Chronic myelomonocytic leukemia (CMML) starts in blood-forming cells in the bone marrow and invades the blood.

Cells in nearly any part of the body can become cancer and can spread to other areas of the body. To learn more about how cancers start and spread, see What Is Cancer?

Normal bone marrow

Bone marrow is found inside certain bones such as the skull, ribs, pelvis, and spine. It's made up of blood-forming cells, fat cells, and supporting tissues that help the blood-forming cells grow. A small fraction of the blood-forming cells are a special type of cell known as stem cells. Stem cells are needed to make new cells. When a stem cell divides, it makes 2 cells: one cell that stays a stem cell and another cell that can keep changing and dividing to make blood cells.

There are 3 types of blood cells: red blood cells, white blood cells, and platelets.

Red blood cells pick up oxygen in the lungs and carry it to the rest of the body. These cells also bring carbon dioxide back to the lungs. Having too few red blood cells is called anemia. People with anemia can look pale and feel tired and weak. Severe anemia can cause shortness of breath.

White blood cells (also called leukocytes) are important in fighting infection.

• Lymphocytes are immune cells in the bone marrow, the blood, and in lymph nodes. Some kinds of lymphocytes make the antibodies that help your body fight germs. Other kinds directly kill invading germs by making toxic substances that damage the cells.
• Granulocytes are white blood cells that destroy bacteria. They contain granules that are made up of enzymes and other substances which can destroy germs that cause infections. In the bone marrow, granulocytes develop from young cells called myeloblasts. The most common type of granulocyte is the neutrophil; which is crucial in fighting bacteria. Other types of granulocytes are basophils, and eosinophils. When the number of neutrophils in the blood is low, it is called neutropenia. This can lead to severe infections.
• Monocytes are related to the granulocyte family. They also help protect you against bacteria. The early cells in the bone marrow that turn into monocytes are called monoblasts. When monocytes leave your bloodstream and go into tissue, they become macrophages. Macrophages can destroy germs by surrounding and digesting them. They're also important in helping lymphocytes recognize germs and start making antibodies to fight them.

Platelets are thought of as a type of blood cell, but they're really small pieces of a cell. They start as a large cell in the bone marrow called the megakaryocyte. Pieces of this cell break off and enter your bloodstream as platelets, which you need for your blood to clot. Platelets plug up damaged areas of blood vessels caused by cuts or bruises. If you have a shortage of platelets (a condition called thrombocytopenia) you can bleed and bruise a lot.

Features of chronic myelomonocytic leukemia

• People with CMML may have shortages of some blood cells, but a main problem is too many monocytes. (at least 1,000 per mm³). Often, the monocyte count is much higher, causing their total white blood cell count to become very high as well.
• Usually there are some abnormal cells, called blasts, in the bone marrow. The amount of blasts in CMML is below 20%.
• Many people with CMML have enlarged spleens (an organ that lies just below the left rib cage).
• About 15% to 30% of people with CMML go on to develop acute myeloid leukemia.
• The DNA inside the abnormal cells does not have certain changes in the genes called BCR/ABL (philadephia chromosome), or PDGFRA and PDGRFRB. For more information about these gene changes, see How is CMML diagnosed?

Because CMML patients have abnormal-looking (dysplastic) cells in their bone marrow, for a long time CMML was considered a type of myelodysplastic syndrome. Still, it didn't fit in well with other diseases in that group because a key feature of myelodysplastic syndromes is having too few blood cells.

CMML is more like a myeloproliferative disease (myelo -- bone marrow, proliferative -- excessive growth). Chronic myeloid leukemia is an example of a myeloproliferative disease where there's an over-production of white blood cells.

Since CMML has features of both a myelodysplastic syndrome and myeloproliferative disorder, experts created a new category for it: myelodysplastic/myeloproliferative diseases. CMML is the most common disease in this group. Much less common diseases in this group are atypical chronic myeloid leukemia and juvenile myelomonocytic leukemia. All of these diseases produce a lot of abnormal blood cells.

Genetics

Research on the causes, diagnosis, and treatment of chronic myelomonocytic leukemia (CMML) is being done at many cancer research centers. Scientists are making progress in understanding which changes in a person's DNA and RNA can cause normal bone marrow cells to develop into leukemia cells.

Studies have found that changes in the structure or activity of certain genes in CMML cells may help predict patients’ outcomes and how likely they are to go on to develop acute leukemia. Research continues in this area, and someday, this information may help guide treatment decisions.

As more information from this research unfolds, it may be used in designing new drugs or developing gene therapy. This approach replaces the abnormal DNA of cancer cells with normal DNA to restore normal control of cell growth.

Chemotherapy

Studies are in progress to find the best combination of chemotherapy drugs while trying to limit side effects. New drugs are continually being developed and tested.

As researchers have learned more about what makes cancer cells different from normal cells, they've begun to develop drugs that target these differences. Studies are looking at targeted therapies to treat CMML. These therapies target things like specific cell signaling pathways to shut down cancer cell growth. Some of these drugs are already being used to treat other cancers.

Stem cell transplant

Scientists continue to refine this procedure so that it works better and causes fewer problems. They are also looking at which patients will benefit the most and how newer transplant methods might be used to treat CMML.

If signs and symptoms suggest you may have chronic myelomonocytic leukemia (CMML), the doctors will look at cells from your blood and bone marrow to confirm this diagnosis.

Blood tests

The complete blood count (CBC) measures different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. The CBC is often done with a differential count (or “diff”), which is a count of the different types of white blood cells in the blood sample. In a blood smear, some of the blood is put on a slide to see how the cells look under the microscope.

People with CMML have higher numbers of monocytes, (at least 1,000 per mm³). Sometimes they have low numbers of other white blood cells. They may have shortages of red blood cells and blood platelets, as well.

Some patients have a small number of monoblasts in the blood. Monoblasts are the early, immature cells that grow and divide to make mature monocytes. Normally, these cells are only found in the bone marrow. It's never normal to see blasts in the blood, and it's often a sign of a bone marrow problem.

Blood cells from CMML patients may also have certain changes in size, shape, or other features that can be seen under the microscope. Blood abnormalities may suggest CMML, but an exact diagnosis cannot be made without looking at and testing cells taken from the bone marrow.

Other blood tests may be done to check for other possible causes of low blood counts, such as low levels of vitamin B12 and folate. Tests may also be done to look for other causes of a high white blood cell count, such as an infection.

Bone marrow tests

Samples of your bone marrow are taken by bone marrow aspiration and biopsy for testing. The samples are usually taken from the back of the pelvic (hip) bone. These tests are used to diagnosis and classify the type of blood cancer you have. They may be repeated later to see if treatment is working or to see if the CMML is transforming into an acute leukemia.

For bone marrow aspiration, you lie flat on a table (either on your side or on your belly). After cleaning the skin over the hip, the surface of the bone is numbed with local anesthetic. A very thin needle is used to put in the numbing drug, which may cause a brief stinging or burning sensation. A long, hollow needle is then put into the bone and a syringe is used to suck out a small amount of liquid bone marrow (about 1 teaspoon). Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done right after the aspiration. A small core of bone and marrow (about 1/16 inch in diameter and 1/2 inch long) is removed with a wider needle that's twisted as it's pushed into the hip bone. The biopsy may also cause some brief pain. Once the biopsy is done, pressure will be held to help prevent bleeding and bruising.

A pathologist (a doctor specializing in the diagnosis of diseases using laboratory tests) examines the bone marrow samples under a microscope. A hematologist (a doctor specializing in medical treatment of diseases of the blood and blood-forming tissues) or an oncologist (a doctor specializing in medical treatment of cancer) usually looks at the samples too.

Looking at the cells in the bone marrow

The doctors will look at the types and number of blood-forming cells in the bone marrow aspirate and biopsy. They will also check to see if the bone marrow shows signs of infections, cancer cells, or other disorders. They will examine the size and shape of the cells and determine whether the red cells contain iron particles or the other cells contain granules (microscopic collections of enzymes and other chemicals that help white blood cells to fight infections).

Measuring blasts

Tests will be done to measure the percentage of marrow cells that are blasts. This is very important. Blasts are very early (immature) cells that are madeby bone marrow stem cells. Over time, blasts mature into normal blood cells. But in CMML, some of the blasts do not mature properly, so there may be too many blasts and not enough mature cells. For a diagnosis of CMML, there must be less than 20% blasts in the bone marrow. A patient who has more than 20% blasts in the bone marrow has acute leukemia.

Cytogenetic tests

This test looks at the chromosomes inside the cells. DNA in human cells is packed into chromosomes. Each cell should have 46 chromosomes (23 pairs). Chromosome changes or abnormalities are fairly common in CMML. Sometimes pieces of chromosomes or even whole chromosomes are missing. CMML cells may also have extra copies of all or part of some chromosomes. Chromosome translocations may also be seen. This is where parts of chromosomes trade places with each other.

Chromosome testing can also help the doctors be sure that the problem isn’t a different leukemia, called chronic myeloid leukemia or CML. The leukemia cells in CML often contain an abnormal chromosome caused by a certain translocation. This is called the Philadelphia chromosome or BCR/ABL fusion. If the Philadelphia chromosome is present, the diagnosis is CML, not CMML. CMML also does not have changes in certain genes, called PDGFRA and PDGFRB. If these changes are present the problem might be a different myeloproliferative disorder.

Cytogenetic testing can take several weeks because the bone marrow cells need time to grow in laboratory dishes before the chromosomes can be seen with a microscope. The results of cytogenetic testing are written in a way that describes which chromosome changes are present. For instance:

• A minus sign (-) or the abbreviation "del" is used to mean a deletion. So, if a copy of chromosome 7 is missing, it can be written as -7 or del(7). Often, only a part of the chromosome is lost. There are 2 parts to a chromosome, called p and q. So the loss of the q part of chromosome 20 is called 20q- or del(20q).
• A plus sign (+) is used when there is an extra copy of all or part of a chromosome. For example, +8 means that chromosome 8 has been duplicated and too many copies of it are in the cell.
• The letter "t" is used to indicate a translocation, which is when a piece of one chromosome breaks off and becomes part of another chromosome.

Other tests

These are other bone marrow tests that help the doctor diagnose CMML and rule out other blood diseases:

• Immunocytochemistry. This testing is helpful in distinguishing CMML from other types of leukemia and from other diseases.
• Flow cytometry. This test isn't needed for all patients, but it can be very helpful in diagnosing leukemia and lymphoma.
• Molecular genetic tests. These tests are not needed to diagnose CMML, but they may be used in some cases

These tests can be done on cells besides bone marrow cells, such as cells from the blood.

Doctors often group cancers into different stages based on the size of the tumor and how far the cancer has spread from the original site in the body. The stage of a cancer can help predict the outlook for a cancer. Often, the stage of a cancer is used to decide which treatment is needed.

Chronic myelomonocytic leukemia (CMML) is a disease of the bone marrow. It cannot be staged by looking at the size of a tumor like some other cancers. Instead, CMML is split into 2 groups based on cell counts in the blood and bone marrow:

• CMML-1: Blasts make up less than 5% of white cells in the blood and less than 10% of the cells in the bone marrow.
• CMML-2: Blasts make up 5% to 20% of the white cells in the blood, or they make up 10% to 20% of the cells in the bone marrow.

The most common sign of chronic myelomonocytic leukemia (CMML) is having too many monocytes (seen on a blood test).

Having too many monocytes also causes many of the symptoms of CMML. These monocytes can settle in the spleen or liver, enlarging these organs. An enlarged spleen (called splenomegaly) can cause pain in the upper left part of the belly (abdomen). It can also cause people to notice they feel full too fast when they eat. If the liver gets too big (called hepatomegaly), it causes discomfort in the upper right part of the abdomen.

Low numbers of other types of blood cells cause many of the signs and symptoms of CMML:

• A shortage of red blood cells (anemia) can lead to feeling very tired, with shortness of breath and pale skin.
• Not having enough normal white blood cells (leukopenia) can lead to frequent or severe infections.
• A shortage of blood platelets (thrombocytopenia) can lead to easy bruising and bleeding. Some people notice frequent or severe nosebleeds or bleeding from their gums.

Other symptoms can include weight loss, fever, and loss of appetite. Of course, many of these problems are caused more often by something other than cancer. If you're having symptoms, you should see a doctor so a cause can be found.

Surgery is rarely used to treat chronic myelomonocytic leukemia (CMML). Sometimes, though, surgery to remove the spleen may be an option if the patient is having problems from an enlarged spleen. Like all surgery, this has risks related to anesthesia and wound infection. Also, since the spleen helps protect against infection, removing it can increase the risk of severe infections. If you are considering having your spleen removed, discuss the risks and benefits with your doctor.

General information about surgery in the treatment of cancer can be found in Cancer Surgery.

Chemotherapy (chemo) is the use of drugs for treating a disease such as cancer. The drugs can be swallowed as pills, or a needle can be used to inject them into a vein or muscle. Chemo is considered systemic treatment because these drugs enter the bloodstream and reach most areas of the body. This type of treatment is useful for diseases like chronic myelomonocytic leukemia (CMML) that are not only in one part of the body. Chemo cannot cure CMML, but it can help kill the abnormal bone marrow cells and allow normal ones to grow back.

Hydroxyurea

Hydroxyurea (hydroxycarbamate, Hydrea^®) is a chemo drug that has helped some patients with CMML live longer. This drug comes as a capsule that's taken by mouth daily. It can bring the numbers of white blood cells and monocytes down to normal. It may also help shrink an enlarged spleen. Because the main effect of hydroxyurea is to lower blood counts, anyone taking this drug will have their blood counts checked regularly. Other side effects are usually mild and easily tolerated. Some patients have stayed on this drug for years without problems.

Hypomethylating agents

These drugs are affect the way genes are controlled. Examples of this type of drug include azacytidine (Vidaza^®) and decitabine (Dacogen^®). Azacytidine is given as a shot under the skin or into your blood (IV) for 7 days in a row every month. Decitabine is given into your blood (IV), either once every 8 hours for 3 days, or once a day for 5 days. These drugs have been studied best in treating myelodysplastic syndromes, where they seem to help stop abnormal cells in the bone marrow from dividing to make new cells. This lets the normal cells grow again, often leading to improved blood counts and less need for transfusions. Fewer patients with CMML have been treated with these drugs in studies, but they had similar benefits in terms of blood counts.

Side effects are usually mild and rarely lead to stopping treatment. Still, these drugs can have some of the same side effects as regular chemotherapy, including:

• Nausea/vomiting
• Diarrhea
• Fatigue and weakness
• Low blood counts (most often the white blood cells or platelets)

Conventional chemotherapy

For a long time, CMML was grouped with myelodysplastic syndromes, and so it was treated with the same chemo drugs. Some of the chemo combos that have been used include:

• Cytarabine (ara-C) with idarubicin
• Cytarabine with topotecan
• Cytarabine with fludarabine

Sometimes, topotecan is given by itself.

This type of treatment can help some patients, but it can cause severe side effects, including life-threatening infections ror other problems. Using lower doses of chemo drugs.is an appoach that can help lower the chance of serious side effects. This treatment is generally only used in young and otherwise healthy people with CMML. Most patients with CMML are older and have other health problems. They are less likely to benefit from this intense type of chemo. Still, this may be an option for some people with advanced CMML.

Chemo drugs can cause many side effects. The side effects depend on the type and dose of the drugs that are given and the how long they are taken. Common side effects include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Low blood counts

Chemo often slows blood cell production. In CMML, this problem is usually made worse before it gets better. It can lead to:

• Less ability to fight infection (low white blood cell counts)
• Easy bruising and bleeding (low platelet counts)
• Fatigue (low red blood cell counts)

When platelet counts get very low, patients may need platelet transfusions to prevent or stop bleeding. Likewise, fatigue caused by low red blood cell counts can be treated with red blood cell transfusions.

Most side effects are short-term and will go away over time after treatment ends. Your health care team often can suggest ways to lessen side effects. For example, other drugs can be given along with the chemo to prevent or reduce nausea and vomiting.

Chemo drugs can also damage organs such as the kidneys, liver, testes, ovaries, brain, heart, and lungs. With careful monitoring, such side effects are rare. If serious side effects do occur, the chemo treatments may have to be reduced or stopped, at least for a short time.

Carefully monitoring and adjusting drug doses are important because some of these side effects can be permanent.

See Chemotherapy for more information.

Chronic myelomonocytic leukemia (CMML) is rare, only occurring in 4 of every million people in the United States each year. That works out to about 1,100 cases each year.

This disease is rare in young people. Almost 9 of 10 of cases are diagnosed in people 60 and older. CMML occurs more often in men than in women.

Visit the American Cancer Society’s Cancer Statistics Center for more key statistics.

A risk factor is anything that changes your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for lung cancer and many other cancers. But people without any risk factors can still get the disease. And having a risk factor, or even several, does not mean that you will get the disease. Because chronic myelomonocytic leukemia (CMML) is rare, it has been hard to study. For a long time it was grouped with myelodysplastic syndromes. As a result, only a few risk factors are known for this disease.

Age

The risk of CMML increases with age. This disease is rare in those younger than 40, with most cases found in people 60 and older.

Sex

CMML is about twice as common in men as in women.

Cancer treatment

Prior treatment with chemotherapy seems to increase the risk of CMML. The risk of CMML after cancer chemotherapy, however, is not as high as the risk of other blood problems, such as myelodysplastic syndromes and acute myeloid leukemia. Second Cancers in Adults has more information on this.

Some cases of chronic myelomonocytic leukemia (CMML) are linked to cancer treatment, but in most cases the cause is unknown.

Over the past few years, scientists have made progress in understanding how certain changes in the DNA of bone marrow cells may cause CMML to develop. DNA is the chemical that carries the instructions for nearly everything our cells do. We usually look like our parents because they are the source of our DNA. However, DNA affects more than the way we look.

Some genes (parts of DNA) control a cell’s growth and division process. Genes that promote cell division are called oncogenes. Other genes called tumor suppressor genes can slow down cell division or even make cells die at an appropriate time. Cancers can be caused by DNA mutations (gene defects) that turn on oncogenes or turn off tumor suppressor genes.

In some diseases, mutations may be passed down from a parent. Inherited mutations do not seem to cause CMML. Instead, the mutations are acquired during the person’s lifetime. Exposure to radiation or cancer-causing chemicals can cause mutations that lead to CMML. Sometimes these gene changes occur for no apparent reason. Every time a cell prepares to divide into 2 new cells, it must copy its DNA. This process is not perfect, and copying errors can occur. Fortunately, cells have repair enzymes that read and fix DNA. However, some errors may slip past, especially if the cells are growing rapidly.

Human DNA is packaged in 23 pairs of chromosomes. In up to half of patients, CMML cells contain altered chromosomes. Sometimes part of one chromosome attaches to a different chromosome. This is called a translocation. Like mutations, translocations can turn on oncogenes or turn off tumor suppressor genes. Acquired translocations are seen in some cases of CMML. Another chromosome abnormality that can be seen in CMML is called a deletion. This involves the loss of all or part of a chromosome. Another type of chromosome abnormality is called a duplication. This is when there is an extra copy of all or part of a chromosome.

It is important to have frank, open, and honest discussions with your doctor about your condition. Your doctor and the rest of the health care team want to answer all of your questions. For instance, consider these questions:

• What are my treatment choices?
• Which treatment, if any, do you recommend, and why?
• Do the treatments you recommend have side effects?
• How can I help reduce the treatment side effects I might have?
• What is the outlook for my survival?
• Should I get a second opinion, and who do you recommend as an expert in this disease?