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Cancer Medicine :: Leukemia - Acute Myeloid - AML Treatment

Leukemia - Acute Myeloid - AML

General treatment information

This section starts with general comments about types of treatments used for acute myeloid leukemia (AML). This is followed by a discussion of the typical treatment approach for AML. The treatment of acute promyelocytic leukemia (APL) is different from other subtypes, and is discussed separately.

As noted earlier, adult AML is not a single disease. It is really a group of related diseases, and patients with different subtypes of AML vary in their outlook and response to treatment. Treatment options for each patient are based on the subtype and lab tests of the leukemia cells, as well as certain other prognostic features .

Several types of treatment may be used in people with AML. The main treatment for AML is chemotherapy. Surgery and radiation therapy may be used in special circumstances.

In most cases AML can progress rapidly, so it is important to start treatment as soon as possible after the diagnosis is made.

Chemotherapy for acute myeloid leukemia

Chemotherapy (chemo) is the use of anti-cancer drugs that are injected into a vein, under the skin, or into the cerebrospinal fluid (CSF) or are taken by mouth to destroy or control cancer cells. Except when given into the CSF, these drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancers such as leukemia that spread throughout the body.

Doctors give chemo in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Chemo is often not recommended for patients in poor health, but advanced age by itself is not a barrier to getting chemo.

Treatment of acute myeloid leukemia (AML) is usually divided into 2 phases:

Remission induction (often just called induction)

Consolidation (post-remission therapy)

For some types of AML, there is a 3rd phase: maintenance.

Induction is the first phase of treatment. The goal is to clear the blood of leukemia cells (blasts) and to reduce the number of blasts in the bone marrow to normal.

Consolidation is chemo given after the patient has recovered from induction. It is meant to kill the small number of leukemia cells that are still around but can't be seen (because there are so few of them).

Maintenance involves giving a low dose of a chemo drug for months or years after consolidation is finished. This is often used for AML M3, but rarely used for other types of AML.

The chemo drugs used most often to treat AML are cytarabine (cytosine arabinoside or ara-C) and the anthracycline drugs (such as daunorubicin/daunomycin, idarubicin, and mitoxantrone).

Some of the other chemo drugs that may be used to treat AML include: 6-thioguanine (6-TG), Hydroxyurea (Hydrea®), Corticosteroid drugs, such as prednisone or dexamethasone (Decadron®), Methotrexate, 6-mercaptopurine (6-MP)

Possible side effects

Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemotherapy depend on the type and dose of drugs given and how long they are taken. These side effects may include: Hair loss, Mouth sores, Loss of appetite, Nausea and vomiting

Chemo drugs affect the bone marrow, which often causes low blood cell counts in AML patients. This can lead to:

Increased risk of infections (due to low white blood cell counts)

Easy bruising or bleeding (due to low blood platelets)

Fatigue (due to low red blood cells)

Most side effects are short-term and go away once treatment is finished. Low blood cell counts can last weeks, but then should return to normal. There are often ways to lessen these side effects. For example, there are drugs that can be given to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about medicines to help reduce side effects, and let him or her know when you do have side effects so they can be managed effectively.

Drugs known as growth factors, such as G-CSF (filgrastim, Neupogen®) and GM-CSF (sargramostim, Leukine®), are sometimes given to increase the white blood cell counts after chemo, to reduce the chance of infection. However, it is not clear if they have an effect on treatment success.

If your white blood cell counts are very low during treatment, you can help reduce your risk of infection by carefully avoiding exposure to germs. During this time, your doctor may tell you to:

Wash your hands often.

Avoid fresh, uncooked fruits and vegetables and other foods that might carry germs.

Avoid fresh flowers and plants because they may carry mold.

Make sure other people wash their hands when they come in contact with you.

Avoid large crowds and people who are sick (wearing a surgical mask offers protection in these situations).

Antibiotics may be given before there are signs of infection or at the earliest sign that an infection may be developing. Drugs that help prevent viral and fungal infections may also be given.

Many of the side effects of chemo are caused by low white blood cell counts. Decisions about when a patient can leave the hospital are often influenced by his or her blood counts. Some people find it helpful to keep track of their counts. If you are interested in this, ask your doctor or nurse about your blood cell counts and what these numbers mean.

If your platelet counts are low, you may be given drugs or platelet transfusions to help prevent bleeding. Likewise, shortness of breath and extreme fatigue caused by low red blood cell counts may be treated with drugs or with red blood cell transfusions.

Some possible side effects are specific to certain drugs. For example, cytarabine can cause certain problems, especially when used at high doses. These can include dryness in the eyes and effects on certain parts of the brain, which can lead to coordination and balance problems. The drug dose may need to be reduced or stopped altogether if these side effects appear. The anthracyclines can cause heart damage and so they may not be able to be used in someone who already has heart problems.

Other organs that could be directly damaged by chemo drugs include the kidneys, liver, testicles, ovaries, heart, and lungs. Doctors and nurses carefully monitor treatment to reduce the risk of these side effects as much as possible.

If serious side effects occur, the chemo may have to be reduced or stopped, at least for a short time. Careful monitoring and adjustment of drug doses are important because some side effects involving organs can be permanent.

Tumor lysis syndrome is another possible side effect of chemo. This syndrome can be seen in patients who have large numbers of leukemia cells in the body before treatment, and so mainly affects patients during the induction phase of treatment. When chemo kills these cells, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, which aren't able to get rid of all of these substances at once. Excess amounts of certain minerals may also affect the heart and nervous system. This can be prevented by giving extra fluids during treatment and by giving certain drugs, such as bicarbonate, allopurinol, and rasburicase, which help the body get rid of these substances.

Other drugs for acute myeloid leukemia

Acute promyelocytic leukemia (APL or AML M3) is different from other types of acute myeloid leukemia (AML) in some important ways. First, the leukemia cells (or blasts) contain proteins that when released into the bloodstream cause the blood to clot in an out-of -control way. This can lead to problems not only with blood clots, but also with severe bleeding. This was a big problem in the past, since treating APL with regular chemotherapy (chemo) drugs caused those cells to die and release these proteins into the bloodstream. Patients sometimes died from complications from the out of control clotting. Then experts realized that the leukemia cells in APL have a certain gene change that makes them sensitive to certain drugs that aren't like regular chemo drugs. These drugs signal the blasts to transform into mature (myeloid) cells. This process is known as differentiation and so these drugs are called differentiation agents. Since the blasts don't die, they don't release the harmful proteins into the blood, and so the clotting process doesn't get out of control. There are 2 drugs that are used for this in APL: all-trans-retinoic acid (ATRA, tretinoin, or Vesanoid®) and arsenic trioxide (ATO, Trisenox®).

ATRA: ATRA is a form of vitamin A that is often part of the initial treatment of APL. It is often given along with chemo - an anthracycline drug with or without cytarabine. For patients who can't take an anthracycline (often because of heart problems), ATRA can also be given with arsenic trioxide for the initial treatment of APL, in which case no regular chemo drugs are given. If ATRA is part of the initial treatment for APL, it is often used for some time after to keep the leukemia from coming back. For that part of the treatment, it may be used with chemo, with arsenic trioxide, or with both chemo and arsenic trioxide.

ATRA can have side effects similar to those seen if you take too much vitamin A. Symptoms include headache, fever, dry skin and mouth, skin rash, swollen feet, sores in the mouth or throat, itching and irritated eyes. It can also cause blood lipid levels (like those of cholesterol and triglycerides) to go up. Often blood liver tests become abnormal. These side effects often go away when the drug is stopped.

Arsenic trioxide: Arsenic trioxide (ATO) is a form of arsenic, which can be a poison. But doctors found that it can act in a way similar to ATRA in patients with APL. It can be given with ATRA, but it is also helpful in treating patients with APL whose leukemia came back after treatment with ATRA plus chemo. In those patients, ATO is given alone (without chemo).

Most side effects of arsenic trioxide are mild and can include fatigue (tiredness), nausea and vomiting, diarrhea, abdominal (belly) pain, and nerve damage (called neuropathy) leading to numbness and tingling in the hands and feet. Arsenic trioxide can also cause problems with heart rhythm, which can be serious. This is why your doctor may check your EKG often (even daily) while you are getting this drug.

Differentiation syndrome: The most important side effect of either of these drugs is a syndrome known as retinoic acid syndrome or differentiation syndrome. It is most often only seen during the first cycle of treatment. Symptoms include breathing problems due to fluid buildup in the lungs and around the heart, low blood pressure, kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the drugs for a while and giving a steroid such as dexamethasone.

Surgery for acute myeloid leukemia

Surgery has a very limited role in the treatment of acute myeloid leukemia. Because leukemia cells spread widely throughout the bone marrow and to many other organs, it is not possible to cure this type of cancer with surgery. Surgery rarely has any role even in the diagnosis, since a bone marrow aspirate and biopsy can usually diagnose leukemia. On rare occasions, an isolated tumor of leukemia cells (known as a granulocytic sarcoma or a chloroma) may be treated with surgery.

Often before chemotherapy is about to start, a small plastic tube, called a central venous catheter or venous access device (VAD), is inserted into a large vein. This may be done by a surgeon in the operating room, or by a special type of radiologist. The end of the tube is just under the skin or sticks out in the chest area or upper arm. The VAD is left in place during treatment to give intravenous (IV) drugs, such as chemotherapy, and to take blood samples. This lowers the number of needle sticks needed during treatment. It is very important for the patient to learn how to care for the VAD to prevent it from getting infected.

Radiation therapy for acute myeloid leukemia

Radiation therapy uses high-energy radiation to kill cancer cells. Radiation therapy is usually not part of the main treatment for people with acute myeloid leukemia (AML), but it is used in certain situations.

External beam radiation therapy, in which a machine delivers a beam of radiation to a specific part of the body, is the type of radiation used most often for AML. Before your treatment starts, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Radiation therapy is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time -- getting you into place for treatment -- usually takes longer.

There are a few instances in which radiation therapy may be used to help treat leukemia:

Radiation is sometimes used to treat leukemia that has spread to the brain and spinal fluid or to the testicles.

Radiation to the whole body is often an important part of treatment before a bone marrow or peripheral blood stem cell transplant .

It is used (rarely) to help shrink a tumor if it is pressing on the trachea (windpipe) and causing breathing problems. But chemotherapy is often used instead, as it may work more quickly.

Radiation can also be used to reduce pain in an area of bone that is invaded by leukemia, if chemotherapy hasn't helped.

The possible side effects of radiation therapy depend on where the radiation is aimed. Sunburn-like skin changes in the treated area are possible. Radiation to the abdomen can sometimes cause nausea, vomiting, or diarrhea. For radiation that includes large parts of the body, the effects may include fatigue and an increased risk of infection.

Bone marrow or peripheral blood stem cell transplant for acute myeloid leukemia

The usual doses of chemotherapy drugs can cause serious side effects to quickly dividing tissues such as the bone marrow. Even though higher doses of these drugs might be more effective, they are not given because they could severely damage the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

A stem cell transplant (SCT) allows doctors to use higher doses of chemotherapy and, sometimes, radiation therapy. After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.

Blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant, or PBSCT) or from the bone marrow (for a bone marrow transplant, or BMT). Bone marrow transplant was more common in the past, but it has largely been replaced by PBSCT.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. They differ with regard to the source of the blood-forming stem cells.

Allogeneic stem cell transplant : This is the most common form of SCT used to treat acute leukemia. In an allogeneic transplant, the stem cells come from someone else -- usually a donor whose tissue type is almost identical to the patient's. Tissue type is based on certain substances on the surface of cells in the body. These substances can cause the immune system to react against the cells. Therefore, the closer a tissue "match" is between the donor and the recipient, the better the chance the transplanted cells will "take" and begin making new blood cells.

The donor is most often a close relative, such as a brother or sister, since they are most likely to be a good match. If no close relatives match, a matched unrelated donor (MUD) may be an option in some cases. The stem cells from an unrelated donor come from volunteers whose tissue type has been stored in a central registry and matched with that of the patient. Sometimes umbilical cord stem cells are used. These stem cells come from blood drained from the umbilical cord and placenta after a baby is born and the umbilical cord is cut.

Using donor cells for SCT may be more effective than giving back the patient’s own cells (an autologous transplant) in part because of the "graft versus leukemia" effect. When the donor immune cells are infused into the body, they may recognize any remaining leukemia cells as being foreign to them and will attack them. This effect doesn't happen with autologous stem cell transplants

An allogeneic transplant is often the preferred type of transplant for acute myeloid leukemia (AML) when it is available, but its use is limited by the need for a matched donor. It is also limited by its side effects, which are too severe for most older people.

Non-myeloablative transplant (mini-transplant): Many older people can't tolerate a standard allogeneic transplant that uses high doses of chemotherapy. Some may be able to have a non-myeloablative transplant (also known as a mini-transplant or reduced-intensity transplant), where they receive lower doses of chemotherapy and radiation that do not completely destroy the cells in their bone marrow. They then receive the allogeneic (donor) stem cells. These cells enter the body and establish a new immune system, which sees the leukemia cells as foreign and attacks them (a "graft-versus-leukemia" effect).

Doctors have learned that if they use small doses of certain chemotherapy drugs and low doses of total body radiation, an allogeneic transplant can still sometimes work with much less toxicity. In fact, a patient can receive a non-myeloablative transplant as an outpatient. The major complication is graft-versus-host disease.

Many doctors still consider this procedure to be experimental in AML, and studies are under way to determine how useful it may be.

Autologous stem cell transplant: In an autologous transplant, a patient's own stem cells are removed from his or her bone marrow or peripheral blood. They are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation). A process called "purging" may be used to try to remove any leukemia cells in the samples. The stem cells are then reinfused into the patient's blood after treatment.

Autologous transplants are sometimes used for people with AML who are in remission after initial treatment and who don’t have a matched donor for an allogeneic transplant. Some doctors feel that it is better than standard "consolidation" chemotherapy  for these people, but not all doctors agree with this.

Autologous transplants are generally easier to tolerate than allogeneic transplants, but the high-dose chemotherapy can still cause major side effects. The patient is getting his or her own cells back, so the risk of some complications is smaller. This type of transplant can be done in any otherwise healthy person, although very old patients might not be suitable.

One problem with autologous transplants is that it is hard to separate normal stem cells from leukemia cells in the bone marrow or blood samples. Even after purging (treating the stem cells in the lab to try to kill or remove any remaining leukemia cells), there is the risk of returning some leukemia cells with the stem cell transplant.

The transplant procedure

Blood-forming stem cells from the bone marrow or peripheral blood are collected, frozen, and stored. The patient receives high-dose chemotherapy and sometimes also radiation treatment to the entire body. (Radiation shields are used to protect the lungs, heart, and kidneys from damage during radiation therapy.)

The treatments are meant to destroy any cancer cells in the body. They also kill the normal cells of the bone marrow and the immune system. After these treatments, the frozen stem cells are thawed and given as a blood transfusion. The stem cells settle into the patient's bone marrow over the next several days and start to grow and make new blood cells.

In an allogeneic SCT, the person getting the transplant may be given drugs to keep the new immune system in check. For the next few weeks the patient will get regular blood tests and supportive therapies as needed, which might include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition.

Usually within a couple of weeks after the stem cells have been infused, they begin making new white blood cells. This is followed by new platelet production and, several weeks later, new red blood cell production.

Patients usually stay in the hospital in protective isolation (guarding against exposure to germs) until their white blood cell count rises above 500. They may be able to leave the hospital when their white blood cell count is near 1,000. The patient is then seen in the outpatient clinic almost every day for several weeks. Because platelet counts take longer to return to a safe level, patients may get platelet transfusions as an outpatient.

Practical points: Bone marrow or peripheral blood SCT is a complex treatment. If the doctors think a patient may benefit from a transplant, it should be done at a hospital where the staff has experience with the procedure and with managing the recovery phase. Some bone marrow transplant programs may not have experience in certain types of transplants, especially transplants from unrelated donors.

SCT is very expensive (more than $100,000) and often requires a lengthy hospital stay. Because some types of SCT may be viewed as “experimental” by insurance companies, they may not pay for the procedure. It is important to find out what your insurer will cover before deciding on a transplant to get an idea of what you might have to pay.

Possible side effects: Side effects from SCT are generally divided into early and long-term effects.

The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy , and are due to damage to the bone marrow and other quickly dividing tissues of the body. They can include low blood cell counts (with fatigue and an increased risk of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss.

One of the most common and serious short-term effects is the increased risk for infection from bacteria, viruses, or fungi. Antibiotics are often given to try to prevent this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

Some complications and side effects can persist for a long time or may not occur until months or years after the transplant. These include:

Graft-versus-host disease (GVHD), which can occur in allogeneic (donor) transplants. This happens when the donor immune system cells attack tissues of the patient's skin, liver, and digestive tract. Symptoms can include weakness, fatigue, dry mouth, rashes, nausea, diarrhea, yellowing of the skin and eyes (jaundice), and muscle aches. In severe cases, GVHD can be life-threatening. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. Drugs that weaken the immune system are often given to try to keep GVHD under control.

Damage to the lungs, causing shortness of breath

Damage to the ovaries in women, causing infertility and loss of menstrual periods

Damage to the thyroid gland that causes problems with metabolism

Cataracts (damage to the lens of the eye that can affect vision)

Bone damage called aseptic necrosis (where the bone dies because of poor blood supply). If damage is severe, the patient will need to have part of the bone and the joint replaced.

Graft-versus-host disease is the most serious complication of allogeneic (donor) stem cell transplants. The most common symptoms are severe skin rashes and severe diarrhea. The liver and lungs may also be damaged. The patient may also become tired easily and have muscle aches. Sometimes the graft-versus-host disease becomes chronic and disabling and, if it is severe enough, can be life-threatening. Drugs that affect the immune system may be given to try to control it.

Complementary and alternative therapies for acute myeloid leukemia

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 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 to be helpful, and a few have even been found to be 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.

Typical treatment of acute myeloid leukemia (except promyelocytic M3)

Treatment of most cases of acute myeloid leukemia (AML) is usually divided into 2 chemotherapy (chemo) phases:

Remission induction (often just called induction)

Consolidation (post-remission therapy)

In some cases, people with AML may have very high numbers of leukemia cells in their blood when they are diagnosed, which can cause problems with normal circulation. Chemo may not lower the number of cells until a few days after the first dose. In the meantime, leukapheresis (sometimes just called pheresis) may be used before chemo. For this procedure, the patient's blood is passed through a special machine that removes white blood cells (including leukemia cells) and returns the rest of the blood cells and plasma to the patient. Two IV lines are required -- the blood is removed through one IV, and then is returned to the body through the other IV. Sometimes, a single large catheter is placed in the neck or under the collar bone for the pheresis -- instead of using IV lines in the arms. This type of catheter is called a central line and has both IVs built in. This treatment lowers blood counts right away. The effect is only for a short time, but it may help until the chemo has a chance to work.

Induction

This first part of treatment is aimed at getting rid of all visible leukemia. In younger patients, it usually involves treatment with 2 chemo drugs, cytarabine (ara-C) and an anthracycline drug such as daunorubicin (daunomycin) or idarubicin. Sometimes a third drug, 6-thioguanine, is added. This intensive therapy, which usually takes place in the hospital, typically lasts about a week.

How intense the treatment is may depend on a person's age and on other prognostic factors. Doctors often give more intensive chemo to people under the age of 60. Some older patients in good health may benefit from similar or slightly less intensive treatment.

People who are much older or are in poor health may not do well with intensive chemo. Treatment of these patients is discussed below in “Treating frail, older adults.”

Age, health, and other factors clearly need to be taken into account when considering treatment options. Doctors are also trying to determine whether people with certain gene or chromosome changes are more likely to benefit from more intensive treatment.

In rare cases where the leukemia has spread to the brain or spinal cord, chemo may be given into the cerebrospinal fluid (CSF) as well.

Induction destroys most of the normal bone marrow cells as well as the leukemia cells. During chemo and the next few weeks, the patient's blood cell counts will probably be dangerously low, and the patient may be very ill. Most patients need antibiotics and blood product transfusions. Drugs to raise white blood cell counts may also be used. Usually, the patient stays in the hospital during this time.

If induction is successful, no leukemia cells will be found in the blood, and the number of blast cells in the bone marrow will be less than 5% within a week or two. Normal bone marrow cells will return in a couple of weeks and start making new blood cells. The doctor will check a bone marrow biopsy to see if the leukemia is in remission. This is usually done at least 2 weeks after chemo ends.

If one week of treatment does not induce remission, the process may be repeated.

Induction is successful in up to 70% of all AML patients who get some type of intensive chemo. The actual chance of remission depends to a large part on a person's specific prognostic factors. For instance, older people are more likely to have unfavorable cytogenetic test results, are more likely to have a pre-existing blood disorder, and are less likely to be able to tolerate intensive therapy than younger patients, so generally their disease don't respond as well to treatment.

Remission induction usually does not destroy all the leukemia cells, and a small number often persist. Without more treatment, called consolidation, the leukemia is likely to return within several months.

Consolidation (post-remission therapy)

Induction is considered successful if remission is achieved. Further treatment is then given to try to destroy any remaining leukemia cells and help prevent a relapse. This is called consolidation.

For younger patients, the main options for AML consolidation therapy are:

Several cycles of high-dose cytarabine (ara-C) chemo (this is sometimes known as HiDAC)

Allogeneic (donor) stem cell transplant

Autologous stem cell transplant

Consolidation chemo differs from induction therapy in that usually only cytarabine is used. The drug is given at very high doses, typically over 5 days. This is repeated about every 4 weeks, usually for a total of 3 or 4 cycles.

Three years after this treatment, about 45% of patients younger than 60 years old will not show any signs of leukemia. But this number is affected by certain prognostic factors, such as whether the leukemia cells have certain gene or chromosome changes.

Another approach after successful induction therapy is a stem cell transplant. Patients first receive very high doses of chemo to destroy all bone marrow cells. This is followed by either an allogeneic (from a donor) or autologous (patient's own) stem cell transplant to restore blood cell production. Stem cell transplants have been found to reduce the risk of leukemia coming back more than standard chemo, but they are also more likely to have serious complications, including an increased risk of death from treatment.

Older patients or those in poor health may not be able to tolerate such intensive consolidation treatment. These patients may be treated with:

1 or 2 cycles of higher dose ara-C (usually not quite as high as in younger patients)

1 or 2 cycles of standard dose ara-C, possibly along with idarubicin or daunorubicin

Non-myeloablative stem cell transplant (mini-transplant)

Older patients generally don't do as well as those younger than 60. Unfortunately, studies have found that giving them more intensive therapy raises the risk of serious side effects (including treatment-related death) without providing much more of a benefit. In general, around 15% to 20% of older patients are still free of leukemia several years after treatment.

It is not always clear which of the treatment options is best for consolidation. They each have their pros and cons. Doctors look at several different factors when recommending what type of post-remission therapy a patient should receive. These include:

How many courses (cycles) of chemo it took to bring about a remission. If it took more than one course, some doctors recommend that the patient receive a more intensive program, which might involve a stem cell transplant.

The availability of a brother, sister, or an unrelated donor who matches the patient's tissue type. If a close enough tissue match is found, an allogeneic (donor) stem cell transplant may be an option, especially for younger patients.

The potential of collecting leukemia-free bone marrow cells from the patient. If lab tests show that a patient is in remission, collecting stem cells from the patient's bone marrow or blood for an autologous stem cell transplant may be an option. Stem cells collected from the patient would be purged (treated in the lab to try to remove or kill any remaining leukemia cells) to lower the chances of relapse.

The presence of one or more adverse prognostic factors, such as certain gene or chromosome changes, a very high initial white blood cell count, AML that develops from a previous blood disorder or after treatment for an earlier cancer, or spread to the central nervous system. These factors might lead doctors to recommend more aggressive therapy, such as a stem cell transplant. On the other hand, for people with good prognostic factors, such as favorable gene or chromosome changes, many doctors might advise holding off on a stem cell transplant unless the disease recurs.

The age of the patient. Older patients may not be able to tolerate some of the severe side effects that can occur with high-dose chemo or stem cell transplants.

The patient's wishes. There are many issues that revolve around quality of life that must be discussed. An important issue is the higher chance of early death from high-dose chemo or a stem cell transplant. This and other issues must be discussed between the patient and the doctor.

Stem cell transplants are intensive treatments with real risks of serious complications, including death, and their exact role in treating AML is not always clear. Some doctors feel that if the patient is healthy enough to withstand the procedure and a compatible donor is available, an allogeneic transplant offers the best chance for long-term survival. Others feel that studies have not yet shown this conclusively, and that in some cases a transplant should be reserved in case the leukemia comes back after standard treatment. Others feel that stem cell transplants should be given if the leukemia is likely to come back based on certain gene or chromosome changes. Research in this area continues to see which AML patients get the most benefit from stem cell transplant and what is the best transplant procedure.

Treatment of acute promyelocytic (M3) leukemia

Early diagnosis and treatment of acute promyelocytic leukemia (APL), the M3 subtype of acute myeloid leukemia (AML), is important because patients with APL may develop serious blood-clotting or bleeding problems. This used to be treated with blood-thinning medicines, but is less often a problem now that treatment includes drugs like all-trans-retinoic acid (ATRA). Other treatments might include transfusions of platelets or other blood products.

The treatment of most cases of APL differs from usual AML treatment. Initial treatment usually involves an anthracycline chemotherapy drug (daunorubicin or idarubicin) plus the non-chemotherapy drug, all-trans-retinoic acid (ATRA), which is a relative of vitamin A.

This treatment induces remission in about 80% to 90% of patients.

Patients who can't tolerate an anthracycline drug may get ATRA plus another drug called arsenic trioxide (Trisenox). The most serious possible side effect of this drug is a change in heart rhythm.

As with other subtypes of AML, patients with APL then receive post-remission treatment.

Consolidation therapy usually consists of 2 or more courses of chemotherapy (with an anthracycline), usually along with ATRA. Those who can't get an anthracycline usually get ATRA plus arsenic trioxide for several cycles.

Consolidation is often followed by maintenance therapy with ATRA for at least a year. Some doctors may also add low doses of chemotherapy, usually with the drugs 6-mercaptopurine (6-MP) and methotrexate.

The possible side effects from the chemotherapy part of this treatment are generally the same as those of standard AML induction chemotherapy. But both ATRA and arsenic can cause a problem called differentiation syndrome (it used to be called retinoic acid syndrome). Symptoms include breathing problems due to fluid buildup in the lungs, low blood pressure, kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the drug for a while and giving a steroid such as dexamethasone.

What if the leukemia doesn`t respond or comes back after treatment?

For most types of acute myeloid leukemia

If acute myeloid leukemia (AML) doesn't go away with the first treatment, newer drugs or more intensive doses of chemotherapy drugs may be tried, if they can be tolerated. A stem cell transplant may be tried in younger patients if a suitable stem cell donor can be found. Clinical trials of new treatment approaches may also be an option.

If the leukemia went away and has now come back, the treatment options may depend on the patient's age and health, and on how long the leukemia was in remission. AML most often recurs in the bone marrow and blood. The brain or cerebrospinal fluid (CSF) rarely will be the first place it recurs, but if it does, it is treated with chemotherapy given directly into the CSF.

For those whose remission lasted longer than 6 months, it is sometimes possible to put the leukemia into remission again with more chemotherapy, although this is not likely to be long-lasting. For younger patients (generally those younger than 60), most doctors would then advise a stem cell transplant if a suitable donor can be found. Clinical trials of new treatment approaches may also be considered.

If AML comes back sooner than 6 months, most doctors will advise a stem cell transplant for younger patients, if possible. Taking part in a clinical trial is another option.

If the leukemia keeps coming back or doesn't go away, further chemotherapy treatment will probably not be very helpful. If a stem cell transplant is not an option, a patient may want to consider taking part in a clinical trial of newer treatments.

For acute promyelocytic leukemia

For the 20% to 30% of patients with acute promyelocytic leukemia (APL) who don't respond to initial treatment or who relapse, arsenic trioxide (Trisenox) is often very effective. A stem cell transplant may be another option if a donor can be found.

If treatment with arsenic trioxide achieves a remission, further courses of this drug may be given. An autologous stem cell transplant may also be an option. If a second remission is not achieved, treatment options may include an allogeneic stem cell transplant or taking part in a clinical trial.

Palliative treatment

If a clinical trial is not an option, it is important at this time to focus on relieving the symptoms of the leukemia. This is known as palliative treatment. For example, the doctor may advise less intensive chemotherapy with the goal of slowing the leukemia growth instead of trying to cure it.

As the leukemia grows in the bone marrow it may cause pain. It is important that you be as comfortable as possible. Treatments that may be helpful include radiation and appropriate pain-relieving medicines. If medicines such as aspirin and ibuprofen don't help with the pain, stronger opioid medicines such as morphine are likely to be helpful.

Other common symptoms from leukemia are low blood counts and fatigue. Medicines or blood transfusions may be needed to help correct these problems. Nausea and loss of appetite can be treated with medicines and high-calorie food supplements. Infections that occur may be treated with antibiotics.

What will happen after treatment for acute myeloid leukemia?

Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about cancer coming back. (When cancer comes back after treatment, it is called recurrence.) This is a very common concern in people who have had cancer.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are living full lives. 

Follow-up care

Treatment for acute myeloid leukemia (AML) can continue for months or years. Even after treatment ends, you will need frequent follow-up exams -- likely every few months for several years. It is very important to keep all follow-up appointments. During these visits, your doctor will likely ask about symptoms, do physical exams, and order blood tests or bone marrow exams. Follow-up is needed to check for cancer recurrence, as well as possible side effects of certain treatments. Almost any cancer treatment can have side effects. Some may last for a few weeks to months, but others can last the rest of your life. This is the time for you to talk to your cancer care team about any changes or problems you notice and any questions or concerns you have.

If the leukemia comes back, it is usually while the patient is being treated or shortly after they have finished chemotherapy. If this happens, treatment would be as described in the section called "What if the leukemia doesn't respond or comes back after treatment?" It is unusual for AML to return if there are still no signs of the disease within a few years after treatment.

It is important to keep health insurance. Tests and doctor visits cost a lot, and even though no one wants to think of their cancer coming back, this could happen.

Lifestyle changes

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 choices to help you stay healthy and feel as well as you can. This can 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 start during cancer treatment.

Making healthier choices

For many people, a diagnosis of cancer helps them focus on their health in ways they may not have thought much about in the past. Are there things you could do that might make you healthier? Maybe you could try to eat better or get more exercise. Maybe you could cut down on the alcohol, or give up tobacco. Even things like keeping your stress level under control may help. Now is a good time to think about making changes that can have positive effects for the rest of your life. You will feel better and you will also be healthier.

You can start by working on those things that worry you most. 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 Society for information and support. This tobacco cessation and coaching service can help increase your chances of quitting for good.

Eating better

Eating right can be hard for anyone, but it can get even tougher during and after cancer treatment. Treatment may change your sense of taste. Nausea can be a problem. You may not feel like eating and lose weight when you don't want to. Or you may have gained weight that you can't seem to lose. All of these things can be very frustrating.

If treatment caused weight changes or eating or taste problems, do the best you can and keep in mind that these problems usually get better over time. You may find it helps to eat small portions every 2 to 3 hours until you feel better. You may also want to ask your cancer team about seeing a dietitian, an expert in nutrition who can give you ideas on how to deal with these treatment side effects.

One of the best things you can do after cancer treatment is put healthy eating habits into place. You may be surprised at the long-term benefits of some simple changes, like increasing the variety of healthy foods you eat. Getting to and staying at a healthy weight, eating a healthy diet, and limiting your alcohol intake may lower your risk for a number of types of cancer, as well as having many other health benefits.

Rest, fatigue, and exercise

Extreme tiredness, called fatigue, is very common in people treated for cancer. This is not a normal tiredness, but a "bone-weary" exhaustion that doesn't get better with rest. For some people, fatigue lasts a long time after treatment, and can make it hard for them to exercise and do other things they want to do. But exercise can help reduce fatigue. Studies have shown that patients who follow an exercise program tailored to their personal needs feel better physically and emotionally and can cope better, too.

If you were sick and not very active during treatment, it is normal for your fitness, endurance, and muscle strength to decline. Any plan for 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 twice a week. If you haven't exercised in a few years, you will have to start slowly – maybe just by taking short walks.

Talk with your health care team before starting anything. Get their opinion about your exercise plans. Then, try to find an exercise buddy so 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, you will need to balance activity with rest. It is OK to rest when you need to. Sometimes it's really hard for people to allow themselves to rest when they are used to working all day or taking care of a household, but this is not the time to push yourself too hard. Listen to your body and rest when you need to. 

Keep in mind exercise can improve your physical and emotional health.

It improves your cardiovascular (heart and circulation) fitness.

Along with a good diet, it will help you get to and stay at a healthy weight.

It makes your muscles stronger.

It reduces fatigue and helps you have more energy.

It can help lower anxiety and depression.

It can make you feel happier.

It helps you feel better about yourself.

And long term, we know that getting regular physical activity plays a role in helping to lower the risk of some cancers, as well as having other health benefits.

What`s new in acute myeloid leukemia research and treatment?

Researchers are now studying the causes, diagnosis, supportive care, and treatment of acute myeloid leukemia (AML) at many medical centers, university hospitals, and other institutions.

Genetics of leukemia

Scientists are making great progress in understanding how changes in a person's DNA can cause normal bone marrow cells to develop into leukemia cells. A greater understanding of the genes (regions of the DNA) involved in certain translocations or other chromosomal changes that often occur in AML is providing insight into why these cells become abnormal. Doctors are now learning how to use these changes to help them determine a person's outlook and whether they should receive more or less intensive treatment.

In the future, this information may also be used to help develop newer targeted therapies against AML (see below).

Gene expression profiling

This new lab technique is being studied to help identify and classify different cancers. Instead of looking at single genes, this test is able to look at the patterns of many different genes in the cancer cells at the same time. This may add to the information that comes from the currently used lab tests.

Detecting minimal residual disease

Progress in understanding DNA changes in AML has already provided a highly sensitive test for detecting the smallest amount of leukemia left after treatment (minimal residual disease), even when so few leukemia cells are present that they cannot be found by routine bone marrow tests.

The polymerase chain reaction (PCR) test can identify AML cells based on their gene translocations or rearrangements. This test can find one leukemia cell among a million normal cells. A PCR test can be useful in determining how completely the treatment has destroyed the AML cells.

Doctors are now trying to determine what effect minimal residual disease has on a patient's outlook, and how this might affect the need for further or more intensive treatment.

Improving chemotherapy

Studies are being done to find the most effective combination of chemotherapy (chemo) drugs while still avoiding unwanted side effects. This is especially important in older patients, who are less likely to benefit from current treatments.

Patients who have leukemia after a previous diagnosis of myelodysplastic syndrome (MDS) do not tend to do well with standard chemo. This is also true for patients who are weak from other medical problems on top of the leukemia. These patients may be treated with less intense chemo instead of standard induction and consolidation. This may consist of lower doses of cytarabine, drugs called demethylating agents, or the drug clofarabine (Clolar). Demethylating agents include the drugs decitabine (Dacogen®) and 5-azacytidine (Vidaza®). Laromustine, a type of chemo drug known as an alkylating agent, is also being tested as an option for in older adults with AML.

Tipifarnib, a newer type of drug known as a farnesyl transferase inhibitor, has also shown promise in early studies. Farnesyl transferase inhibitors are drugs that keep a protein that is very active in cancer from functioning. These drugs are now being tested in larger clinical trials.

The effectiveness of chemotherapy may be limited in some cases because the leukemia cells become resistant to it. Researchers are now looking at ways to prevent or reverse this resistance by using other drugs along with chemotherapy.

Stem cell transplants

Researchers continue to refine stem cell transplants to try to increase their effectiveness, reduce complications and determine which patients are likely to be helped by this treatment. Many studies are under way to try to help determine exactly when autologous, allogeneic, and mini-transplants might best be used.

Targeted therapies

New targeted drugs that specifically attack some of the genetic changes seen in AML are now being developed.

About 1 person out of 3 with AML has a mutation in the FLT3 gene. Several new drugs, called FLT3 inhibitors, target this gene. They have shown activity against AML in early studies, especially when combined with chemotherapy. So far, they are only available in clinical trials.

Other gene mutations, such as changes in the c-KIT gene, also appear to be important in some cases of AML, and may become important targets for new therapies. Drugs that target this gene, such as imatinib (Gleevec) and dasatinib (Sprycel) are already used against other types of leukemia, and are now being studied against AML.

Immunotherapy

Monoclonal antibodies are man-made versions of immune system proteins (antibodies) that are designed to attach to specific targets, such as substances on the surface of cancer cells. Some work by boosting the body's immune response against the cancer cells. Other monoclonal antibodies have radioactive chemicals or cell poisons attached to them. When they are injected into the patient, the antibodies act like a homing device, bringing the radioactivity or poison directly to the cancer cells, which kills them. Monoclonal antibodies are often used to treat lymphoma, but their use in leukemia has been more limited.

Gemtuzumab ozogamicin (Mylotarg) is a monoclonal antibody with a cell poison attached that was used in some older AML patients. Although it seemed promising in earlier studies, a more recent study found that it didn't help older patients more than chemo alone. For that reason, it has been taken off the market and is no longer available outside of a clinical trial.

Vaccine therapy: A recent study of an experimental vaccine had promising results. For this vaccine, white blood cells (cells of the immune system) are removed from the patient's blood and exposed to a protein found on many AML cells called Wilms' tumor 1 protein (WT1). These cells are then given back to the patient by infusion into a vein (IV). In the body, the cells induce other immune system cells to attack the patient's leukemia.

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