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 usually 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. Chemo can take a few days to lower the number of leukemia cells in the blood. In the meantime, leukapheresis (sometimes just called pheresis) might be used before chemo.

In leukapheresis, 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 to the patient. Two intravenous (IV) lines are required – the blood is removed through one IV, goes through the machine, and then is returned to the patient 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 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 phase of treatment is aimed at quickly getting rid of as many leukemia cells as possible. How intense the treatment is can depend on a person’s age and health. Doctors often give the most intensive chemo to people under the age of 60, but 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 might not do well with intensive chemo. Treatment for these patients is discussed below.

Other factors also need to be taken into account when considering treatment options. For example, people whose leukemia cells have certain gene or chromosome changes are more likely to benefit from certain types of treatment.

In younger patients, such as those under 60, induction often involves treatment with 2 chemo drugs:

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

This is sometimes called a 7 + 3 regimen, because it consists of 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 remission:

• For patients whose leukemia cells have an FLT3 gene mutation, the targeted therapy drug midostaurin (Rydapt) might be given along with chemo.
• For patients whose leukemia cells have the CD33 protein, the targeted drug gemtuzumab ozogamicin (Mylotarg) might be added to chemo.
• Adding the chemo drug cladribine might be another option for some people.

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

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

Patients 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 patients develop dangerously low blood counts, and may be very ill. Most patients 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 after chemo is done, the doctor will do a bone marrow biopsy. It 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. 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 will 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 remission is achieved. Further treatment (called consolidation) is then given to try to destroy any remaining leukemia cells and help prevent a relapse.

Consolidation for younger patients

For younger patients (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

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.

For people who got the targeted drug midostaurin (Rydapt) during induction, this is typically continued during consolidation. Again, each round of treatment is typically given in the hospital because of the risk of serious side effects.

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

Another approach after induction therapy is to give very 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 death from treatment.

Consolidation for patients who are older or have other health problems

Older patients 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 treatment-related death) without providing much more of a benefit. These patients may be treated with:

• Higher-dose cytarabine (usually not quite as high as in younger patients)
• Standard-dose cytarabine, possibly along with idarubicin, daunorubicin, or mitoxantrone (For people who got the targeted drug midostaurin (Rydapt) during induction, this is typically continued during consolidation as well.)
• 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 has 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 patient 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 patients.
• The possibility 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 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 patient’s age and overall health. Older patients 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 patient’s wishes. There are many issues relating to quality of life that need to be considered. An important issue is the higher chance of 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 an allogeneic transplant and a compatible donor is available, this option 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. Still 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 study which AML patients get the most benefit from stem cell transplant and which type of transplant is best in each situation.

Maintenance

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) 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 frail or older adults

Treatment of AML in people under 60 is fairly standard. It involves cycles of intensive chemo, sometimes along with a stem cell transplant (as discussed above). Many people 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. Treatment of these people is often not divided into phases, but it may be given every so often as long as it seems helpful.

Options for people who are older or are in poor health 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 care. This focuses on treating any symptoms or complications that arise and keeping the person as comfortable as possible.