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Cancer Medicine :: Leukemia - Chronic Myelomonocytic

Leukemia - Chronic Myelomonocytic (CMML)

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.

Treatment for CMML may include: Supportive therapy, Chemotherapy, Growth factors, Radiation therapy, Surgery, Stem cell transplant

Supportive therapy for the patient with chronic myelomonocytic leukemia

For many patients with chronic myelomonocytic leukemia (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. 

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 usually seen only in people who receive many transfusions over a period of years. Drugs called chelating agents (substances that bind with iron 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. It has been used more for patients with certain congenital anemias (like thalassemia), but 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), urinary infection (burning when urinating), or other symptoms of an infection. Doctors will treat any known or suspected infections with antibiotics.

Chemotherapy for chronic myelomonocytic leukemia

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. 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 such as chronic myelomonocytic leukemia (CMML) that are not localized to one part of the body. The purpose of the chemo is to eliminate the abnormal bone marrow 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 chemo. 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 chemo drugs. This approach can lower the chance of serious side effects.

Chemo 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)

Fatigue (due to low red blood cell counts).

When platelet counts get very low, patients may receive 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 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 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 occur, the chemo 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 chemo 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 chemo that affects the way genes are controlled. Examples of this type of drug include azacytidine (Vidaza®) and decitabine (Dacogen®). These drugs have been studied best in the treatment of myelodysplastic syndromes, where they seem to help stop abnormal cells in the bone marrow from dividing to make new cells. This allows the normal cells to grow again, often leading to improved blood counts and less need for transfusions. Fewer patients with CMML were 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, but 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)

Growth factors for the treatment of chronic myelomonocytic leukemia

Hematopoietic growth factors are hormone-like substances that stimulate bone marrow to produce blood cells. These substances occur naturally in the body, but 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 chronic myelomonocytic leukemia (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.

Radiation therapy for chronic myelomonocytic leukemia

Radiation therapy is treatment with high-energy rays or particles to destroy cancer cells. The most common form of radiation therapy, external beam radiation therapy, aims x-rays from a machine outside the patient’s body. The treatment is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Before your treatments start, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Each treatment lasts only a few minutes, but the setup time -- getting you into place for treatment -- usually takes longer.

If someone who has chronic myelomonocytic leukemia (CMML) is having problems from a very enlarged spleen, radiation therapy may be used to shrink it. Shrinking the spleen can improve symptoms like abdominal (belly) pain and trouble eating, but there are some risks. Treating the spleen with radiation leads to it not working as well. Since the spleen helps protect against infection, this can increase the risk of severe infections. If you are considering treatment with radiation for an enlarged spleen, you should talk about the risks and benefits with your doctor. You may also need to get certain vaccines before radiation starts.

Surgery for chronic myelomonocytic leukemia

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 surgeries, 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.

Stem cell transplant for chronic myelomonocytic leukemia

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: Many elderly patients 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. This type of transplant has fewer side effects, but 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

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.

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

Other side effects may occur over time: 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, Bone damage (called avascular necrosis or aseptic necrosis) occurs rarely. The bone of the hip joint is affected most often. If it becomes severe, the joint may need to be replaced. 

General approach to treatment of chronic myelomonocytic leukemia

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, CMML is not curable. In that case, the goal is to relieve symptoms while avoiding the complications and reducing side effects of treatment. Supportive care, such as transfusions, blood cell growth factors, and antibiotics to treat infections, may be given to all patients.

If treatment is needed, either of the drugs azacytidine (Vidaza) or decitabine (Dacogen) is often the first choice for CMML. Azacytidine is given by injection under the skin for 7 days in a row every month. Decitabine is also given as an injection, either once every 8 hours for 3 days, or once a day for 5 days. These drugs may cause a drop in blood counts for a time after treatment is started. Then, if the drug is successful, blood counts rise to levels above those seen before chemotherapy was started.

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 drugs 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. It can also shrink the size of the spleen to help the patient feel more comfortable.

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. Learning to live with cancer that does not go away can be difficult and very stressful. 

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 or 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. You will not want to have to worry about paying for it. Many people have been bankrupted by medical costs.

If treatment for chronic myelomonocytic leukemia stops 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. But after many different treatments, the cancer may no longer respond well to treatment. If this happens, it’s important to weigh the possible limited benefits of a new treatment against the possible downsides. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer -- when you have been through many medical treatments and nothing’s working anymore. Your doctor may offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor may say that more chemo or radiation might have about a 1% chance of working. Some people are still tempted to try this. But it is important to think about and understand your reasons for choosing this plan.

No matter what you decide to do, you need to feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose - the main purpose of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve bone pain caused by cancer that has spread to the bones. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can’t have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. You can learn more about hospice in our document called Hospice Care.

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 and RNA can cause normal bone marrow cells to develop into leukemia cells.

Recent studies have found that changes in the structure or activity of certain genes in CMML cells may help predict patients’ prognosis and how likely the patient is to develop acute leukemia. This information may eventually be used to help guide treatment decisions.

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. An oral (by mouth) form of azacitidine is being 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.

Staying hopeful is important, too. 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. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now 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. Though the cancer may be beyond your control, there are still choices you can make.

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