) is a rare type of blood cancer. It starts in the bone marrow, which is the soft inner part of the bones where new blood cells are made. In CMML, the bone marrow makes too many monocytes, a kind of white blood cell that normally helps fight infection. These abnormal cells crowd out healthy blood cells and can also collect in organs such as the spleen and liver.
CMML is called an “overlap” disease. This means it has features of two groups of blood problems: myelodysplastic syndromes (MDS), where blood cells are abnormal and often too low, and myeloproliferative neoplasms (MPN), where the body makes too many blood cells. So CMML can cause both low blood counts and too many white cells at the same time.
Chronic myelomonocytic leukemia (CMML) is a rare cancer of the bone marrow in which too many abnormal white blood cells (especially monocytes) are made, and normal blood cells are crowded out. It has features of both “myelodysplastic syndrome” (MDS – where cells are faulty and low) and “myeloproliferative neoplasm” (MPN – where some cells are too many), so it is called an MDS/MPN overlap disorder. [1]
CMML happens mainly in older adults, usually around 70–75 years of age, and is much less common in young people. Men are affected a bit more often than women. Many patients first discover CMML after routine blood tests show high white blood cells or low hemoglobin or platelets. Over time it can stay stable, slowly get worse, or in some patients change into an aggressive blood cancer called acute myeloid leukemia (AML). [2]
CMML usually develops slowly over months to years. However, it can change into a faster-growing blood cancer called acute myeloid leukemia (AML) in some people. Studies show that about 15–20% of people with CMML may progress to AML over several years.
CMML mainly affects older adults. Most people are over 60–70 years old when they are diagnosed, and it is more common in men than in women. It is rare in young people and children.
Other names
Doctors and scientists use several names for the same disease. Knowing these can help when reading reports or research papers.
Common other names include:
Chronic myelomonocytic leukaemia (UK spelling)
CMML (short form used in most articles)
Myelodysplastic / myeloproliferative neoplasm, chronic myelomonocytic leukaemia (the long “WHO” name that shows it is an overlap disease)
All of these names talk about the same condition: a long-lasting (chronic) blood cancer with too many monocytes and mixed MDS/MPN features.
Types
Doctors divide CMML into types to better understand how serious it is and to plan treatment. The types are based on how many “blast” cells are present and how high the white blood cell count is.
CMML-1
CMML-1 means there are fewer blast cells in the blood and bone marrow. In this type, blasts are under 5% in the blood and under 10% in the bone marrow. This is usually an earlier or less aggressive form, but it still needs close follow-up.
CMML-2
CMML-2 has more blast cells, but still not enough to be called acute leukemia. In this type, blasts are higher (up to 19% in the bone marrow), and the risk of changing into AML is greater. People with CMML-2 usually need closer monitoring and may need stronger treatment.
Myelodysplastic CMML (MD-CMML)
In MD-CMML, the white blood cell count in the blood is lower (under about 13 × 10⁹/L). The main problem is poor production of normal blood cells, so people often have anemia (low red cells), infections (low normal white cells), or easy bruising (low platelets).
Myeloproliferative CMML (MP-CMML)
In MP-CMML, the white blood cell count is higher (13 × 10⁹/L or more). The body is “overproducing” abnormal monocytes and other white cells. This can cause a very enlarged spleen, high counts on blood tests, and more “constitutional” symptoms like night sweats, weight loss, and fevers.
Some people also have CMML with extra eosinophils (a different white cell). This is sometimes called CMML with eosinophilia and may be linked with special gene changes.
Causes and risk factors
Doctors do not know a single exact cause for CMML in most patients. But they do know several risk factors and processes that can make CMML more likely.
Random DNA changes in bone marrow stem cells
CMML begins when a stem cell in the bone marrow develops DNA changes (mutations). These changes are not usually inherited from parents, but happen during life. The mutated cell starts making a clone of abnormal monocytes and other blood cells.Older age
The risk of CMML rises sharply with age. Most people diagnosed are older than 60–65 years. As we age, our stem cells collect more random DNA damage, which may lead to clonal diseases like CMML.Being male
CMML is about twice as common in men as in women. The exact reason is not clear, but large studies have repeatedly seen this difference.Previous chemotherapy (“therapy-related” CMML)
Some people develop CMML years after receiving chemotherapy for another cancer. Certain drugs that damage DNA can later lead to myelodysplastic or myeloproliferative diseases, including CMML.Previous radiotherapy or high-dose radiation exposure
High-dose ionising radiation can injure bone marrow cells. Survivors of nuclear accidents or radiation treatment have a higher risk of myeloid cancers, including CMML.Exposure to environmental carcinogens
Long-term contact with certain chemicals, such as some industrial solvents or other carcinogens, may damage DNA in stem cells and increase the chance of CMML. Evidence is not perfect, but these exposures are considered possible contributors.Cytotoxic agents used for other diseases
Cytotoxic medicines (drugs that kill fast-growing cells) used to treat other blood and solid cancers can sometimes cause later bone marrow damage. A small number of people treated with such drugs later develop CMML or related disorders.Pre-existing myelodysplastic syndrome (MDS)
Some patients have MDS with high monocytes for some time. A part of these cases later crosses the threshold and is reclassified as CMML when the monocyte count and clonal changes meet CMML criteria.Pre-existing myeloproliferative neoplasm (MPN)
Rarely, a person with an MPN such as primary myelofibrosis can develop persistent monocytosis and dysplasia. Over time, their disease may evolve into CMML or a related overlap syndrome.Clonal hematopoiesis of indeterminate potential (CHIP)
In some older adults, a small clone of blood cells with gene mutations (for example in TET2 or ASXL1) exists without clear disease. These clones can expand and progress to CMML in some people, especially if more mutations are gained.TET2 gene mutations
Mutations in the TET2 gene are very common in CMML. This gene helps control DNA methylation, which influences how genes turn on and off. When TET2 is mutated, monocyte production and inflammation can increase.SRSF2 gene mutations
SRSF2 is a splicing factor gene. Changes in this gene disturb normal RNA splicing, which affects how many proteins are made in blood cells. SRSF2 mutations are a characteristic feature in a large share of CMML patients.ASXL1 gene mutations
ASXL1 mutations are linked with more aggressive CMML and poorer outcomes. This gene affects how DNA is packed and how genes are expressed. When it is mutated, stem cells may grow abnormally and resist normal control signals.RAS-pathway mutations (NRAS, KRAS, CBL, etc.)
Mutations that activate the RAS signalling pathway are very common in CMML. They make cells grow and divide more than they should. This helps explain the myeloproliferative, high-white-cell form of the disease.Chronic inflammation and immune activation
People with CMML often have high levels of inflammatory cytokines. Long-lasting inflammation can support the growth of abnormal monocyte clones and damage normal bone marrow function, making CMML more likely to develop or progress.Autoimmune or inflammatory diseases
Around one in five CMML patients has an autoimmune or systemic inflammatory disease, such as vasculitis or arthritis. The exact direction of cause is complex, but immune dysregulation and CMML often coexist and may influence each other.Cardiovascular risk factors and clonal cells
CMML clones release inflammatory substances that are linked to higher cardiovascular events. While heart disease does not cause CMML directly, the same abnormal monocytes that drive CMML also affect blood vessels, linking the two conditions biologically.Family history of myeloid neoplasms (rare)
Most CMML is not inherited. But rare families carry gene changes that increase the risk of several myeloid cancers. In such families, one member might develop CMML while others develop related diseases.Smoking and general carcinogen exposure
Smoking is a known risk factor for various blood cancers. It exposes the bone marrow to many carcinogens that can cause DNA damage. While data for CMML are limited, smoking is considered a general myeloid cancer risk factor.Unknown or idiopathic causes
In many people with CMML, no clear trigger can be found. They have no obvious radiation, chemical, or treatment exposure. In these cases, CMML is called idiopathic, meaning the cause is unknown, and likely due to a combination of age, random mutations, and individual susceptibility.
Symptoms
Symptoms can vary a lot. Some people feel well and are diagnosed only after a routine blood test. Others have many symptoms caused by too many abnormal monocytes, too few healthy cells, or an enlarged spleen and liver.
Tiredness and weakness (fatigue)
Many people with CMML feel very tired, weak, or “out of energy.” This often happens because they have anemia, which means too few red blood cells to carry oxygen around the body.Shortness of breath
Because red blood cells are low, the body may not get enough oxygen during exercise or even at rest. People may feel breathless when walking, climbing stairs, or doing daily activities.Pale skin (pallor)
Low red blood cells can make the skin look pale or washed out. This can be noticed on the face, lips, or inside the eyelids and is a common sign of anemia in CMML.Frequent infections
Abnormal monocytes and other white cells in CMML do not work properly. At the same time, normal infection-fighting cells may be low. This makes infections more common, more severe, or harder to clear.Fever
Some people have fevers that come and go without a clear cause. Fever may result from infections or from the disease itself, because the abnormal cells release inflammatory chemicals.Night sweats
Heavy sweating at night, often soaking clothes or sheets, is a common “B symptom” in many blood cancers. In CMML, night sweats can be linked to high white cell counts and increased inflammatory activity.Unplanned weight loss
People with CMML may lose weight without trying. This can happen because of reduced appetite, increased energy use by the cancer, or chronic inflammation in the body.Easy bruising
Low platelets (thrombocytopenia) make it easier to bruise after minor bumps. People may notice blue or purple marks on the skin, even when they do not remember any injury.Bleeding problems
Nosebleeds, bleeding gums, or heavier bleeding from small cuts can occur when platelets are low or not working well. This can be an early warning sign that the blood’s clotting function is reduced.Fullness or pain under the left ribs (enlarged spleen)
CMML cells often collect in the spleen, making it bigger (splenomegaly). People may feel a heavy or full feeling under the left rib cage, sometimes with pain or discomfort. They may feel full quickly after small meals.Swollen abdomen (enlarged liver and spleen)
Both the spleen and liver can enlarge in CMML. This can make the stomach area look swollen or feel tight, and clothes may feel tighter around the waist.Bone or joint pain
Some people feel aching or pain in bones or joints. This can be due to the bone marrow working abnormally or due to infiltration of abnormal cells.Enlarged lymph nodes
Lymph nodes in the neck, armpits, or groin may become enlarged. This happens when abnormal cells or immune reactions involve the lymphatic system.Skin changes or rashes
Abnormal monocytes can sometimes enter the skin, causing rashes, nodules, or discoloration. Skin changes may also come from low platelets or autoimmune reactions linked with CMML.General feeling of being unwell (malaise)
Many patients describe a vague feeling of being unwell, weak, or “not themselves” for a long time before diagnosis. This non-specific symptom reflects the chronic nature of CMML and the whole-body effects of the disease.
Diagnostic tests
To diagnose CMML, doctors combine the story of symptoms, physical exam findings, blood tests, bone marrow tests, and special lab studies. Several tests are used together to be sure of the diagnosis and to rule out other blood cancers.
Physical exam tests
General physical exam with vital signs
The doctor checks blood pressure, heart rate, breathing rate, and temperature. They look for fever, weight loss, and signs of infection or bleeding. This simple exam gives a first picture of how unwell the person is and guides which urgent tests are needed.Abdominal exam for liver and spleen size
The doctor gently feels (palpates) the abdomen to check if the liver or spleen is enlarged. In CMML, these organs are often bigger than normal because abnormal cells build up inside them. This finding supports a possible blood or bone marrow disease.Lymph node examination
The doctor feels the neck, armpits, and groin for enlarged lymph nodes. Swollen nodes can be a sign that blood cancer cells or reactive immune cells have collected there, which can occur in CMML and other hematologic diseases.Skin and bleeding check
The skin is examined for bruises, tiny red spots (petechiae), rashes, or pale color. These changes can show anemia, low platelets, or infiltration of abnormal cells and help the doctor suspect a blood problem like CMML.
Manual tests
Manual spleen edge palpation
The doctor uses their hands to feel where the spleen edge lies under the left ribs during deep breathing. In CMML the spleen edge may be felt much lower than normal. This simple manual test helps estimate spleen size without machines.Manual liver size assessment
Similarly, the doctor palpates under the right rib cage to feel the liver. A firm, enlarged liver suggests that abnormal cells or extra blood flow are affecting the organ, which is common in CMML and other myeloid neoplasms.Simple strength and walking test
The doctor may ask the person to walk, stand from a chair, or grip the doctor’s fingers. These simple manual tests show how much fatigue, muscle weakness, or breathlessness the person has, helping to judge how much anemia or disease burden is affecting daily life.
Lab and pathological tests
Complete blood count (CBC) with differential
This key blood test measures the number of red cells, white cells, and platelets. In CMML, there is persistent monocytosis (too many monocytes) and often anemia and abnormal platelets. The differential part of the test shows the exact percentage and number of monocytes and other white cells.Peripheral blood smear (blood film)
A drop of blood is spread on a glass slide and looked at under a microscope. In CMML, the smear shows increased monocytes, immature cells (like myelocytes and promonocytes), and dysplastic (abnormal-looking) cells. This microscopic picture strongly supports the diagnosis.Reticulocyte count and red cell indices
These tests show how actively the bone marrow is making new red blood cells and what size they are. They help separate anemia from blood loss, nutrient deficiency, or bone marrow failure as seen in CMML.Bone marrow aspiration
A needle is used to draw liquid bone marrow, usually from the hip bone. The sample is examined to see the number and type of cells, blast percentage, and dysplasia. CMML typically shows increased monocytes and abnormal myeloid cells.Bone marrow biopsy (trephine)
A small core of bone and marrow is removed to look at the structure of the marrow. This test shows how crowded the marrow is and whether abnormal cells are forming clusters. It helps confirm CMML and rule out other conditions.Cytogenetic analysis (karyotyping)
Cytogenetics examines the chromosomes of bone marrow cells under a microscope. It looks for missing pieces, extra pieces, or swapped segments of DNA. These changes help classify CMML, predict outlook, and sometimes guide treatment choices.Fluorescence in situ hybridization (FISH)
FISH uses glowing DNA probes to detect specific chromosome changes that might be too small to see with standard karyotyping. It helps rule out other leukemias (like BCR-ABL1-positive CML) and identify certain rearrangements.Molecular mutation testing (NGS panel)
Next-generation sequencing (NGS) tests look for mutations in many genes at once (such as TET2, SRSF2, ASXL1, and RAS pathway genes). The pattern of mutations confirms that the disease is clonal and helps determine risk and possible targeted treatments.Flow cytometry immunophenotyping
This test uses antibodies and a machine to analyse markers on the surface of blood or marrow cells. It helps confirm that the expanded cells are monocytes and can distinguish CMML from other diseases with similar blood pictures.
Electrodiagnostic tests
Electrocardiogram (ECG)
An ECG records the electrical activity of the heart. While it does not diagnose CMML itself, it is important before and during some treatments that may affect the heart. It helps doctors safely choose medicines for people with CMML who may already be weak or anemic.Nerve conduction studies (if needed)
If a patient with CMML has numbness, tingling, or weakness, nerve conduction studies may be done to check nerve function. These tests are not routine for CMML but can help doctors understand whether symptoms are from the disease, its treatments, or another condition.
Imaging tests
Abdominal ultrasound
Ultrasound uses sound waves to make pictures of organs like the liver and spleen. It is often used to confirm and measure organ enlargement in CMML. Ultrasound is painless and does not use radiation, so it is a common first imaging test.CT or MRI scans
CT and MRI scans give detailed pictures of the inside of the body. They can show the size of the spleen, liver, and lymph nodes, and help rule out other causes of symptoms. They are also sometimes used to plan treatments or monitor changes over time in people with CMML.
Non-pharmacological treatments (therapies and other supports)
1. Careful monitoring and “watchful waiting”
In early or low-risk CMML, sometimes the safest plan is close monitoring instead of immediate strong treatment. The purpose is to avoid side effects until disease truly needs therapy. Doctors regularly check blood counts, spleen size, symptoms like tiredness or infections, and repeat bone marrow tests if needed. The mechanism is simple: by watching trends over time, doctors can act quickly if CMML starts to progress, while protecting quality of life when it is stable. [4]
2. Infection-prevention hygiene
Because CMML and its treatments can weaken immunity, strong infection prevention is a daily “treatment.” The purpose is to lower the chance of serious bacterial, viral, or fungal infections. Patients are taught to wash hands often, avoid close contact with people who are sick, practice safe food handling, and keep cuts clean. The mechanism is practical: fewer germs reaching the body means fewer infections when white blood cells are weak or not working properly.
3. Vaccinations (non-live, as advised)
Non-live vaccines such as flu, COVID-19, and pneumococcal vaccines can reduce the risk of severe infections. The purpose is to “train” the immune system against common pathogens before treatment makes it weaker. The mechanism is immune priming: vaccine antigens stimulate antibody and memory cell formation, so the body responds faster when real infection appears. Doctors choose vaccines and timing carefully around chemotherapy or transplant. [5]
4. Exercise and physical activity program
Gentle, regular activity such as walking, stretching, or light resistance training helps keep muscles strong, supports heart health, and reduces fatigue. The purpose is to fight weakness, depression, and loss of independence. The mechanism is multi-factorial: exercise improves blood flow, raises mood chemicals in the brain, and reduces inflammation, which together can improve energy and daily function in CMML.
5. Individualized nutrition support
Seeing a dietitian helps patients plan food that maintains weight, muscle, and immune health even when appetite is poor. The purpose is to prevent malnutrition, vitamin deficiency, and muscle loss. The mechanism is targeted intake of enough calories, protein, vitamins, and minerals to support bone marrow, repair tissues, and help the body cope with infections and treatments.
6. Smoking cessation
Stopping smoking is strongly recommended because tobacco smoke damages blood vessels, weakens lungs, and increases infection and cancer risks. The purpose is to reduce complications such as pneumonia, heart disease, and secondary cancers. The mechanism is straightforward: removing constant toxic exposure lets the lungs and vessels function better, improves oxygen delivery, and may reduce additional DNA damage in blood-forming cells.
7. Alcohol moderation or avoidance
Limiting or avoiding alcohol protects the liver and bone marrow, both of which can already be stressed by CMML and its treatments. The purpose is to lower the risk of liver damage, bleeding, and drug interactions. The mechanism is lowering toxic stress on liver cells, which improves metabolism of chemotherapy drugs and reduces risk of worsened anemia or low platelets related to alcohol use.
8. Fatigue management and energy conservation
Chronic tiredness is common in CMML. Occupational therapists teach “energy budgeting,” such as planning rest breaks, prioritizing tasks, and using tools or help for heavy activities. The purpose is to maintain independence and quality of life. The mechanism is practical: by spreading energy across the day and avoiding sudden overexertion when hemoglobin is low, patients feel less overwhelmed and function better.
9. Psychological counseling and support groups
Living with CMML can cause anxiety, sadness, or fear about the future. Counseling and peer support groups give a safe space to talk, learn coping skills, and feel less alone. The purpose is to protect mental health and improve resilience. The mechanism is emotional processing and social connection, which can reduce stress hormones and improve sleep, treatment adherence, and overall wellbeing.
10. Sleep hygiene and routine
Good sleep habits – regular bedtime, quiet dark room, limited caffeine, and managing night-time worries – are simple but powerful. The purpose is to improve daytime energy, mood, and immune function. The mechanism is that deep sleep helps the body repair tissues, regulate hormones, and support immune cell activity, which is especially important in blood cancers.
11. Fall-prevention and home safety
When anemia, weakness, or low platelets increase the risk of fainting and bleeding, making the home safer becomes a “treatment.” The purpose is to prevent injuries that could be serious. The mechanism is reducing hazards: removing loose rugs, adding grab bars, good lighting, and supportive footwear lowers the chance of falls and dangerous head or internal bleeding.
12. Oral and dental care
Low platelets and chemotherapy can cause gum bleeding and mouth sores. Gentle brushing, soft toothbrushes, alcohol-free mouthwash, and regular dental checks help a lot. The purpose is to prevent infections and painful sores. The mechanism is keeping the mouth’s bacterial balance healthy and avoiding trauma to fragile tissues, which lowers infection entry points when immunity is weak.
13. Skin protection and wound care
Thin, fragile skin and low white cells mean small cuts can become big problems. Using moisturizers, sun protection, and protective clothing, and treating minor wounds early is important. The purpose is to prevent skin infections and ulcers. The mechanism is keeping the skin barrier strong and quickly removing germs from cuts, which reduces the risk of cellulitis and sepsis.
14. Managing cardiovascular risk factors
High blood pressure, diabetes, and high cholesterol can worsen outcomes in older adults with CMML. Lifestyle steps plus medicines for these conditions are supportive treatments. The purpose is to reduce heart attacks, strokes, and organ damage. The mechanism is better blood vessel health and improved circulation, which help patients tolerate CMML treatments and recover from infections more safely.
15. Limiting exposure to harmful chemicals
Where possible, avoiding benzene, solvents, pesticides, and unnecessary radiation is sensible. The purpose is to reduce further damage to bone marrow DNA. The mechanism is simple: fewer toxic exposures mean less additional genetic injury to blood-forming cells, which may help limit disease progression or secondary cancers, although this cannot “cure” CMML.
16. Early palliative care involvement
Palliative care is not only for end of life; it is a team that focuses on comfort, symptom control, and what matters to the patient. The purpose is to control pain, breathlessness, itching, or anxiety at any stage. The mechanism is a whole-person approach, combining medicines, counseling, and practical support to improve life quality alongside cancer-directed treatment.
17. Occupational and work adjustments
Many people want to keep working or studying, but full-time schedules can be too heavy. Flexible hours, work-from-home options, or lighter duties can help. The purpose is to protect energy and reduce stress while maintaining identity and income. The mechanism is matching work demand to current physical ability, which lowers burnout, infections from overexposure, and emotional distress.
18. Financial and social support services
Cancer care can be expensive and time-consuming. Social workers help patients access insurance benefits, travel help, or disability support. The purpose is to reduce money stress, which may worsen mental health and treatment adherence. The mechanism is practical relief: when basic needs are safer, patients can focus more on health and following treatment plans.
19. Spiritual or meaning-focused support (if desired)
Some patients find strength in faith, philosophy, or personal values. Talking with a chaplain or trusted leader can support them. The purpose is to help people cope with uncertainty and fear, and find meaning. The mechanism is emotional comfort and hope, which can improve mood and motivation to continue helpful treatments.
20. Carefully chosen integrative therapies
Gentle yoga, breathing exercises, massage, or acupuncture (with platelets high enough and doctor approval) may ease pain, anxiety, and nausea. The purpose is to add comfort without replacing standard medical care. The mechanism is relaxation, improved blood flow, and activation of natural pain-control pathways. These must always be discussed with the care team to avoid interactions or bleeding risks.
Drug treatments for CMML
Note: Exact drugs, doses and timing are highly individual. Below are common options used by specialists; they must never be started without a hematologist.
1. Azacitidine (injectable)
Azacitidine is a hypomethylating agent that changes abnormal DNA methylation patterns in bone marrow cells to help them mature more normally. It is approved for myelodysplastic syndromes, which include CMML in the classic FAB classification. [6] It is usually given as daily injections for several days every 28-day cycle, with dose calculated from body surface area. The purpose is to improve blood counts, reduce transfusion needs, and delay progression to AML. The mechanism involves reactivating silenced genes and promoting more normal cell death in cancerous precursors. Main side effects are low blood counts, nausea, vomiting, injection site reactions, and fatigue.
2. Decitabine (IV infusion)
Decitabine is another hypomethylating agent that is FDA-approved for MDS, including chronic myelomonocytic leukemia as part of the defined subtypes. [7] It is usually given by vein over several days in repeating cycles. The purpose is similar to azacitidine: improve bone marrow function, reduce transfusion requirements, and slow disease. The mechanism is incorporation into DNA and inhibition of DNA methyltransferase, which changes gene expression and can restore more normal cell growth and death. Side effects include severe neutropenia, thrombocytopenia, infections, fevers, and fatigue, so patients need close monitoring.
3. Oral decitabine/cedazuridine (INQOVI)
Decitabine/cedazuridine is an oral tablet that combines decitabine with a second drug that stops it being broken down in the gut, allowing similar drug levels to IV decitabine. It is FDA-approved for adults with MDS including chronic myelomonocytic leukemia. [8] The purpose is to provide hypomethylating therapy in a more convenient oral form for suitable patients. The mechanism is the same DNA hypomethylation effect as IV decitabine, while cedazuridine blocks gut enzymes so more medicine reaches the blood. Side effects are similar: low blood counts, infections, fatigue, and GI upset, so it also needs strict blood monitoring.
4. Hydroxyurea
Hydroxyurea is an oral chemotherapy used mainly for “proliferative” CMML with very high white counts and big spleen. It is considered the drug of choice to control cell overgrowth and reduce organ enlargement in many guidelines. [9] The purpose is palliative control of symptoms like fullness, pain, and high-viscosity blood problems, not cure. The mechanism is inhibition of DNA synthesis in rapidly dividing cells, which lowers white blood cell and monocyte counts. Side effects can include bone marrow suppression, mouth sores, GI upset, and long-term skin changes, so doses are slowly adjusted by the hematologist.
5. Low-dose cytarabine
Low-dose cytarabine (Ara-C) is a traditional chemotherapy sometimes used in older or frail CMML patients when hypomethylating agents are not suitable. The purpose is to reduce blast counts and control symptoms from bone marrow failure. The mechanism involves blocking DNA synthesis in dividing leukemia cells, causing them to die. It is usually given as small injections under the skin for several days in cycles. Common side effects include marrow suppression, infections, nausea, and hair thinning, so it is used carefully.
6. AML-type induction chemotherapy
For CMML that has transformed into acute myeloid leukemia or has very high blast counts, standard AML induction regimens (such as a combination of cytarabine and an anthracycline) may be used. The purpose is to quickly reduce leukemia burden and achieve remission before possible stem cell transplant. The mechanism is strong killing of rapidly dividing cells through DNA damage and inhibition of repair. However, side effects are intensive: severe infections, bleeding, hair loss, organ strain, and long hospital stays, so this is usually reserved for fit patients.
7. Erythropoiesis-stimulating agents (ESAs)
Drugs like epoetin alfa or darbepoetin can be used off-label in selected CMML patients with symptomatic anemia and low endogenous erythropoietin levels. The purpose is to boost red blood cell production and reduce transfusion needs. The mechanism is stimulation of red cell precursors in the bone marrow through erythropoietin receptors. Side effects can include high blood pressure, clot risk, and headaches, so doctors only use ESAs when benefits seem to outweigh risks.
8. Granulocyte colony-stimulating factor (G-CSF)
G-CSF (such as filgrastim) is sometimes given briefly to raise neutrophil counts during severe infections or in specific situations, but it must be used carefully in CMML because it can also stimulate malignant myeloid cells. The purpose is urgent support of host defense when infections are life-threatening. The mechanism is direct stimulation of neutrophil production and release from bone marrow. Side effects can include bone pain, very high white counts, and in theory possible disease flare, so hematologists use it cautiously.
9. Iron chelation therapy
Patients who receive many blood transfusions for anemia may develop iron overload, which can damage the heart and liver. Drugs like deferasirox can remove extra iron from the body. The purpose is to protect organs and improve long-term outcomes in heavily transfused patients. The mechanism is binding free iron so it can be excreted in stool or urine. Side effects include kidney and liver test changes, GI upset, and rash, so regular blood tests are needed.
10. Antimicrobial prophylaxis (antibiotics, antivirals, antifungals)
In high-risk patients with very low neutrophils or after intensive treatment, doctors may prescribe preventive antibiotics, antivirals, or antifungals. The purpose is to lower the chance of serious infections when immune defenses are extremely weak. The mechanism is direct killing or blocking of bacteria, viruses, or fungi before they cause illness. Side effects vary but can include diarrhea, liver test changes, and drug interactions, so choices are individualized.
11. Tumor lysis prevention (allopurinol or rasburicase)
When strong chemotherapy rapidly kills leukemia cells, breakdown products can harm the kidneys. Drugs like allopurinol or rasburicase are used to lower uric acid levels. The purpose is to prevent or treat tumor lysis syndrome. The mechanism is either blocking uric acid production or breaking down existing uric acid in the blood. Side effects can involve allergic reactions or changes in liver and kidney tests, so patients are watched closely during the first cycles of intensive therapy.
12. Platelet transfusions
Although not a “drug” in the usual sense, platelet transfusions are a key treatment when platelet counts are very low or bleeding occurs. The purpose is to stop or prevent dangerous bleeding, especially in the brain or gut. The mechanism is direct replacement of missing platelets so clots can form properly. Risks include transfusion reactions, infections (rare with screening), and development of antibodies, so transfusions are given when clearly needed.
13. Red blood cell transfusions
Red blood cell transfusions are common in CMML with severe anemia. The purpose is to quickly raise hemoglobin to improve breathlessness, chest pain, and extreme fatigue. The mechanism is simple: transfused red cells immediately carry more oxygen to tissues. Side effects can include fluid overload, iron overload, and immune reactions, which is why doctors balance benefits with long-term risks.
14. Proton pump inhibitors and gastric protectants
Patients on steroids, NSAIDs, or some chemotherapies may receive medicines such as proton pump inhibitors to protect the stomach lining. The purpose is to reduce stomach ulcers and bleeding in already vulnerable patients. The mechanism is lowering acid production so the stomach and duodenal lining can better resist injury. Long-term side effects can include nutrient malabsorption or infection risk, so duration is kept as short as is safe.
15. Anti-nausea (antiemetic) medicines
Drugs such as ondansetron, metoclopramide, or other antiemetics are often given to control nausea and vomiting from chemotherapy or iron chelators. The purpose is to help patients tolerate treatment and maintain nutrition. The mechanism is blocking specific receptors in the brain and gut that trigger nausea signals. Side effects can include constipation, headache, or drowsiness depending on the drug.
16. Pain-relief medicines
From bone pain to spleen discomfort, pain can be part of CMML. Analgesics from paracetamol to, when needed, opioids may be used. The purpose is to keep pain controlled so patients can sleep, move, and eat. The mechanism is blocking pain pathways in the nervous system or reducing inflammation. Doctors choose the lowest effective dose and carefully watch for side effects like constipation, liver strain, or dependence.
17. Antipruritic (itch-relief) medicines
Some patients have itching due to high white cells, dry skin, or treatment side effects. Antihistamines, topical creams, or certain antidepressants may help. The purpose is to break the itch–scratch cycle, which can cause infections and poor sleep. The mechanism is blocking histamine, calming nerve signals, or moisturizing and soothing the skin barrier.
18. Mood and sleep medicines (if needed)
When anxiety, depression, or insomnia become severe, carefully chosen antidepressants or sleep aids may be prescribed. The purpose is to support mental health and allow restorative sleep. The mechanism is adjusting brain chemicals such as serotonin or GABA to stabilize mood and reduce arousal. Doctors must check for drug interactions with cancer medicines and use the lowest effective doses.
19. Targeted or trial drugs
In some centers, CMML patients with specific gene mutations may join clinical trials of targeted therapies or novel agents. The purpose is to block abnormal pathways driving the leukemia. The mechanism varies (for example, inhibiting abnormal tyrosine kinases or signaling proteins), and side effects depend on the specific drug. Because evidence is still developing, these are usually used in studies or after standard options. [10]
20. Supportive endocrine and metabolic drugs
Steroids, insulin adjustments, or other hormonal medicines may be needed to manage complications from chemotherapy or from other pre-existing illnesses. The purpose is to keep the body’s internal balance safe during treatment. The mechanism is replacing or adjusting key hormones and metabolic pathways so that other therapies can be given more safely and comfortably.
Dietary molecular supplements (with caution)
Always check every supplement with your hematologist. Some “natural” products can interact with chemotherapy or affect bleeding.
1. Vitamin D
Vitamin D helps bone health, immune function, and muscle strength, and low levels are common in older adults and people who stay indoors. The purpose of supplementing a deficiency is to support bone marrow environment, muscle strength, and infection defense. The mechanism is acting through vitamin D receptors on immune and bone cells to regulate calcium, inflammation, and immune responses. Doctors usually aim for a safe blood level rather than a fixed dose, because too much vitamin D can cause high calcium and kidney problems.
2. Vitamin B12
Some patients with CMML or overlapping MDS can have low B12, which worsens anemia and nerve problems. The purpose of B12 supplementation (by tablet or injection when low) is to support healthy red blood cell production and nerve function. The mechanism is providing a key cofactor for DNA synthesis in bone marrow cells and for myelin in nerves. Normal doses are safe, but very high, unnecessary doses bring no added benefit and may waste money.
3. Folate (vitamin B9)
Folate deficiency can also worsen anemia and cause big red cells. When tests show low folate, replacement supports more normal blood formation. The purpose is to help DNA building blocks in dividing cells. The mechanism is providing a key vitamin for nucleotide synthesis, which is essential for red and white blood cell production. Folate should be guided by blood tests, because excess folic acid can sometimes hide B12 deficiency, which still harms nerves.
4. Omega-3 fatty acids (fish oil)
Omega-3 fats from fish oil or algae have anti-inflammatory effects and may support heart and vessel health. The purpose is to help cardiovascular health and possibly relieve some joint pains or inflammation in long-term illness. The mechanism is altering cell membrane lipids and reducing production of inflammatory eicosanoids. High doses can slightly thin the blood, so in CMML patients with low platelets or on anticoagulants, any fish oil dose must be checked with the doctor.
5. Probiotics (with care)
Probiotics are “good bacteria” supplements that may help restore gut flora after antibiotics. The purpose is to reduce diarrhea and support gut barrier function. The mechanism is colonization of the gut with beneficial strains that compete with harmful microbes and modulate immune responses. However, in patients with very low neutrophils or central lines, certain probiotic strains have rarely caused bloodstream infections, so hematologists often avoid them in the most immunocompromised patients.
6. Vitamin C
Vitamin C acts as an antioxidant and is important for collagen, wound healing, and immune function. The purpose of correcting deficiency is to support skin, gums, and infection defense. The mechanism is scavenging free radicals and supporting white cell function and iron absorption. Normal dietary doses are safe; very high oral or IV “mega-doses” are not recommended outside clinical trials because they may interfere with some treatments or cause kidney stones.
7. Zinc
Zinc is essential for immune cell function and wound healing. When zinc is low (for example after long poor appetite or diarrhea), small supplements may be used. The purpose is to correct deficiency so immune responses can work properly. The mechanism is supporting many enzymes in DNA repair, antioxidant defense, and cell division. Excess zinc can cause nausea, block copper absorption, and disturb cholesterol, so doses must stay within medical advice.
8. Selenium
Selenium is another trace mineral involved in antioxidant enzymes such as glutathione peroxidase. The purpose of supplementing confirmed deficiency is to support antioxidant defenses and thyroid function. The mechanism is helping enzymes detoxify harmful oxygen radicals produced during inflammation or chemotherapy. High selenium is toxic and can cause hair loss, nail changes, and nerve problems, so only modest, doctor-approved doses are appropriate.
9. Curcumin (turmeric extract)
Curcumin is the active compound in turmeric and has anti-inflammatory and antioxidant properties in lab studies. The purpose, when approved by the care team, may be symptom relief of joint pains or inflammation. The mechanism is blocking certain inflammatory pathways (such as NF-κB) and scavenging free radicals in experimental models. It can affect blood clotting and drug-metabolizing enzymes, so it must never be started without checking interactions with CMML treatments.
10. Protein supplements (whey, plant protein)
When appetite is low, protein shakes can help patients achieve enough protein to preserve muscle mass. The purpose is to prevent muscle wasting and support immune and wound healing processes. The mechanism is providing easily digested amino acids for building and repairing tissues. However, kidney function must be considered, and sugar content in some shakes may not be suitable for people with diabetes, so a dietitian’s advice is important.
Immunity-supporting / regenerative drugs and stem-cell related therapies
1. G-CSF (granulocyte colony-stimulating factor)
G-CSF can be used for short periods to raise neutrophil counts during severe, life-threatening infections. The purpose is emergency support of the immune system when neutrophils are dangerously low. The mechanism is stimulating the bone marrow to release and produce more neutrophils. In CMML it must be used very carefully, because it might also stimulate leukemia cells, so decisions are case-by-case by experienced hematologists.
2. GM-CSF (granulocyte-macrophage colony-stimulating factor)
GM-CSF stimulates several types of white blood cells. The purpose is similar to G-CSF in certain settings, such as after stem cell transplantation or intensive chemotherapy. The mechanism is binding to receptors on progenitor cells and promoting their growth and maturation into neutrophils, monocytes, and other cells. Side effects can include fever, bone pain, and fluid retention, and its use in CMML is very specialized.
3. Intravenous immunoglobulin (IVIG)
IVIG is a purified antibody preparation from many donors. It may be used in patients with very low antibody levels or recurrent serious infections. The purpose is to temporarily give ready-made antibodies to help fight infections. The mechanism is passive immunity: infused antibodies can neutralize pathogens and modulate immune reactions. It is given by infusion and can cause headaches, allergic reactions, or kidney strain, so monitoring is essential.
4. Thrombopoietin receptor agonists (carefully selected cases)
Drugs like eltrombopag or romiplostim stimulate platelet production and are used in some platelet disorders. In selected MDS cases, they may help reduce bleeding and transfusion needs, but their use in CMML is cautious and often limited to trials or special situations. The purpose is to increase platelet counts safely. The mechanism is activating thrombopoietin receptors on megakaryocyte precursors, promoting platelet formation. Because of concerns about promoting blasts in some settings, they are not routine CMML therapy and require expert judgment.
5. Stem-cell mobilizing agents (e.g., G-CSF ± plerixafor before collection)
Before an allogeneic stem cell transplant, donors or sometimes patients need their stem cells collected. G-CSF with or without plerixafor is used to move stem cells from the marrow to the blood for collection. The purpose is to obtain enough healthy stem cells for transplantation. The mechanism is blocking certain signals that keep stem cells in the marrow, allowing them to circulate. Side effects include bone pain and rare spleen problems, so donors and patients are closely watched.
6. Allogeneic hematopoietic stem cell transplantation (HSCT)
HSCT is the only proven curative therapy for CMML, where diseased marrow is replaced with donor stem cells after strong conditioning treatment. [11] The purpose is to give the patient a new, healthy blood-forming system and a donor immune system that can attack remaining leukemia cells (“graft-versus-leukemia” effect). The mechanism combines high-dose chemotherapy (and sometimes radiation) to destroy diseased cells, followed by infusion of donor stem cells that engraft in the marrow. It carries high risks, including infections, graft-versus-host disease, and transplant-related death, but in carefully selected patients it can give long-term survival.
Surgical or procedural treatments
1. Allogeneic stem cell transplantation procedure
Although driven by medicines, HSCT itself is a complex medical procedure similar to major treatment rather than a simple infusion. The process requires insertion of a central venous catheter, intensive supportive care, and sometimes admission to a special transplant unit. The purpose is curative intent for suitable patients. The “surgical” aspects include line placement and sometimes biopsy or other interventions before and after transplant, making it one of the most intensive treatments offered for CMML.
2. Splenectomy (removal of the spleen)
In rare cases with massive spleen enlargement causing severe pain, early satiety, or low blood counts from spleen “trapping,” and when drugs like hydroxyurea fail, surgeons may remove the spleen. The purpose is to relieve symptoms, improve count control, and reduce transfusion needs. The mechanism is removing the main site where abnormal cells and platelets are being destroyed or pooled. Risks are significant, including bleeding, infection, and lifelong higher risk of certain bacterial infections, so patients need vaccines and careful follow-up.
3. Central venous catheter insertion
Many CMML patients need frequent blood tests, transfusions, or intravenous chemo. A central venous catheter or port is placed through a minor surgical procedure. The purpose is to provide safe, long-term venous access without repeated needle sticks. The mechanism is routing a soft tube into a large vein, usually near the heart, under sterile conditions. Risks include infection and blood clots, so careful care of the line is essential.
4. Diagnostic and therapeutic biopsies
Bone marrow biopsies are not surgeries in the classic sense, but they are invasive procedures that guide treatment decisions. Sometimes lymph node or organ biopsies are also taken to rule out other diseases or complications. The purpose is to accurately stage disease, assess response, or evaluate new problems. The mechanism is removing a tiny tissue sample under local anesthesia for microscopic and genetic analysis.
5. Emergency surgeries for complications
Very rarely, CMML or its treatments lead to complications such as severe bowel infections, bleeding, or abscesses that require surgical management. The purpose is to treat life-threatening problems that cannot be controlled with medicines alone. The mechanism is direct repair or removal of damaged tissue, combined with antibiotics, transfusions, and intensive care. Surgeons and hematologists work closely to balance bleeding risk and infection risk in these emergency situations.
Key prevention and risk-reduction strategies
While CMML itself often cannot be fully prevented, certain steps may lower risks of complications or treatment-related problems:
Avoiding smoking to reduce additional cancer, lung, and blood vessel damage.
Limiting alcohol to protect liver and marrow and avoid worsening bleeding.
Using workplace protection (masks, ventilation) if exposed to chemicals like solvents or pesticides.
Vaccination against flu, COVID-19, and pneumonia as recommended to prevent severe infections.
Prompt infection treatment – seeking medical care early for fever, cough, or wounds.
Regular cancer follow-up so any changes in blood counts or symptoms are caught early.
Managing chronic illnesses like diabetes, hypertension, and heart disease to reduce overall risk.
Healthy weight and activity to support heart, lungs, and muscle strength during treatments.
Careful medicine review so other drugs do not harm marrow or interact with CMML therapies.
Sun and skin protection to reduce skin cancer and infection risk, especially when immune-suppressed.
When to see a doctor urgently
People with CMML should contact their doctor or emergency services quickly if they notice red-flag symptoms such as high fever, chills, severe sore throat, shortness of breath, chest pain, confusion, sudden severe headache, heavy bleeding, black or bloody stools, or rapidly worsening fatigue and dizziness. These signs can indicate serious infections, bleeding, or heart and lung complications that need fast treatment. Any new large bruises, rash with fever, or sudden big increase in spleen pain or abdomen size should also be checked immediately. Regular planned visits are important, but new or rapidly worsening symptoms should never wait.
What to eat and what to avoid
Eat plenty of fruits and vegetables that are well washed and, if neutrophils are very low, often cooked rather than raw, to give vitamins and antioxidants while reducing germ exposure.
Choose whole grains like brown rice, oats, and whole-wheat bread to provide steady energy and fiber for digestive health.
Include lean proteins such as cooked fish, eggs, poultry, beans, and tofu to support muscle repair and immune cell production.
Use healthy fats from olive oil, nuts, seeds, and avocado in moderate amounts to support heart health and calorie intake.
Drink enough safe fluids like water and herbal teas to prevent dehydration, especially if having fevers or diarrhea.
Avoid undercooked or raw animal foods such as sushi, runny eggs, and rare meat when neutrophil counts are low, to lower infection risk.
Avoid unpasteurized dairy and juices that may contain harmful bacteria in immunocompromised people.
Limit processed and very salty foods like chips, instant noodles, and cured meats, which can worsen blood pressure and overall health.
Limit sugary drinks and sweets to reduce weight gain, high blood sugar, and tooth problems, especially when steroids are used.
Do not start herbal or “immune booster” products (such as strong green tea extracts, high-dose curcumin, or unknown mixtures) without your hematologist’s approval, because some can interfere with chemotherapy, increase bleeding, or stress the liver.
Frequently asked questions (FAQs)
1. Is CMML a type of leukemia or myelodysplastic syndrome?
CMML is both and is officially classified as an overlap disease between myelodysplastic syndromes (faulty cell production) and myeloproliferative neoplasms (over-production of some cells). This means it can show low counts and high counts at the same time, which is why treatment plans are so individualized. [12]
2. Can CMML be cured?
For most patients, CMML is a chronic disease managed over years with medicines and supportive care. The only proven curative option for some people is allogeneic stem cell transplantation, which is intensive and not suitable for everyone. Many patients, especially older ones, are treated with the goal of control and good quality of life rather than cure. [13]
3. Who usually gets CMML?
CMML mainly affects older adults, often in their seventies, and is rare in children or young adults. There is a slight male predominance. Previous chemotherapy or radiation for other cancers can sometimes lead to “therapy-related” CMML, but many people have no clear cause. [14]
4. What symptoms should I watch for?
Common symptoms include tiredness from anemia, easy bruising or bleeding from low platelets, frequent infections from abnormal white cells, night sweats, weight loss, fever, and a feeling of fullness or pain under the left ribs from an enlarged spleen. Any sudden worsening of these symptoms should be shared with the care team.
5. Why does my doctor talk about “blast percentage”?
Blasts are immature blood cells in the bone marrow. In CMML, a higher blast percentage means the disease is more aggressive and closer to transforming into acute leukemia. Treatments such as hypomethylating agents are often started when blasts rise, and transplant may be discussed for eligible patients, because outcomes are worse when blast counts are high.
6. What is the role of genetic testing in CMML?
Modern CMML care includes testing for gene mutations and chromosomal changes in the bone marrow. These results help doctors estimate prognosis (risk scores) and sometimes choose treatments or trials. Certain mutations are linked to higher risk of transformation or poorer outcomes, so genetics is now a standard part of CMML assessment in many centers.
7. How long will I need treatment like azacitidine or decitabine?
Hypomethylating agents usually need several cycles before benefits show, and responders often continue them as long as they work and side effects are manageable. Stopping too early may lead to relapse, so doctors review response regularly with blood tests and sometimes repeat marrow exams, and decide together with the patient how long to continue. [15]
8. What are the main risks of stem cell transplant?
Allogeneic transplant can bring long-term remission but also serious risks such as severe infections, organ damage from conditioning chemotherapy, and graft-versus-host disease where donor cells attack the patient’s tissues. Death related to the procedure is an important risk. This is why transplant decisions are made very carefully, balancing disease risk against transplant risk. [16]
9. Can CMML come back after transplant?
Yes, relapse can occur even after a successful transplant, although many patients achieve durable remissions. Doctors are studying factors that predict relapse and strategies to lower this risk, such as careful timing of transplant, choice of conditioning regimen, maintenance therapies, and donor lymphocyte infusions in selected cases.
10. Is it safe to travel if I have CMML?
Many patients can travel when their disease is stable, but timing and destination must be discussed with the care team. You may need updated vaccines, a letter summarizing your condition, enough medicines, and information about hospitals at your destination. Travel may be delayed during very low blood counts or right after chemotherapy or transplant because infection risk is high.
11. Can I work or go to school with CMML?
Many people continue working or studying with adjustments to schedule and workload. The key is honest communication with your doctor, employer, or school, and listening to your body. Some days may require rest, and infection-heavy environments may not be safe during strong treatment, so plans often change over time.
12. Will CMML affect my family members’ risk?
Most CMML cases are not strongly inherited and do not mean your family will definitely get it. However, very rare familial syndromes and shared environmental exposures exist. If there is a strong family history of blood cancers, genetic counseling may be offered. In general, relatives are advised to follow routine health checks and healthy lifestyle steps.
13. Are there new treatments being studied?
Yes. Clinical trials are exploring targeted agents, combination regimens with hypomethylating drugs, and better transplant strategies. These research efforts aim to improve response rates, lower side effects, and extend survival. Patients may ask their hematologist about suitable trials based on their disease risk and location. [17]
14. What can I do personally to help my treatment work better?
Keeping appointments, taking medicines exactly as prescribed, reporting side effects early, eating and drinking well, staying as active as you safely can, and seeking emotional support all help. Avoiding smoking and heavy alcohol, and checking new medicines or supplements with your hematologist, also improves safety and effectiveness of care.
15. Where can I find reliable information and support?
Reliable information usually comes from national cancer societies, leukemia foundations, academic hospital websites, and peer-reviewed medical journals. Patient support groups, both local and online, can offer shared experiences and tips for daily life. Your hematology team can guide you towards trusted resources in your language and region. [18]
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 25, 2025.
