Acute Myeloid Leukemia (AML)

What is acute myeloid leukemia (AML)?

Acute myeloid leukemia (AML) is a rare cancer that affects your bone marrow and blood. It typically happens when certain genes or chromosomes mutate (change). AML usually affects people age 60 and older, but it can also affect younger adults and children. Acute myeloid leukemia is an aggressive cancer that can be life-threatening. Newer treatments are helping people to live longer with AML.

What are acute myeloid leukemia types?

There are several AML subtypes. They all affect your blood cell levels, but different types of AML cause different symptoms and respond to treatment in different ways.

Medical pathologists determine AML subtypes by examining cancerous cells under a microscope. They also look for changes in your chromosomes and mutations in certain genes that help manage how cells grow and function.

AML subtypes include:

• Myeloid leukemia: Cancer in cells that produce neutrophils, a white blood cell. Most people with AML have the myeloid leukemia subtype.
• Acute monocytic leukemia (AML-M5): Cancer in cells that produce monocytes, a white blood cell.
• Acute megakaryocytic leukemia (AMLK): Cancer in cells that produce red blood cells or platelets.
• Acute promyelocytic leukemia (APL): Cancer in promyelocytes (immature white blood cells) that keeps these cells from developing.

How common is acute myeloid leukemia?

Acute myeloid leukemia affects about 4 in 100,000 adults annually. Each year about 1,160 children receive an AML diagnosis.

What are acute myeloid leukemia symptoms?

Early on, AML symptoms may feel like you have a cold or flu that won’t go away. Acute myeloid leukemia is aggressive. That means you quickly develop new and more noticeable symptoms. Later symptoms include:

• Dizziness.
• Easy bruising or bleeding, including frequent nosebleeds and bleeding gums.
• Fatigue.
• Feeling cold.
• Fever.
• Night sweats.
• Frequent infections or infections that don’t go away.
• Headaches.
• Loss of appetite.
• Unexplained weight loss.
• Pale skin.
• Shortness of breath (dyspnea).
• Swollen lymph nodes.
• Weakness.
• Bone, back or abdominal pain.
• Tiny red spots on your skin (petechiae).
• Wounds or sores that don’t go away.

What causes acute myeloid leukemia?

Experts aren’t sure what causes acute myeloid leukemia. They do know the condition happens when certain genes or chromosomes mutate (change), creating abnormal blood cells. These genetic changes may happen:

• During your lifetime when something changes your DNA.
• If you inherited a genetic disorder that increases your risk of developing AML.
• If there was a change in certain genes in your biological parents’ sperm or egg.

How do genetic changes cause acute myeloid leukemia?

To understand how genetic changes cause AML, it may help to know more about your bone marrow and blood cells. Your bone marrow is soft, spongy tissue in the center of most of your bones. It makes:

• Stem cells (immature cells) that mature into red blood cells that carry oxygen.
• White blood cells that protect against infection.
• Platelets, which help your blood to clot.

Normally your bone marrow works like an efficient production line, consistently making the exact number of blood cells and platelets that your body needs to function. In AML, however, your bone marrow produces abnormal myeloid cells called myeloid blasts or myeloblasts.

Myeloid blasts don’t act like normal blood cells. Normal cells follow genetic directions that tell them when and how quickly they should multiply and grow. As cells get older, they die to make room in your bone marrow for new cells. Myeloid blasts don’t follow directions. They multiply uncontrollably and they don’t die. The continuous flow of myeloid blasts in your bone marrow means less room for healthy blood cells. Since there’s no room, your bone marrow stops making blood cells. Without new healthy blood cells, your body doesn’t have what it needs to function.

Moreover, as the myeloid blasts keep on multiplying, they begin to spill out of your bone marrow into your bloodstream. Once in your bloodstream, the myeloid cells travel to other parts of your body, including your central nervous system, brain and spinal cord.

What are the risk factors for acute myeloid leukemia?

While experts don’t know exactly what triggers the genetic mutations that cause AML, they do know about risk factors that increase your chance of developing the disease. (When you think about risk factors, it’s important to remember risk factors don’t mean you’ll get sick.) Acute myeloid leukemia risk factors include:

• Age. About half of all people with AML are 65 or older when they’re diagnosed. Again, AML typically affects adults but it can affect children.
• Smoking, including exposure to secondhand smoke.
• Cancer treatments, including chemotherapy and radiation therapy.
• Long-term exposure to chemical carcinogens such as benzene and formaldehyde.
• High-dose radiation exposure from a nuclear reactor accident or atomic bomb.
• Certain inherited (genetic) disorders.
• Other bone marrow disorders.

What genetic disorders increase the risk of developing AML?

Researchers know some inherited genetic mutations increase people’s risk for developing AML, including:

• Down syndrome.
• Ataxia telangiectasia.
• Li-Fraumeni syndrome.
• Klinefelter syndrome.
• Fanconi anemia.
• Wiskott-Aldrich syndrome, which affects platelet production.
• Bloom syndrome.
• Familial Platelet Disorder syndrome, which affects platelet disorder.

What bone marrow diseases increase the risk of developing AML?

Some people who have myeloproliferative neoplasms (myeloproliferative disorders) may develop acute myeloid leukemia. (Myelo means bone marrow. Proliferative means too many.) People with the following disorders may also develop ML:

• Polycythemia vera.
• Myelofibrosis.
• Thrombocytosis.
• Myelodysplastic syndrome.
• Aplastic anemia.

What are the complications of acute myeloid leukemia?

Early on, acute myeloid leukemia affects the number of healthy red and white blood cells and platelets that you have. If you don’t have enough healthy blood cells and platelets, you may develop the following conditions:

• Anemia.
• Thrombocytopenia.
• Pancytopenia (low blood cell and platelet levels).

How is acute myeloid leukemia diagnosed?

Healthcare providers use several tests to diagnose AML, including genetic tests to identify AML type. Providers typically start with a physical examination. They check for bruises, bleeding or infection. They check for enlarged (swollen) organs, specifically your liver, spleen and lymph nodes.

What tests diagnose acute myeloid leukemia?

You may have one or more of these tests:

• Complete blood count (CBC).
• Peripheral blood smear.
• Bone marrow biopsy.
• Spinal tap.

What genetic tests diagnose AML?

Medical pathologists do genetic tests to identify AML type. They may examine certain chromosomes or genes to see if they’ve mutated or changed. Knowing AML type helps providers decide which treatment is most likely to eliminate AML. Specific tests may include:

• Immunohistochemistry, which involves staining cells viewed under a microscope. The dye stains cells differently based on the cells’ chemicals.
• Flow cytometry.
• Karyotype test.
• Fluorescence-in-situ-hybridization (FISH), which detects chromosome changes.

What are treatments for acute myeloid leukemia?

Treatments may include chemotherapy, targeted therapy (including monoclonal antibody therapy) or allogeneic stem cell transplantation. Adults and children have the same treatment options. The goal is to put AML into complete remission. In AML, complete remission means tests show your blood counts are normal. It also means pathologists don’t see cancerous cells when they examine your bone marrow sample under a microscope.

Chemotherapy for AML

There are three phases to chemotherapy for AML — induction, consolidation and maintenance.

Remission induction therapy

This is the first step toward complete remission of AML. Treatment usually happens over several days. Some people need two rounds of induction therapy before AML is in complete remission. Providers may use the following chemotherapies in remission induction therapy:

• Cytarabine (Cytosar-U®).
• Daunorubicin (Cerubidine®).
• Idarubicin (Idamycin®).
• Azacitidine (Vidaza®).
• Decitabine (Dacogen®.
• Glasdegib (Daurismo®).
• Venetoclax (Venclexta®, Venclyxto®).

Experts estimate induction therapy results in remission for:

• More than 60% of children and teens.
• About 75% of adults age 60 and younger.
• About 50% of people over age 60.

Consolidation therapy

Consolidation therapy kills any remaining cancerous cells. It lowers the risk of cancer recurrence (coming back). Most people receive high-dose cytarabine (Ara-C) or HiDAC five days each month for three or four months.

Maintenance therapy

Often, consolidation therapy eliminates AML. In some cases, however, providers may recommend ongoing treatment using low doses of chemotherapy. Maintenance therapy may continue for months or years. Chemotherapy drugs for maintenance therapy may include:

• Azacitidine (Vidaza®).
• Decitabine (Dacogen®)
• Midostaurin (Rydapt®).

Targeted therapy

Like its name suggests, this treatment targets specific genetic mutations in cancerous cells. Targeting the mutations keeps cancerous cells from growing. Monoclonal antibody therapy is a form of targeted therapy. Providers may use targeted therapy to treat AML that’s come back or hasn’t responded to chemotherapy:

• Providers may use chemotherapy drugs midostaurin (Rydapt®) or gilteritinib (Xospata®) to treat people who have AML with a FTL3 gene mutation. About 25% to 30% of people with AML carry this mutation.
• They may use enasidenib (IDHIFA®) or ivosidenib (Tibsovo®) to treat people who have AML caused by mutation of their X gene.

Allogeneic stem cell transplantation

Allogeneic stem cell transplantation uses stem cells from related or unrelated donors. Providers may obtain stem cells from bone marrow, peripheral blood or cord blood (blood collected from umbilical cords after birth).

Treatment complications or side effects

All cancer treatments have side effects. In AML, stem cell transplantation has the most serious side effects. Chemotherapy may cause myelosuppression, when you don’t have the normal number of blood cells and platelets. Targeted therapy side effects vary based on the specific drugs used.

Understanding side effects is an important part of knowing how cancer treatment will affect your daily life. Your healthcare provider is your best resource of information about specific treatment side effects. Some people may benefit from palliative care to help manage side effects.

Can AML be prevented?

No, you can’t prevent acute myeloid leukemia. Experts know that genetic mutations cause acute myeloid leukemia but they don’t know what triggers them. They do know about risk factors that may cause AML. Risk factors you can modify include:

• Smoking, including exposure to second-hand smoke. If you smoke, try to quit. If you live or work around someone who smokes, try to limit how much time you spend with them when they’re smoking.
• Long-term exposure to certain carcinogenic chemicals, particularly benzene and formaldehyde. If you work around these carcinogens, be sure you follow all safety precautions, such as wearing protective clothing.

Can acute myeloid leukemia be cured?

Currently, allogeneic stem cell transplantation is the only way to cure acute myeloid leukemia. Depending on your situation, your provider may recommend stem cell transplantation as your first AML treatment or if you have AML that comes back within 12 months. Unfortunately, not everyone may be a candidate for stem cell transplantation.

What is the prognosis for AML?

There are two sides of the coin in acute myeloid leukemia prognoses. One side is complete remission. The other is recurrence, when AML comes back:

• Overall, an estimated 50% to 80% of people with acute myeloid leukemia achieve complete remission after treatment. Complete remission happens more often in children and people under age 60. Remission may last for months or years.
• About 50% of people who achieve complete remission develop recurrent AML. When that happens, providers may recommend additional chemotherapy or stem cell transplantation. They may suggest participation in a clinical trial.

If you or your child has AML, ask your provider to explain what you can expect.

What is the survival rate of acute myeloid leukemia?

Acute myeloid leukemia is a complicated illness. There are several AML subtypes, which makes it difficult to be specific about survival rates.

For example, the five-year survival rate for children under age 15 is 67%. But some research suggests that five-year survival rate increases to more than 80% in children who have the APL subtype. And age makes a difference. In general, 30% of adults with acute myeloid leukemia are alive five years after diagnosis. Remember, AML typically affects people age 60 and older who may have other health issues.

It’s important to remember that survival rates reflect the experiences of large groups of people with AML. In this case, survival rate data includes survival rates from 2012 to 2018, and there are some new and more effective treatments for AML.

Many things affect how long you’ll live with acute myeloid leukemia. That means your healthcare providers, the people who know your medical history and your overall health, are your best resources for information.

How do I take care of myself?

It’s not easy to live with cancer that may come back. Getting involved with cancer survivorship programs is one way to take care of yourself. You may not be able to keep acute myeloid leukemia from coming back. But you can take steps to be as healthy as possible, no matter what. Here are some suggestions:

• Treatments for acute myeloid leukemia may affect your diet. You need to eat well to stay strong. If you’re having trouble eating, ask to speak to a nutritionist.
• AML treatment side effects can be hard to manage. If you need to, talk to your provider about palliative care.
• Cancer is stressful. You may be able to manage stress with exercise. But check with your provider before starting a new or aggressive exercise program.
• Cancer can be lonely. AML is a rare disease. You may feel anxious about discussing your situation. In that case, consider joining a support group.
• Acute myeloid leukemia can be exhausting. Treatment may sap your energy. Try to remember to get as much sleep as you need.

When should I see my healthcare provider?

You’ll probably see your healthcare provider through remission, particularly if you’re receiving maintenance therapy. Your provider will discuss what kinds of symptoms may be signs AML is coming back so you know when to contact them for new or additional treatment.

What questions should I ask my healthcare provider?

If you have AML, you may want to ask the following questions:

• What type of AML do I have?
• What are my treatment options?
• What are the treatment risks and side effects?
• How can I manage treatment side effects?
• What type of follow-up care do I need after treatment?
• Should I look out for signs of complications?
• Are there clinical trials I should consider?

A note from Cleveland Clinic

Acute myeloid leukemia (AML) is a rare cancer that affects your bone marrow and blood. AML typically affects people age 65 and older, but it can affect children and teenagers. Thanks to newer treatments, more people are living with AML that’s in remission after treatment. And while the cancer can come back, medical researchers are investigating ways to treat recurrent AML.

If you or your child has acute myeloid leukemia, you may feel as if you’ve stepped from solid ground into a sea of uncertainty. You may wonder if treatment will lead to remission. If it does, you may worry how long remission will last. Your healthcare providers understand how you feel. They’ll be with you as you navigate AML’s challenges.