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.

Treating frail, older adults

Treatment of AML in people under 60 is fairly standard. It involves cycles of intensive chemo (discussed above). Many patients older than 60 are healthy enough to be treated in the same way, although sometimes the chemo may be less intense. People who are much older or are in poor health may not be able to tolerate this intense treatment. In fact, intense chemo could actually shorten their lives.

In some cases, doctors may recommend low-intensity chemo with a low dose of cytarabine given in cycles. In some cases, this may induce remission. In others, it may control the leukemia for a time. Treatment of these patients is often not divided into induction and consolidation, but may be given every so often as long as it seems helpful.

Sometimes, these patients may be treated with drugs used to treat myelodysplastic syndrome, like 5-azacytidine or decitabine. These drugs are not approved to treat AML, but still may be helpful. Our document Myelodysplastic Syndromes has more information about these drugs.

Some patients decide against chemo and other drugs and instead choose supportive care. This focuses on treating any symptoms or complications that arise and keeping the person as comfortable as possible.