Acute myeloid leukemia (AML): Full guide

What is AML?

Acute myeloid leukemia (AML) is a cancer of the blood-forming cells in the bone marrow. Bone marrow is the soft, spongy tissue inside your bones where blood cells are made.

Your marrow normally makes three kinds of blood cells. White blood cells fight infection. Red blood cells carry oxygen. Platelets help your blood clot. In AML, young cells called blasts grow out of control and do not mature. They crowd out healthy cells, so counts of normal blood cells drop.

"Acute" means it grows fast, over days to weeks. That is why treatment usually starts soon after diagnosis. "Myeloid" means it starts in the cells that would normally become red cells, platelets, or certain white cells.

AML is the most common acute leukemia in adults. Most people are in their late 60s or older when it is found. Some cases follow earlier chemotherapy or radiation, or an earlier blood disorder such as MDS. Most of the time, there is no clear cause.

Common signs are tiredness, shortness of breath, fevers or infections, easy bruising, nosebleeds, or bleeding gums. Some people are cured, especially with a stem cell transplant. Your care team will explain the goal of your treatment.

Types

AML with gene changes that define it

Many types of AML are now named for a key gene or chromosome change, such as NPM1, or a swap between chromosomes 8 and 21. The name tells your care team a lot about how the leukemia may act and which drugs may help.

Acute promyelocytic leukemia (APL)

A special type of AML caused by a swap between chromosomes 15 and 17. It can cause serious bleeding or clotting at the start, so it is a medical emergency. The good news is that it is one of the most curable leukemias. It is treated with a vitamin A-like pill called ATRA and a medicine called arsenic trioxide, often without regular chemotherapy.

Core binding factor AML

AML with certain chromosome changes, called t(8;21) or inv(16). It usually responds well to chemotherapy. An antibody drug called gemtuzumab ozogamicin is often added.

AML related to MDS or earlier blood problems

AML that grows out of a slower marrow disease, such as myelodysplastic syndrome (MDS). It can be harder to treat. A special form of chemotherapy called CPX-351 (Vyxeos) is sometimes used.

Therapy-related AML

AML that develops after chemotherapy or radiation for another illness, often years later. It is usually treated like higher-risk AML.

AML with TP53 changes

AML with a change in the TP53 gene. It is harder to treat and more likely to come back. A clinical trial is often a good choice.

Myeloid sarcoma

A rare form where AML cells form a lump outside the marrow, such as in the skin or gums. It is treated like AML in the marrow.

Tests you may have

Complete blood count (CBC) and blood smear

A CBC counts your white cells, red cells, and platelets. A smear lets a specialist look at your blood under a microscope. Blasts in the blood are often the first clue.

Bone marrow biopsy and aspirate

A needle takes liquid marrow and a small piece of bone, usually from the back of the hip. You get numbing medicine first. It confirms the diagnosis and gives cells for gene tests.

Flow cytometry

A lab test that looks at markers on the surface of the cells. It confirms that the leukemia is myeloid and not lymphoid. It can also be used later to look for tiny amounts of leukemia.

Chromosome and gene tests

Tests called karyotype, FISH, PCR, and next-generation sequencing look for changes in the leukemia cells. Some results, such as FLT3, come back within days and can change your first treatment.

Clotting tests

These check how well your blood clots. They are very important in APL, where clotting problems can be dangerous.

Heart test (echocardiogram)

An ultrasound of your heart. Some chemotherapy drugs can strain the heart, so your team checks it before starting.

HLA typing

A blood or cheek swab test to find a stem cell donor match. It is often done early, in case a transplant is needed later. Brothers and sisters may be tested too.

Lumbar puncture (spinal tap)

A thin needle takes fluid from your lower back. It is not needed for most people with AML. It may be done if there are signs that leukemia has reached the brain or spinal fluid.

Risk groups and phases

AML does not have stages like many other cancers. That is because it is already in the blood and marrow throughout the body. AML is usually diagnosed when blasts make up 20 out of every 100 cells in the marrow or blood. With some gene changes, it can be diagnosed with fewer blasts.

Instead of stages, doctors use risk groups. These are based mostly on the gene and chromosome changes in your leukemia cells. A common system comes from a group of experts called the European LeukemiaNet (ELN). Risk groups help predict how AML will respond and whether a stem cell transplant is a good idea.

Treatment also happens in phases. Knowing which phase you are in helps you understand what comes next.

Favorable risk

AML with changes that usually respond well, such as NPM1 without a FLT3-ITD change, core binding factor AML, or certain CEBPA changes. Many people do not need a transplant in first remission.

Intermediate risk

AML that fits neither the favorable nor the adverse group. A transplant is often discussed, depending on your health and test results.

Adverse risk

AML with changes that are harder to treat, such as TP53 changes or complex chromosome changes. A transplant is often advised if you are well enough.

Induction

The first phase. The goal is to clear the leukemia from the marrow and reach remission.

Consolidation

Treatment after remission to kill leukemia cells that are left. This may be more chemotherapy or a stem cell transplant.

Maintenance

Lower-intensity treatment, often pills, given for a longer time to help keep AML from coming back.

Remission

Complete remission means the marrow looks normal, blasts are under 5 out of 100 cells, and blood counts have recovered. It does not always mean cure, so treatment usually continues.

Measurable residual disease (MRD)

Very sensitive tests can find tiny amounts of leukemia that a microscope cannot see. Being MRD-negative is a good sign. MRD results can help decide about transplant.

Gene and lab tests to know

AML cells have gene changes that healthy cells do not. Testing for these is a key part of diagnosis. Some results point to a targeted drug made for that exact change.

Ask that your leukemia be tested for FLT3, NPM1, and IDH1 and IDH2 at diagnosis. FLT3 results usually come back within a few days. If it is safe, your team may wait for some results before choosing your treatment.

FLT3 (ITD or TKD)

One of the most common changes in AML. It can make AML grow faster. Pills called FLT3 inhibitors help. Midostaurin or quizartinib is added to chemotherapy at diagnosis. Gilteritinib is used if AML comes back, and sometimes after transplant.

NPM1

A common change that often means a better response to treatment, especially without FLT3-ITD. It can also be tracked with a very sensitive blood or marrow test to look for MRD. Newer pills called menin inhibitors can help if AML with NPM1 comes back.

IDH1 and IDH2

Changes found in about 1 in 5 people with AML. Pills target them: ivosidenib or olutasidenib for IDH1, and enasidenib for IDH2. Ivosidenib can be combined with azacitidine as a first treatment.

TP53

A change linked to AML that is harder to treat. It affects which treatment and clinical trials make sense.

KMT2A rearrangement

A chromosome change linked to higher-risk AML. Menin inhibitors, such as revumenib, can treat AML with this change when it comes back.

CEBPA

A change that, in certain forms, is linked to a better response to chemotherapy.

PML-RARA

The gene change that defines APL. Finding it means you need ATRA and arsenic trioxide right away.

CD33

A protein on the surface of many AML cells. The antibody drug gemtuzumab ozogamicin targets it.

Main treatments

Intensive induction chemotherapy ("7+3")

For people who are fit enough, the classic first treatment is cytarabine for 7 days plus daunorubicin or idarubicin for 3 days. It is given in the hospital, and you usually stay about 4 weeks while your counts recover. A FLT3 pill or gemtuzumab ozogamicin may be added based on your gene results.

Consolidation

After remission, most people get more rounds of chemotherapy, often high-dose cytarabine. Others move on to a stem cell transplant.

Azacitidine plus venetoclax

For people who are older or have health problems that make intensive chemotherapy unsafe, this is a standard first treatment. Azacitidine is a shot or IV given for several days each month. Venetoclax is a daily pill. Decitabine can be used in place of azacitidine. It can often be given mostly as an outpatient, though the first cycle may start in the hospital.

Other lower-intensity choices

Ivosidenib with azacitidine is an option for AML with an IDH1 change. Low-dose cytarabine with venetoclax is another choice. Doses and schedules are often adjusted to help blood counts recover.

Targeted pills

FLT3 inhibitors (midostaurin, quizartinib, gilteritinib), IDH inhibitors (ivosidenib, olutasidenib, enasidenib), and menin inhibitors (revumenib, ziftomenib) are used at different points, depending on your gene changes.

Maintenance

Some people who reach remission take a pill afterward to help keep AML away. Oral azacitidine (Onureg) is one option for people who are not going to transplant. A FLT3 inhibitor may be continued for AML with a FLT3 change.

Allogeneic stem cell transplant

You get strong treatment, then stem cells from a donor. The donor's immune cells can attack leukemia cells left behind. It offers the best chance of cure for many people with intermediate or adverse risk AML. It has serious risks, so your team will weigh it carefully. Reduced-intensity transplants allow more older adults to have one.

Treatment for APL

ATRA pills plus arsenic trioxide IV. For higher-risk APL, a chemotherapy drug is added. Treatment starts as soon as APL is suspected, even before the gene test is back, because early bleeding is the main danger.

Relapsed or refractory AML

If AML comes back or does not respond, options include targeted pills, other chemotherapy, a transplant, or a clinical trial. Your gene changes are often tested again, because they can change over time.

Supportive and comfort-focused care

Transfusions, antibiotics, and other care to treat symptoms are part of every plan. Some people choose care focused on comfort. Palliative care teams can help at any point, alongside leukemia treatment.

Infection, transfusion, and other side effects

Infections and fever

AML and its treatment cause very low white cell counts, called neutropenia. A fever can be a sign of a serious infection and needs care right away. You may take pills to prevent bacterial, fungal, and viral infections.

Blood and platelet transfusions

Most people need red cell and platelet transfusions during treatment. They help with tiredness and lower the risk of bleeding.

Bleeding and bruising

Low platelets can cause nosebleeds, bleeding gums, tiny red spots on the skin, or easy bruising. Use a soft toothbrush and an electric razor. Avoid aspirin and ibuprofen unless your team says they are okay.

Tumor lysis syndrome

When many leukemia cells die quickly, they release salts that can harm the kidneys and heart. It is most likely at the start of treatment, including venetoclax. Your team gives fluids and medicine and checks your blood closely.

Nausea, mouth sores, and hair loss

Chemotherapy can cause nausea, mouth sores, diarrhea, and hair loss. Anti-nausea medicine and gentle mouth care help. Hair usually grows back.

Differentiation syndrome

With ATRA, arsenic, IDH inhibitors, and menin inhibitors, leukemia cells can mature quickly and cause fever, trouble breathing, swelling, weight gain, or kidney problems. It is treatable with steroids if caught early. Call right away if you notice these signs.

Heart rhythm changes

Some drugs, such as arsenic trioxide, quizartinib, gilteritinib, and menin inhibitors, can affect the heart's electrical rhythm. Your team checks EKGs and your blood salts. Tell them about all other medicines you take.

Low counts from venetoclax

Venetoclax works well but can keep counts low for a long time. Your team may shorten the number of days you take it each month. Some antifungal medicines raise venetoclax levels, so doses may be adjusted.

Fatigue

Tiredness is very common. Short walks, rest breaks, and help from family and friends can make a difference.

Graft-versus-host disease (GVHD)

After a donor transplant, donor immune cells can attack your skin, gut, liver, or other organs. Signs include rash, diarrhea, and yellow skin or eyes. It can be treated, and you will take medicines to prevent it.

Living with and after AML

The first weeks of AML treatment are often the hardest. You may spend a lot of time in the hospital or at the clinic for blood counts and transfusions. It helps to have a caregiver, and to ask for help with rides, meals, and child care.

After treatment, you will have regular blood tests and sometimes bone marrow tests. These check that the leukemia has not come back. Most relapses happen in the first 2 to 3 years. Tell your care team about fevers, new bruises, or feeling more tired.

After a donor stem cell transplant, recovery can take months to a year or more. You will need to get your childhood vaccines again. You will also be watched for GVHD and long-term effects on the heart, lungs, bones, hormones, and eyes.

Treatment can affect fertility. If you may want children, ask about saving sperm or eggs, if time allows. Because AML often needs quick treatment, this talk should happen right away.

It is normal to feel shocked, scared, or overwhelmed. Caregivers often carry a heavy load too. Social workers, counselors, palliative care teams, and support groups can help. Blood Cancer United (formerly the Leukemia and Lymphoma Society) offers free support and information.