Leukemia -- Chronic Myelomonocytic

What is cancer?

The body is made up of hundreds of millions of living cells. Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries.

Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells.

Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell.

Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA gets damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesn't die like it should. Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first cell does.

People can inherit damaged DNA, but most DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment. Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found.

In most cases the cancer cells form a tumor. Some cancers, like leukemia, rarely form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow.

Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors that replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body.

No matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has spread to the liver is still called breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer.

Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer.

Not all tumors are cancerous. Tumors that aren't cancer are called benign. Benign tumors can cause problems – they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they can't invade, they also can't spread to other parts of the body (metastasize). These tumors are almost never life threatening.

What is chronic myelomonocytic leukemia?

Normal bone marrow

Bone marrow is found inside certain bones such as the skull, shoulder blades, ribs, pelvis, and spine. It is 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. It can cause people to appear pale and feel tired and weak. Severe anemia can cause shortness of breath.

White blood cells (also known as leukocytes) are important in defending the body against infection. The 2 major types of white blood cells are lymphocytes and granulocytes.

Lymphocytes are immune cells that are found in the bone marrow, the blood, and in lymph nodes. They make the antibodies that help the body fight germs. They can also directly kill invading germs by producing toxic substances that damage the cells.

Granulocytes are a group of white blood cells that destroy bacteria. They are called granulocytes because they contain granules that can be seen under the microscope. These granules are made up of enzymes and other substances that 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; this cell 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 also belong in the granulocyte family. They also help protect the body against bacteria. The early cells in the bone marrow that turn into monocytes are called monoblasts. When monocytes leave the bloodstream and go into tissue, they become macrophages. Macrophages can destroy germs by surrounding and digesting them. They are also important in helping lymphocytes to recognize germs and begin producing antibodies to fight them.

The third type of blood cell, platelets, are thought of as a type of blood cell, but they are actually small pieces of a cell. They start as a large cell in the bone marrow cell called the megakaryocyte. Pieces of this cell break off and enter the bloodstream as platelets. Platelets are needed for your blood to clot. They plug up damaged areas of blood vessels caused by cuts or bruises. A shortage of platelets, called thrombocytopenia, can result in excessive bleeding and bruising.

Chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia (CMML) is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood. In CMML, patients have an elevated number of monocytes in the blood, with a monocyte count of at least 1,000 (per mm3). Often, the monocyte count is much higher, causing the total white blood cell count to become very high as well. Usually there are abnormal cells in the bone marrow, but the amount of blasts (very early/immature cells) is below 20%. Many patients have enlarged spleens (an organ that lies just below the left rib cage). About 15% to 30% of patients go on to develop acute myeloid leukemia.

Because CMML patients have abnormal looking (dysplastic) cells in their bone marrow, for a long time CMML was considered to be a type of myelodysplastic syndrome. Still, it didn't fit in well with other diseases in that category. That is because the major problem in myelodysplastic syndrome is having too few blood cells.

Patients with CMML may have shortages of some blood cells, but a main problem is too many of a certain type of white blood cell (the monocyte). In this way CMML is more like a myeloproliferative disease (myelo -- bone marrow, proliferative -- excessive growth). Chronic myeloid leukemia is an example of a myeloproliferative disease where the problem is an overproduction of white blood cells. Since CMML has features of both 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.

What are the key statistics about chronic myelomonocytic leukemia?

About 1,000 to 1,500 cases of chronic myelomonocytic leukemia (CMML) are diagnosed each year in the United States. This disease is rare in young people. More than 90% of cases diagnosed in people over 60. CMML occurs slightly more often in men than in women.

What are the risk factors for chronic myelomonocytic leukemia?

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 cancer of the lung and many other cancers. But risk factors don't tell us everything. 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 syndrome. 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 over 60.

Sex

CMML is more common in men.

Cancer treatment

Prior treatment with chemotherapy seems to increase the risk of CMML. The risk of CMML after cancer chemotherapy is not as high as the risk of other blood problems, such as myelodysplastic syndrome and acute myeloid leukemia.

Do we know what causes chronic myelomonocytic leukemia?

Although some cases of chronic myelomonocytic leukemia (CMML) are linked to cancer treatment, 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) contain instructions for controlling a cell's growth and division process. Certain genes that promote cell division are called oncogenes. Other genes called tumor suppressor genes can slow down cell division or even cause cells to 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.

Can chronic myelomonocytic leukemia be prevented?

Since most cases of chronic myelomonocytic leukemia (CMML) have no known cause, this disease can rarely be prevented.

Treating cancer with chemotherapy and radiation may cause CMML. Doctors are studying ways to minimize the risk of CMML developing in patients receiving these treatments. In some cancers, doctors may try to avoid using the chemotherapy drugs that are more likely to lead to CMML. For certain cancers, however, these drugs may be needed. Often, the obvious benefits of treating life-threatening cancers with chemotherapy and radiation therapy must be balanced against the small chance of developing CMML several years later.

How is chronic myelomonocytic leukemia diagnosed?

Signs and symptoms

Some of the symptoms of chronic myelomonocytic leukemia (CMML) are caused by the high number of monocytes in the blood. These monocytes can settle in the spleen or liver, causing these organs to enlarge. An enlarged spleen (called splenomegaly) can cause pain in the upper left part of the abdomen. It can also cause people to complain of feeling full too fast when they eat. If the liver gets too large (called hepatomegaly), it mainly causes discomfort in the upper right part of the abdomen.

Shortages of certain 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 problems with easy bruising and bleeding. Some people notice frequent or severe nosebleeds or bleeding from the gums.

Other symptoms can include weight loss, fever, and loss of appetite. Of course, these problems occur not only with CMML but are more often caused by something other than cancer.

Tests to diagnose chronic myelomonocytic leukemia

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 cell counts and blood cell examination

The complete blood count (CBC) is a test that 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 (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.

Patients with CMML have higher numbers of monocytes, with a monocyte count of at least 1,000/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 may 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 is never normal to see blasts in the blood, and it often signals a bone marrow problem. Blood cells from CMML patients may also have certain abnormalities in size, shape, or other features that can be seen under the microscope.

Although blood abnormalities may suggest CMML, the doctor cannot make an exact diagnosis without examining a sample of bone marrow cells.

Other blood tests

The doctor may also order tests 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 infection.

Bone marrow tests

Bone marrow samples are obtained from a bone marrow aspiration and biopsy, procedures that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone. These tests are used first for diagnosis and classification and may be repeated later to tell if the CMML is responding to therapy or is transforming into an acute leukemia.

For bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the area, the skin over the hip and the surface of the bone is numbed with local anesthetic, which may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted 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 just after the aspiration. A small piece of bone and marrow (about 1/16 inch in diameter and 1/2 inch long) is removed with a slightly larger needle that is twisted as it is pushed down into the bone. The biopsy may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.

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 reviews these as well.

The doctors will look at 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). The percentage of marrow cells that are blasts is particularly important. Blasts are very early (immature) cells that are produced by bone marrow stem cells. Blasts eventually mature into normal blood cells. 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, a patient must have less than 20% blasts in the bone marrow. A patient who has more than 20% blasts in the bone marrow is considered to have acute leukemia.

Different types of tests that are done on the bone marrow help the doctor diagnose CMML and exclude other blood diseases:

Cytochemistry: Cells from the bone marrow sample are placed on glass microscope slides and then exposed to stains (dyes) that are attracted to certain chemicals present in only certain types of cells. For example, one stain causes the granules inside the cells to appear as black spots when viewed under the microscope, but it does not cause other types of cells to change colors.

Immunocytochemistry: Cells from the bone marrow sample are treated with special antibodies that cause certain types of cells change color. The color change can be seen only under a microscope. This testing is helpful in distinguishing CMML from other types of leukemia and from other diseases.

Flow cytometry: This technique is sometimes used to examine the cells from bone marrow and blood samples. It can be very helpful in diagnosing leukemia and lymphoma. A sample of cells is treated with special antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of cells. If the sample contains those cells, the laser will cause them to give off light. The instrument detects the light, and a computer counts the cells. This test may not be needed for all patients.

Cytogenetics: This test involves looking at the chromosomes inside the cells. DNA in human cells is packed into chromosomes. Each cell should have 46 chromosomes (23 pairs). Chromosome 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 portions of chromosomes may trade places with each other.

Cytogenetic testing can take more than 3 weeks because the bone marrow cells need time to grow in laboratory dishes before their chromosomes can be viewed under the microscope. The results of cytogenetic testing are written in a shorthand form that describes which chromosome changes are present. For example:

• A minus sign (-) or the abbreviation del is used to mean a deletion. For example, 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. Thus the loss of the q part of chromosome 5 is called 5q- or del(5q).
• 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 found within 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.

Molecular genetic studies: This is another type of test that can be used to find chromosome and gene abnormalities. An example of this is fluorescent in situ hybridization, more commonly called FISH. In FISH, specific gene sequences are stained with a fluorescent dye. These may correspond to a certain area of a chromosome or even a certain translocation. An advantage of FISH is that it doesn't require actively dividing cells. This allows the testing to go a bit faster. FISH is very good for finding translocations; it can even find some that may be too small to be seen with usual cytogenetic testing. This test is not needed to make a diagnosis of CMML, but it may be used in some cases.

How is chronic myelomonocytic leukemia staged?

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.

However, 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

Survival rates for chronic myelomonocytic leukemia

Survival rates are often used by doctors as a standard way of discussing a person's prognosis (outlook). Some patients with cancer may want to know the survival statistics for people in similar situations, while others may not find the numbers helpful, or may even not want to know them. Whether or not you want to read about the survival statistics below for CMML cancer is up to you.

There are several ways to describe a person's prognosis likely prognosis. The 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. Of course, many people live much longer than 5 years (and many are cured). Also, some people die from causes other than their cancer.

Median survival is the amount of time for half the patients in the group to die. This is a middle value -- half the patients live longer than this, and half do not live this long. Median survival is another standard way to indicate outlook.

In order to get 5-year survival rates or median survival estimates, doctors have to look at people who were treated several years ago. Improvements in treatment since then may result in a more favorable outlook for people now being diagnosed with CMML.

Survival rates and median survival estimates are based on previous outcomes of large numbers of people who had the disease, but they cannot predict what will happen in any particular person's case. Many other factors may affect a person's outlook, such as overall health and age. Your doctor can tell you how the numbers below may apply to you, as he or she is familiar with the aspects of your particular situation.

Patients with CMML-1 tend to live longer than those with CMML-2. In one study of CMML patients diagnosed between 1975 and 2005, the median survival times with CMML-1 and CMML-2 were 20 months and 15 months, respectively. However, some patients lived much longer. About 20 percent of CMML-1 patients and about 10 percent of CMML-2 patients survived longer than 5 years. Also, patients with CMML-2 are more likely to go on to develop acute leukemia than patients with CMML-1. In the same study, 18 percent of CMML-1 patients and 63 percent of CMML-2 patients developed acute myeloid leukemia within 5 year of their CMML diagnosis.

In addition to the type of CMML, other factors may be helpful in predicting survival. These include blood cell counts, certain chromosome changes, and blood levels of LDH (lactate dehydrogenase).

How is chronic myelomonocytic leukemia treated?

General treatment information

Treatment of chronic myelomonocytic leukemia (CMML) is based on how severe the disease is, as well as the patient's age and health. Patients with CMML are treated by specialists such as hematologists or oncologists.

Supportive therapy

For many patients with CMML, the main goal of treatment is to prevent the problems caused by low blood cell counts. For example, low red blood cell counts (anemia) can cause severe fatigue. Treating the anemia with red blood cell transfusions and/or erythropoietin can help patients feel better and allow them to be more active. (More information about erythropoietin can be found in the section, "Growth factors.")

Although some people are concerned about a slight risk of infection (hepatitis or HIV) spread by blood transfusion, this possibility is very unlikely, and the benefits of the transfused cells greatly outweigh this risk.

Blood transfusions can cause excess iron to build up in the body. This extra iron can deposit in the liver and heart, causing the organs to function poorly. This iron build up is only seen in people who receive many transfusions over a period of years. Drugs called chelating agents (substances that bind with metal so that the body can get rid of it) can be used to treat and prevent iron overload from transfusions. The most commonly used drug is desferoxamine. This drug can be given intravenously or as an injection under the skin. It is inconvenient because the injection must be given slowly (over several hours) 5 to 7 times per week. In some patients, treatment continues for years. Deferasirox (Exjade^®) is a newer drug that is taken by mouth once a day to treat iron overload. Although it has been used more for patients with certain congenital anemias (like thalassemia), it can also be used to treat iron overload in patients with CMML.

CMML patients with bleeding problems resulting from a shortage of platelets may benefit from platelet transfusions.

Patients with CMML are susceptible to infections. They should be especially careful to avoid cuts and scrapes and to care for any that occur right away. They should tell their doctors immediately about any fever, signs of pneumonia (cough, shortness of breath), or urinary infection (burning when urinating). Doctors will treat any known or suspected infections with antibiotics.

Chemotherapy

Chemotherapy (chemo) is the use of drugs for treating a disease such as cancer. The drugs can be swallowed as pills, or they can be injected by needle into a vein or muscle. Chemotherapy 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 such as CMML that are not localized to one part of the body. The purpose of the chemotherapy is to eliminate the abnormal stem cells and allow normal ones to grow back.

Conventional chemotherapy

CMML can progress to acute leukemia, and some patients are treated with the same type of chemotherapy. Some of the chemo drugs that have been used include cytarabine with idarubicin, cytarabine with topotecan, and cytarabine with fludarabine. This type of treatment can help some patients, but it is very toxic. Side effects can be severe, and may even hasten death. This treatment is generally only used in CMML patients that are young and otherwise healthy. 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 patients with advanced CMML.

Another option is to use lower doses of chemotherapy drugs. This approach can lower the chance of serious side effects.

Chemotherapy drugs can cause many side effects. The side effects depend on the type and dose of the drugs that are given and the length of time they are taken. Common side effects include:

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

Chemotherapy often slows blood production, leading to low blood counts. In CMML, this problem is usually made worse before it gets better. It can lead to lowered resistance to infection (due to low white blood cell counts), easy bruising and bleeding (due to low platelet counts), and fatigue (due to low red blood cell counts).

While platelet counts are low, patients may receive platelet transfusions as protection against bleeding. Likewise, fatigue caused by low red blood cell counts can be treated with red blood cell transfusions.

Most side effects are temporary and will go away after treatment is finished. Your health care team often can suggest ways to lessen side effects. For example, other drugs can be given along with the chemotherapy to prevent or reduce nausea and vomiting.

Chemotherapy 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 occur, the chemotherapy treatments may have to be reduced or stopped, at least temporarily.

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

Hydroxyurea

Hydroxyurea (hydroxycarbamate, Hydrea^®) is a chemotherapy drug that has helped some patients with CMML live longer. This drug comes as a capsule and is taken by mouth daily. It can lower the counts of white blood cells and monocytes to normal. It may also help shrink the spleen when it is enlarged. 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 ill effects.

Hypomethylating agents

These drugs are actually a form of chemotherapy that affects the way genes are controlled. Examples of this type of drug include azacytidine (Vidaza^®) and decitabine (Dacogen^®).When given to patients with CMML, they help stop the abnormal cells from dividing to make new cells. This allows the normal cells to grow again, often leading to improved blood counts. White blood cell counts may go back to normal and red blood cell counts may improve enough to stop transfusions.

These drugs 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)

Side effects are usually mild and rarely lead to stopping treatment.

Growth factors

Hematopoietic growth factors are hormone-like substances that stimulate bone marrow to produce blood cells. Although these substances occur naturally in the body, scientists have found a way to make them outside of the body in large amounts. This allows patients to receive these factors in larger doses than would be produced by their own body.

Shortages of blood cells cause many of the symptoms in people with CMML, and growth factors can help the blood counts become more normal.

Erythropoietin (Epo^® or Procrit^®), a growth factor that promotes red blood cell production, can help avoid transfusions of red blood cells in some patients. Recently it has been found that combining erythropoietin with a growth factor for white blood cells (G-CSF, Neupogen^®, or filgrastim) improves the patient's response to the erythropoietin. Darbepoetin (Aranesp^®) is a long-acting form of erythropoietin. It works in the same way but can be given less often.

A drug called oprelvekin (Neumega^®, interleukin-11, or IL-11) can be used to stimulate platelet production after chemotherapy and in some other diseases. This drug can help increase the platelet counts of some CMML patients for a time, but then the counts go back down again. For most patients, this drug is not very helpful.

More studies are underway to find the best way to predict which patients will benefit from growth factors and the best way to combine growth factors with each other and with other treatments, such as chemotherapy or hormones. Patients usually receive the growth factors through subcutaneous (under the skin) injections. Your health care team can give the injections, or you or your family members can learn to give them.

Stem cell transplant

Stem cell transplant (SCT) in the only treatment that can cure CMML. In this treatment, the patient receives high-dose chemotherapy and/or total body irradiation to kill the cells in the bone marrow (including the abnormal bone marrow cells). Then the patient receives new, functioning blood-forming stem cells. There are 2 main types of SCT: allogeneic and autologous.

Autologous transplant

In an autologous stem cell transplant, after the bone marrow is destroyed, the patient is given back their own stem cells. This type of transplant is not a standard treatment for patients with CMML because their bone marrow contains abnormal stem cells.

Allogeneic transplant

For an allogeneic stem cell transplant, the patient receives blood-forming stem cells from a donor. The donor's cells must be matched to the patient's cell type. The best results are seen when the donor is related to the patient, such as a brother or sister. Less often, the donor is matched to the patient, but is not related. Donor stem cells can be taken from multiple bone marrow samples, but more often are taken from the peripheral (circulating) blood by a method known as apheresis. Allogeneic SCT can have serious, even fatal, side effects. It is used most often in younger patients without serious health problems. It is rarely used in elderly patients.

Non-myeloablative transplant: Most patients over the age of 55 can't tolerate the high doses of chemotherapy needed for a standard allogeneic transplant. Some older patients may be able to have a non-myeloablative transplant (also known as a mini-transplant or reduced-intensity transplant). This is a type of allogeneic SCT that uses lower doses of chemotherapy and radiation that do not completely destroy the cells in the bone marrow. After the chemotherapy/radiation, the patient receives the donor stem cells. These cells enter the body and establish a new immune system. The new immune cells see the leukemia cells as foreign and attack them. This is called a graft-versus-leukemia effect.

The lower doses of chemotherapy and radiation involved are less toxic than what is used in a standard allogeneic transplant. This makes non-myeloablative transplant an option for older patients. Although this type of transplant has fewer side effects, some serious side effects remain, particularly graft-versus-host disease.

Side effects

Many of the side effects from a SCT are from the high doses of chemotherapy and radiation used. Some early side effects can include:

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

Other side effects may occur over time. These long-term side effects may include:

• Damage to the lungs from radiation (this is rare)
• Damage to the ovaries causes infertility and abrupt menopause, usually with symptoms such as hot flashes and loss of menstrual periods.
• Damage to the thyroid gland may produce problems with metabolism.
• Cataracts, clouding of the lens of the eye that can decrease vision, may occur.
• Joint damage (called aseptic necrosis) occurs rarely. If it becomes severe, the joint may need to be replaced

The most serious side effect from allogeneic transplants is called graft-versus-host disease (or GVHD). This occurs when the new immune cells (from the donor) see the patient's tissues as foreign and so attack them. This is more common if the donor is unrelated or if the cells aren't completely matched. GVHD can occur early in the transplant process. This is called acute GVHD. It can also start later but then last a long time; this is called chronic GVHD.

GVHD can affect the skin, where it can cause a rash, blistering, or open sores. When GVHD affects the intestines, it can cause massive diarrhea. It can also cause problems with the liver and lungs. Drugs to suppress the immune system are given as part of the transplant in order to prevent GVHD. If GVHD develops despite these drugs, additional treatments to suppress the immune system may be needed.

Although allogeneic SCT is currently the only treatment that can cure some patients with CMML, not all patients who get a transplant are cured. In addition, many patients may die from complications of this treatment.

For more information about stem cell transplants, see our document Bone Marrow & Peripheral Blood Stem Cell Transplants.

Clinical trials

You may have had to make a lot of decisions since you've been told you have cancer. One of the most important decisions you will make is choosing which treatment is best for you. You may have heard about clinical trials being done for your type of cancer. Or maybe someone on your health care team has mentioned a clinical trial to you.

Clinical trials are carefully controlled research studies that are done with patients who volunteer for them. They are done to get a closer look at promising new treatments or procedures.

If you would like to take part in a clinical trial, you should start by asking your doctor if your clinic or hospital conducts clinical trials. You can also call our clinical trials matching service for a list of clinical trials that meet your medical needs. You can reach this service at 1-800-303-5691 or on our Web site at http://clinicaltrials.cancer.org. You can also get a list of current clinical trials by calling the National Cancer Institute's Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) or by visiting the NCI clinical trials Web site at www.cancer.gov/clinicaltrials.

There are requirements you must meet to take part in any clinical trial. If you do qualify for a clinical trial, it is up to you whether or not to enter (enroll in) it.

Clinical trials are one way to get state-of-the art cancer treatment. They are the only way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

You can get a lot more information on clinical trials in our document called Clinical Trials: What You Need to Know. You can read it on our Web site or call our toll-free number (1-800-227-2345) and have it sent to you.

Complementary and alternative therapies

When you have cancer you are likely to hear about ways to treat your cancer or relieve symptoms that your doctor hasn't mentioned. Everyone from friends and family to Internet groups and Web sites may offer ideas for what might help you. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

What exactly are complementary and alternative therapies?

Not everyone uses these terms the same way, and they are used to refer to many different methods, so it can be confusing. We use complementary to refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor's medical treatment.

Complementary methods: Most complementary treatment methods are not offered as cures for cancer. Mainly, they are used to help you feel better. Some methods that are used along with regular treatment are meditation to reduce stress, acupuncture to help relieve pain, or peppermint tea to relieve nausea. Some complementary methods are known to help, while others have not been tested. Some have been proven not be helpful, and a few have even been found harmful.

Alternative treatments: Alternative treatments may be offered as cancer cures. These treatments have not been proven safe and effective in clinical trials. Some of these methods may pose danger, or have life-threatening side effects. But the biggest danger in most cases is that you may lose the chance to be helped by standard medical treatment. Delays or interruptions in your medical treatments may give the cancer more time to grow and make it less likely that treatment will help.

Finding out more

It is easy to see why people with cancer think about alternative methods. You want to do all you can to fight the cancer, and the idea of a treatment with no side effects sounds great. Sometimes medical treatments like chemotherapy can be hard to take, or they may no longer be working. But the truth is that most of these alternative methods have not been tested and proven to work in treating cancer.

As you consider your options, here are 3 important steps you can take:

• Look for "red flags" that suggest fraud. Does the method promise to cure all or most cancers? Are you told not to have regular medical treatments? Is the treatment a "secret" that requires you to visit certain providers or travel to another country?
• Talk to your doctor or nurse about any method you are thinking about using.
• Contact us at 1-800-227-2345 to learn more about complementary and alternative methods in general and to find out about the specific methods you are looking at.

The choice is yours

Decisions about how to treat or manage your cancer are always yours to make. If you want to use a non-standard treatment, learn all you can about the method and talk to your doctor about it. With good information and the support of your health care team, you may be able to safely use the methods that can help you while avoiding those that could be harmful.

General approach to treatment

Stem cell transplant (SCT) is the only way to cure patients with chronic myelomonocytic leukemia (CMML). It may be the treatment of choice for younger patients when a matched donor is available. This may also be an option for some older patients.

If SCT is not an option, the CMML is not curable. In that case, the goal is to relieve symptoms while avoiding the complications and side effects of treatment. Some of the treatments that can help with CMML symptoms include transfusions and blood cell growth factors.

Treatment with azacytidine or decitabine is often the first choice for CMML. Azacytidine is given by injection under the skin for 7 days in a row every month. The major side effect is the early drop in blood counts seen with most chemotherapy drugs. If the drug is successful, these recover to levels above those seen before chemotherapy was started. Decitabine is also given as an injection, either once every 8 hours for 3 days, or once a day for 5 days.

A major benefit for patients receiving azacytidine or decitabine is a lessened need for transfusions and an improved quality of life. In particular, if their disease responds, the patients have less fatigue and are able to function more normally. Finally, the drug may increase life span, although this isn't certain.

Treatment with hydroxyurea can help some patients who have high white blood cell counts. This drug can help lower monocyte counts and decrease the need for transfusions.

All patients receive supportive care, including transfusions and antibiotics as needed. Growth factors can also be helpful.

More treatment information

For more details on treatment options -- including some that may not be addressed in this document -- the National Comprehensive Cancer Network (NCCN) and the National Cancer Institute (NCI) are good sources of information.

The NCCN, made up of experts from many of the nation's leading cancer centers, develops cancer treatment guidelines for doctors to use when treating patients. Those are available on the NCCN Web site (www.nccn.org).

The NCI provides treatment information via Toll-free number (1-800-4-CANCER) and its Web site (www.cancer.gov). Information for patients as well as more detailed information intended for use by cancer care professionals is also available on www.cancer.gov.

What happens after treatment for chronic myelomonocytic leukemia?

General information

Since chronic myelomonocytic leukemia (CMML) is rarely cured, most patients never actually complete treatment. Patients may go through a series of treatments with rest in-between. Some people stop active treatment in favor of supportive care.

Follow-up care

Even if you have stopped treatment for your CMML, it is still very important to keep all follow-up appointments. During these visits, your doctors will ask about symptoms, do physical exams, and order blood tests. They will continue to watch for signs of infection and progression to leukemia, as well as for short-term and long-term side effects for treatment. This is the time for you to ask your health care team any questions you need answered and to discuss any concerns you might have.

Almost any cancer treatment can have side effects. Some may last for a few weeks to several months, but others can be permanent. Don't hesitate to tell your cancer care team about any symptoms or side effects that bother you so they can help you manage them.

It is also important to keep your medical insurance. With a chronic disease like CMML, your treatment may never really be over. The last thing you want is to have to worry about paying for it. Many people have been bankrupted by medical costs.

Seeing a new doctor

At some point after your cancer diagnosis and treatment, you may find yourself in the office of a new doctor. Your original doctor may have moved or retired, or you may have moved or changed doctors for some reason. It is important that you be able to give your new doctor the exact details of your diagnosis and treatment. Make sure you have the following information handy:

• A copy of your pathology report from any biopsy or surgery
• If you had surgery, a copy of your operative report
• If you were hospitalized, a copy of the discharge summary that every doctor prepares when patients are sent home from the hospital
• Finally, since some drugs can have long-term side effects, a list of your drugs, drug doses, and when you took them

Lifestyle changes to consider during and after treatment

Having cancer and dealing with treatment can be time-consuming and emotionally draining, but it can also be a time to look at your life in new ways. Maybe you are thinking about how to improve your health over the long term. Some people even begin this process during cancer treatment.

Make healthier choices

Think about your life before you learned you had cancer. Were there things you did that might have made you less healthy? Maybe you drank too much alcohol, or ate more than you needed, or smoked, or didn't exercise very often. Emotionally, maybe you kept your feelings bottled up, or maybe you let stressful situations go on too long.

Now is not the time to feel guilty or to blame yourself. However, you can start making changes today that can have positive effects for the rest of your life. Not only will you feel better but you will also be healthier. What better time than now to take advantage of the motivation you have as a result of going through a life-changing experience like having cancer?

You can start by working on those things that you feel most concerned about. Get help with those that are harder for you. For instance, if you are thinking about quitting smoking and need help, call the American Cancer at 1-800-227-2345.

Diet and nutrition

Eating right can be a challenge for anyone, but it can get even tougher during and after cancer treatment. For instance, treatment often may change your sense of taste. Nausea can be a problem. You may lose your appetite for a while and lose weight when you don't want to. On the other hand, some people gain weight even without eating more. This can be frustrating, too.

If you are losing weight or have taste problems during treatment, do the best you can with eating and remember that these problems usually improve over time. You may want to ask your cancer team for a referral to a dietitian, an expert in nutrition who can give you ideas on how to fight some of the side effects of your treatment. You may also find it helps to eat small portions every 2 to 3 hours until you feel better and can go back to a more normal schedule.

Rest, fatigue, work, and exercise

Fatigue is a very common symptom in people with CMML. This is often not an ordinary type of tiredness but a "bone-weary" exhaustion that doesn't get better with rest. For some, this fatigue lasts a long time, and it can discourage them from physical activity.

However, exercise can actually help you reduce fatigue. Studies have shown that patients who follow an exercise program tailored to their personal needs feel physically and emotionally improved and can cope better.

If you are ill and need to be on bed rest during treatment, it is normal to expect your fitness, endurance, and muscle strength to decline some. Physical therapy can help you maintain strength and range of motion in your muscles, which can help fight fatigue and the sense of depression that sometimes comes with feeling so tired.

Any program of physical activity should fit your own situation. An older person who has never exercised will not be able to take on the same amount of exercise as a 20-year-old who plays tennis 3 times a week. If you haven't exercised in a few years but can still get around, you may want to think about taking short walks.

Talk with your health care team before starting, and get their opinion about your exercise plans. Then, try to get an exercise buddy so that you're not doing it alone. Having family or friends involved when starting a new exercise program can give you that extra boost of support to keep you going when the push just isn't there.

If you are very tired, though, you will need to balance activity with rest. It is okay to rest when you need to. It is really hard for some people to allow themselves to do that when they are used to working all day or taking care of a household. (For more information about fatigue, please see our document, Fatigue in the Patient With Cancer.)

Exercise can improve your physical and emotional health.

• It improves your cardiovascular (heart and circulation) fitness.
• It strengthens your muscles.
• It reduces fatigue.
• It lowers anxiety and depression.
• It makes you feel generally happier.
• It helps you feel better about yourself.

How about your emotional health?

At some point you may find yourself overwhelmed by emotions. This happens to a lot of people.

Now you may find that you think about the potential of your own death, or the effect of your cancer on your family, friends, and career. You may also begin to re-evaluate your relationship with your spouse or partner. Unexpected issues may also cause concern. For instance, if you become healthier and have fewer doctor visits, you will see your health care team less often. That can be a source of anxiety for some.

This is an ideal time to seek out emotional and social support. You need people you can turn to for strength and comfort. Support can come in many forms: family, friends, cancer support groups, church or spiritual groups, online support communities, or individual counselors.

Almost everyone who has been through cancer can benefit from getting some type of support. What's best for you depends on your situation and personality. Some people feel safe in peer-support groups or education groups. Others would rather talk in an informal setting, such as church. Others may feel more at ease talking one-on-one with a trusted friend or counselor. Whatever your source of strength or comfort, make sure you have a place to go with your concerns.

The cancer journey can feel very lonely. It is not necessary or realistic to go it all by yourself. And your friends and family may feel shut out if you decide not to include them. Let them in -- and let in anyone else who you feel may help. If you aren't sure who can help, call your American Cancer Society at 1-800-227-2345 and we can put you in touch with an appropriate group or resource.

You can't change the fact that you have had cancer. What you can change is how you live the rest of your life -- making healthy choices and feeling as well as possible, physically and emotionally.

What happens if treatment is no longer working?

If your chronic myelomonocytic leukemia (CMML) does not improve with the first treatment, it is often possible to try something else to help you live longer and feel better. On the other hand, when a person has received several different medical treatments and nothing is helping, it's important to weigh the possible limited benefit of a new treatment against the possible downsides, including continued doctor visits and treatment side effects.

Everyone has his or her own way of looking at this. Some people may want to focus on remaining comfortable during their limited time left.

This is likely to be the most difficult time in your battle with CMML -- when you have tried everything medically within reason and it's just not working anymore. Although your doctor may offer you new treatment, you need to consider that at some point, continuing treatment is not likely to improve your health or change your prognosis or survival.

If you want to continue treatment to fight your CMML as long as you can, you still need to consider the odds of more treatment having any benefit. In many cases, your doctor can estimate the response rate for the treatment you are considering.

No matter what you decide to do, it is important that you be as comfortable as possible. Make sure you are asking for and getting treatment for any symptoms you might have, such as pain. This type of treatment is called palliative treatment.

Palliative treatment helps relieve these symptoms, but is not expected to cure the disease; its main purpose is to improve your quality of life. At some point, you may benefit from hospice care. Most of the time, this is given at home. Your CMML may be causing symptoms or problems that need attention, and hospice focuses on your comfort. You should know that receiving hospice care doesn't mean you can't have treatment for the problems caused by your cancer or other health conditions. It just means that the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult stage of your disease.

Remember also that maintaining hope is important. Your hope for a cure may not be as bright, but there is still hope for good times with family and friends -- times that are filled with happiness and meaning. In a way, pausing at this time in your treatment is an opportunity to refocus on the most important things in your life. This is the time to do some things you've always wanted to do and to stop doing the things you no longer want to do.

What should you ask your doctor about chronic myelomonocytic leukemia?

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 treatment choices do I have?
• Which treatment, if any, do you recommend, and why?
• What are the side effects of the treatments that you recommend?
• How can I help reduce the side effects I may have from the treatment?
• What is the outlook for my survival?

What's new in chronic myelomonocytic leukemia research and treatment?

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 how changes in a person's DNA can cause normal bone marrow cells to develop into leukemia cells.

As more information from this research unfolds, it may be used in designing new drugs or eventually in 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 most effective combination of chemotherapy drugs while still avoiding unnecessary side effects. New drugs are continually being developed and tested. Research is underway to determine whether patients with certain unfavorable prognostic features will benefit from more intensive chemotherapy.

Stem cell transplant

Scientists continue to refine this procedure to increase its effectiveness, reduce complications, and determine which patients are likely to be helped by this treatment.

Additional resources

More information from your American Cancer Society

We have selected some related information that might also be helpful to you. These materials may be ordered from our toll-free number (1-800-227-2345) or viewed on our Web site.

After Diagnosis: A Guide for Patients and Families (also available in Spanish)

Blood Product Donation And Transfusion

Bone Marrow & Peripheral Blood Stem Cell Transplants (also available in Spanish)

Caring for the Patient With Cancer at Home (also available in Spanish)

Infections In People With Cancer

Myelodysplastic Syndrome

Second Cancers Caused By Cancer Treatment

Understanding Chemotherapy: A Guide for Patients and Families (also available in Spanish)

The following book is available from the American Cancer Society. Call us at 1-800-227-2345 to ask about costs or to place your order.

Caregiving: A Step-By-Step Resource for Caring for the Person with Cancer at Home.

National organizations and Web sites*

In addition to the American Cancer Society, other sources of patient information and support include:

The National Marrow Donor Program
Toll-free number: 1-800-MARROW2 (1-800-627-7692)
Web site: www.marrow.org

Aplastic Anemia & MDS International Foundation, Inc.
Toll-free number: 1-800-747-2820
Web site: www.aamds.org

The Leukemia & Lymphoma Society
Toll-free number: 1-800-955-4572
Web site: www.leukemia-lymphoma.org

The Myelodysplastic Syndromes Foundation
Toll-free number: 1-800-MDS-0839
Web site: www.mds-foundation.org

National Cancer Institute
Toll-free number: 1-800-4-CANCER
TTY: 1-8---332-8615
Web site: www.cancer.gov

No matter who you are, we can help. Contact us anytime, day or night, for information and support. Call us at 1-800-227-2345 or visit www.cancer.org.

References

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Elliott MA. Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined. Best Pract Res Clin Haematol. 2006;19(3):571-593.

Faderl S, Kantarjian H. Myelodysplastic syndromes. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008:2292-2304.

Foran JM, Sekeres MA. Myelodysplastic Syndromes. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE. Kastan MB, McKenna WG, eds. Clinical Oncology. 4th ed. Philadelphia, Pa: Elsevier; 2008:2235-2259.

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Germing U, Strupp C, Knipp S, et al. Chronic myelomonocytic leukemia in the light of the WHO proposals. Haematologica. 2007 Jul;92(7):974-7.

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Jabbour E, Garcia-Manero G, Taher A, Kantarjian HM. Managing iron overload in patients with myelodysplastic syndromes with oral deferasirox therapy. Oncologist. 2009 May;14(5):489-96.

Nguyen PL, Hanson CA. Chronic Myelomonocytic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndromes. In: Steensma DP, ed. Myelodysplastic Syndromes: Pathobiology and Clinical Management, 2nd ed. New York, NY: Informa Healthcare, 2009: 285-310.

NCCN Clinical Practice Guidelines in Oncology. Myelodysplastic Syndromes. V.2.2010. Accessed at: www.nccn.org on March 8,2010.

PDQ database. Myelodysplastic/Myeloproliferative Diseases Treatment. 11/6/2008. National Cancer Institute. Accessed at www.cancer.gov/cancertopics/pdq/treatment/mds-mpd/HealthProfessional on March 2010.

Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009 Aug 10;27(23):3842-8.