Chronic myelomonocytic leukemia (CMML) is a type of blood cancer. There are a couple of different types of CMML that come with different symptoms and lead to different outcomes. About 1,100 people are diagnosed with CMML each year in the United States, making it a rare type of cancer. Men are twice as likely to get CMML as women are. Additionally, the disease is more common in older adults. About 90 percent of people who are diagnosed with CMML are at least 60 years old.

What Is CMML?

Chronic myelomonocytic leukemia is a type of leukemia that develops from monocytes. Monocytes are white blood cells that play a role in the immune system. Normal monocytes act as a lookout for germs and help coordinate other immune cells to fight infection. People with CMML make high levels of monocytes that are immature. These abnormal monocytes don’t work correctly and crowd out other healthy blood cells.

CMML is not the same disease as chronic myeloid leukemia (CML). CMML and CML develop from different cells, are caused by different gene changes, and are treated with different therapies.

CMML Subtypes

Doctors may group CMML into three different subtypes based on the numbers of blast cells (immature cells) a person has. Note that in some cases, types 0 and 1 are grouped as type 1:

• Type 0 CMML (CMML-0) — Fewer than 2 percent blasts in the blood and 5 percent blasts in the bone marrow
• Type 1 CMML (CMML-1) — 2 percent to 4 percent blasts in the blood or 5 percent to 9 percent blasts in the bone marrow
• Type 2 CMML (CMML-2) — 5 percent to 19 percent blasts in the blood and 10 percent to 19 percent blasts in the bone marrow

Chronic myelomonocytic leukemia can also be categorized in other ways. CMML is highly related to two other rare blood cancers:

• Myelodysplastic syndromes (MDS) — a group of conditions in which the body makes too many abnormal blood cells and too few healthy blood cells
• Myeloproliferative neoplasms (MPNs) — a group of disorders in which the body produces too many blood cells

Experts used to believe that CMML was a type of MDS. More recently, however, researchers have found that CMML cells are also similar to the cells seen in MPNs. Now, experts say that CMML belongs in a separate category that overlaps MDS and MPNs.

About half of people with CMML have a subtype that is similar to MDS (MD-CMML). These people have low or normal levels of white blood cells when they are diagnosed. The other half of people have a CMML subtype that is more similar to an MPN (MP-CMML). This subtype comes with high levels of white blood cells.

Understanding your CMML subtype helps you know more about your prognosis (outlook) and understand which treatments may be most effective.

Causes of Chronic Myelomonocytic Leukemia

Healthy blood cells are produced by stem cells, found inside of certain bones in the bone marrow tissue. When these cells undergo multiple gene changes, they may turn cancerous. Cancer cells grow and divide more quickly than healthy cells.

Certain risk factors may increase a person’s chances of developing cancer-causing gene changes. These include:

• Being over the age of 60
• Being male
• Past exposure to certain chemicals or radiation
• Previous cancer treatments, such as chemotherapy or radiation therapy

Many CMML cells contain gene mutations. These mutations may cause more monocytes to be formed or encourage cells to divide very quickly. Genes that are sometimes mutated in CMML include:

• TET2
• RAS
• ASXL1
• SRSF2

Genes are found on long pieces of DNA called chromosomes. About half of people with CMML also have changes that affect entire chromosomes. Part of a chromosome may be deleted or extra copies of a chromosome may be made. Translocations are also common in people with CMML. During a chromosome translocation, part of one chromosome breaks off and attaches to a different chromosome.

CMML Symptoms

Different subtypes of CMML may cause varying symptoms. People with MD-CMML usually have anemia (low levels of red blood cells), thrombocytopenia (low levels of platelets), and leukopenia (low levels of white blood cells). Not having enough healthy blood cells can lead to several symptoms for people with MD-CMML:

• Feelings of weakness or tiredness
• Petechiae (tiny red spots in the skin)
• Easy bruising
• Bleeding problems
• Frequent infections

People with MP-CMML often have high levels of blood cells, leading to a different set of symptoms:

• Splenomegaly (enlarged spleen)
• Hepatomegaly (enlarged liver)
• Feeling full after not eating very much
• Night sweats
• Bone pain
• Tiredness
• Weight loss

If you notice any of these symptoms, talk to your doctor. It’s more likely that these symptoms are caused by other, more common conditions rather than CMML.

Diagnosis of CMML

Doctors diagnose CMML by studying cells in the blood and bone marrow. Bone marrow samples are obtained through bone marrow aspiration and biopsy. During this procedure, a doctor will remove a small sample of cells and fluid from the bone. Doctors use blood and bone marrow samples to measure levels of monocytes, blasts, and other blood cells. They may also run tests to look for certain gene changes that help rule out other similar types of leukemia.

To be diagnosed with CMML, you need to have:

• High monocyte counts in the blood
• No sign of the Philadelphia chromosome (a gene change found in CML)
• Abnormalities in different types of immature cells
• Fewer than 20 percent blast cells in the blood and bone marrow — if you have more than 20 percent, you will be diagnosed with acute leukemia

Having abnormal blood cell levels on one single test is not enough to be diagnosed with CMML. You need to have unusual test results multiple times. This is because other diseases can cause high or low blood cell levels. For example, low vitamin levels can cause reduced blood cell counts, and infection can cause elevated white blood cell counts. Seeing unusual blood cell levels over a longer period of time helps rule out these other conditions.

Your doctor may also use your blood or bone marrow samples for cytogenetic or molecular tests. These tests can identify changes in chromosomes or genes. Genetic tests help doctors identify the type of leukemia and recommend effective treatments.

Treatments for Chronic Myelomonocytic Leukemia

When recommending a treatment plan, your doctor will consider many different factors. These can include your health, CMML symptoms, and how quickly your CMML is progressing.

Stem Cell Transplant

A stem cell transplant is the only possible cure for CMML — it is the only treatment that may make leukemia go away and not return. People who choose this treatment option will receive a high dose of chemotherapy, which kills off leukemic cells as well as normal blood cells. After chemotherapy, people receive an infusion of blood stem cells from a donor. The stem cells will travel to the bone marrow and make new, healthy blood cells.

Only a portion of people with CMML will undergo a stem cell transplant. This treatment has many serious or even life-threatening risks. Stem cell transplantation is generally only an option for people who:

• Are younger
• Are in good health
• Have more advanced leukemia
• Have a matched donor
• Have leukemia that isn’t responding to other treatments

Chemotherapy

Sometimes, chemotherapy drugs used to treat other types of blood cancers are given to people who have CMML. These can include Hydrea (hydroxyurea) or Cytosar-U (cytarabine). Additionally, three chemotherapy drugs have been approved by the United States Food and Drug Administration (FDA) to treat CMML. They include:

• Vidaza (azacitidine)
• Dacogen (decitabine)
• Inqovi (decitabine and cedazuridine)

Chemotherapy drugs don’t cure CMML. However, they may normalize blood cell counts, which may help reduce symptoms.

Treatments for the Spleen

CMML may make the spleen grow very large. People who are having symptoms from an enlarged spleen may be able to shrink it through radiation therapy. Radiation uses high-energy beams to kill leukemia cells. Alternatively, the spleen may be surgically removed. These treatments are not common for people with CMML.

Supportive Care

The goal of supportive care is not to cure leukemia, but rather to reduce symptoms and improve quality of life. Supportive care is an important part of CMML treatment.

Many people with CMML have low blood counts. One possible treatment for this is a blood transfusion, in which a person with CMML receives blood cells from a donor. Alternatively, people with bleeding problems may be able to get a transfusion of platelets (cell fragments responsible for clotting the blood).

Another supportive care option for people with low blood cell counts is growth factors. These molecules encourage the body to produce new blood cells. Growth factor treatments may include:

• Epo (erythropoietin) — helps the body make red blood cells
• Aranesp (darbepoetin) — another form of erythropoietin that lasts longer
• Neupogen (filgrastim) — encourages the growth of white blood cells and improves the way the body responds to erythropoietin
• Neumega (oprelvekin) — encourages the growth of platelets

CMML often leads to low levels of normal white blood cells. This means that a person with CMML is at risk of getting an infection. Doctors may give antibiotics as a part of supportive care to help treat or prevent infections.

CMML Outlook

Certain prognostic factors can give you an idea of whether you are likely to have a better or worse outcome. Characteristics that influence your prognosis include:

• Your age
• Whether you have other health conditions
• Your blood cell counts
• Which genetic changes your CMML cells have
• Your levels of lactate dehydrogenase (LDH), a molecule that is often increased in your blood when you have cancer

Your CMML subtype also plays a big role in your outlook. People with type 2 CMML generally have worse survival rates:

• About 20 percent of people with type 0 or 1 CMML live for five years or more after being diagnosed
• About 10 percent of people with type 2 CMML live for five years or more after being diagnosed

About 15 percent to 30 percent of people with CMML later develop acute myeloid leukemia (AML). The exact rate can vary based on subtype. About 18 percent of people with type 0 or 1 CMML develop AML within five years. However, about 63 percent of people with type 2 CMML are diagnosed with AML within five years. People with MP-CMML are also more likely to develop AML.

Talk With Others Who Understand

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