Typical Treatment of Acute Myeloid Leukemia (Except APL)

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

• Remission induction (often just called induction)
• Consolidation (post-remission therapy)

A third phase, known as maintenance, is sometimes used after consolidation.

Chemotherapy (chemo) is the main treatment for most types of AML, although other treatments might be used as well.

The acute promyelocytic leukemia (APL) subtype of AML is treated differently.

Treatment for AML often needs to start as quickly as possible after it is diagnosed because it can progress very quickly. Sometimes another type of treatment needs to be started even before the chemo has had a chance to work.

Treating leukostasis

Some people with AML have very high numbers of leukemia cells in their blood when they are first diagnosed, which can cause problems with normal blood circulation. This is called leukostasis, and it needs to be treated right away. 

If induction chemotherapy (see below) can't be started right away for some reason, sometimes a chemo drug such as hydroxyurea or cytarabine can be given to lower the number of leukemia cells quickly.

Another option might be to use leukapheresis (sometimes just called pheresis) before starting chemo. In this treatment, the person’s blood is passed through a special machine that removes white blood cells (including leukemia cells) and returns the rest of the blood to the person.

Two intravenous (IV) lines are required – the blood is removed through one IV, goes through the machine, and then is returned to the person through the other IV. Sometimes, a single large catheter is placed in a vein in the neck or under the collar bone for the pheresis, instead of using IV lines in both arms. This type of catheter is called a central venous catheter (CVC) or central line and has both IVs built in.

This treatment lowers the number of leukemia cells right away. The effect is only for a short time, but it may help until the chemo has a chance to work.

Induction

The first phase of treatment for AML is aimed at quickly getting rid of as many leukemia cells as possible.

How intense the treatment can be depends to some extent on a person’s age and overall health. Doctors often give the most intensive chemo to people who are younger, but some older people in good health may benefit from similar or slightly less intensive treatment. People who are much older or are in poor health might not do well with intensive chemo. Treatment for these people is discussed below.

Other factors also need to be taken into account when considering treatment options. For example, some subtypes of AML tend to have a better or worse prognosis (outlook), which can affect how intense treatment should be. And people whose leukemia cells have certain gene or chromosome changes are more likely to benefit from certain types of treatment.

In younger people, induction often includes treatment with 2 chemo drugs:

• Cytarabine (ara-C)
• An anthracycline drug such as daunorubicin (daunomycin) or idarubicin

This is often called a 7 + 3 regimen, because it means getting cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days.

In some situations, a third drug might be added as well to try to improve the chances of putting the leukemia into remission:

• For people whose leukemia cells have an FLT3 gene mutation, a targeted therapy drug such as midostaurin (Rydapt) or quizartinib (Vanflyta) might be given along with chemo.
• For people whose leukemia cells have the CD33 protein, the targeted drug gemtuzumab ozogamicin (Mylotarg) might be added to chemo.

People with poor heart function might not be able to be treated with anthracyclines, so they may be treated with another chemo drug instead, such as fludarabine or cladribine.

In rare cases where leukemia has spread to the brain or spinal cord, chemo may also be given into the cerebrospinal fluid (CSF). This is known as intrathecal chemo. Radiation therapy might be used as well.

People typically need to stay in the hospital during induction (and possibly for some time afterward). Induction destroys most of the normal bone marrow cells as well as the leukemia cells, so most people develop dangerously low blood counts, and may be very ill. Most people need antibiotics and blood product transfusions. Drugs to raise white blood cell counts (called growth factors) may also be used. Blood counts tend to stay low for a few weeks.

About a week or two after chemo is done, the doctor will do a bone marrow aspiration and biopsy to see how well treatment is working. This should show few bone marrow cells (hypocellular bone marrow) and only a small portion of blasts (making up no more than 5% of the bone marrow) for the leukemia to be considered in remission.

Most people with leukemia go into remission after the first round of chemo. But if the biopsy shows that there are still leukemia cells in the bone marrow, another round of chemo may be given, either with the same drugs or with another regimen.

This second round of chemo is known as reinduction. Sometimes a stem cell transplant is recommended at this point. If it isn’t clear on the bone marrow biopsy whether the leukemia is still there, another bone marrow biopsy may be done again in about a week.

Over the next few weeks, normal bone marrow cells should return and start making new blood cells. The doctor may do other bone marrow biopsies during this time. When the blood cell counts recover, the doctor will again check cells in a bone marrow sample to see if the leukemia is in remission.

Remission induction usually does not destroy all the leukemia cells, and a small number often remain. Without post-remission therapy (consolidation), the leukemia is likely to return within several months.

Consolidation (post-remission therapy)

Induction is considered successful if the leukemia goes into remission. Further treatment (called consolidation) is given then to try to destroy any remaining leukemia cells and help prevent a relapse.

Consolidation for younger people

For younger people (typically those under 60), the main options for consolidation therapy are:

• Several cycles of chemo with high-dose cytarabine (ara-C) (sometimes known as HiDAC)
• Allogeneic (donor) stem cell transplant
• Autologous stem cell transplant

Other chemo regimens might be options as well. The best option for each person depends on the risk of the leukemia coming back after treatment, as well as other factors.

For HiDAC, cytarabine 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. Again, each round of treatment is typically given in the hospital because of the risk of serious side effects.

For people who got a targeted drug such as midostaurin (Rydapt) or quizartinib (Vanflyta) along with chemo during induction, this is typically continued during consolidation.

For people who got chemo plus the targeted drug gemtuzumab ozogamicin (Mylotarg) for induction therapy, a similar regimen might be used for consolidation.

Another approach after induction therapy is to give high doses of chemo followed by either an allogeneic (from a donor) or autologous (patient’s own) stem cell transplant. 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 dying from treatment.

Consolidation for people who didn't get intensive induction

As with induction, some older people or those in poor health may not be able to tolerate intensive consolidation treatment. Often, giving them more intensive therapy raises the risk of serious side effects (including dying from treatment) without providing much more of a benefit. These people may be treated with regimens such as:

• Higher-dose cytarabine (usually not quite as high as in younger people)
• Standard-dose cytarabine, possibly along with idarubicin, daunorubicin, or mitoxantrone. (For people who got a targeted drug such as midostaurin or quizartinib during induction, this is typically continued during consolidation as well.)
• A non-myeloablative stem cell transplant (mini-transplant)

Factors affecting choice of consolidation treatment

It's not always clear which treatment option is best for consolidation. Each can have pros and cons. Doctors look at several factors when recommending what type of treatment a person should get. These include:

• How many courses (cycles) of chemo it took to bring about a remission. If it took more than one, some doctors recommend that the person get a more intensive program, which might include 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 people.
• The possibility of collecting leukemia-free bone marrow cells from the patient. If lab tests show that a person is in remission, collecting stem cells from the person’s bone marrow or blood for an autologous stem cell transplant may be an option. Stem cells collected from the person 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 of AML 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 person’s age and overall health. Older people or those with other health problems might not be able to tolerate some of the severe side effects that can occur with high-dose chemo or stem cell transplants.
• The person’s wishes. There are many issues relating to quality of life that need to be considered. For example, an important issue is the higher chance of having serious or even life-threatening side effects 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 risks of serious complications, including dying, and their exact role in treating AML isn't always clear. Many doctors feel that if a person is healthy enough to withstand an allogeneic transplant and a compatible donor is available, this option offers the best chance for long-term survival. Others feel that in some cases it might be better to hold off on doing a transplant in case the leukemia comes back after standard treatment. Doctors continue to study which people with AML will get the most benefit from stem cell transplant and which type of transplant is best in each situation.

Maintenance (post-consolidation) therapy

In some situations, maintenance therapy might be an option for further treatment. This is also sometimes called post-consolidation therapy. In this phase, treatment is given over a longer period of time (and often at lower doses). The intent is to keep the leukemia from coming back for as long as possible.

Not everyone with AML needs maintenance therapy. But it might be an option for some people if there’s a higher risk of the leukemia coming back, or if a person can’t get (or can’t complete) intense initial treatment for some reason.

For some people whose AML goes into remission after induction (or even after consolidation), maintenance treatment with the oral chemo drug azacitidine (Onureg) or a similar drug might be an option.

For people who received a targeted drug as part of their initial treatment, continuing the targeted drug (without chemo) might be an option.

Treating people who are frail, older, or who don't want intensive treatment

Treatment of AML in younger people who are otherwise in good health and are willing to get intensive treatment is fairly standard. It includes cycles of intensive chemo, sometimes along with a targeted drug or a stem cell transplant (as discussed above). Many people who are older are healthy enough to be treated in the same way, although sometimes the chemo may be less intense.

But people who are much older or are in poor health might not be able to tolerate this intense treatment. In fact, intense chemo could actually shorten their lives. And some people might decide they don't want such intense treatment, even if they could get it, because of the serious side effects it might cause. Treatment of these people is often not divided into phases, but it may be given every so often for as long as it seems helpful.

Options for these people might include:

• Low-intensity chemo with a drug such as low-dose cytarabine (LDAC), azacitidine (Vidaza), or decitabine (Dacogen) 
• Low-intensity chemo plus a targeted drug such as venetoclax (Venclexta) or glasdegib (Daurismo) 
• A targeted drug, such as: 
  • Gemtuzumab ozogamicin (Mylotarg), if the AML cells have the CD33 protein
  • Ivosidenib (Tibsovo), alone or with the chemo drug azacitidine, if the AML cells have an IDH1 gene mutation
  • Enasidenib (Idhifa), if the AML cells have an IDH2 gene mutation

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