Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a type of cancer that starts initially in the bone marrow where blood cells are produced and then moves quickly to the blood cells themselves. From there, the cancer can spread to other parts of the body including the liver, spleen, skin, brain, and spinal cord.

In the United States, nearly 20,000 cases of AML are diagnosed annually, most of them in adults. Around 12,000 people die of AML each year.

Unlike other forms of leukemia, which tend to strike the young, AML typically affects adults over 65. Among this age group, the five-year survival rate is relatively poor, hovering at around 5%. Cure rates among younger adults tend to be better, with anywhere from 25% to 70% achieving complete remission following chemotherapy.

Disease Characteristics

Leukemia is a diverse group of cancers that affect both blood-forming tissues and the blood cells themselves. While the disease mostly affects white blood cells, some forms of the disease attack other cell types.

In the case of AML, the term "acute" is used because the cancer is rapidly progressing, while "myeloid" refers to both bone marrow and the specific types of blood cells that bone marrow creates.

AML develops in an immature blood cell known as a myeloblast. These are the cells that, under normal circumstances, would mature into fully formed white blood cells such as granulocytes or monocytes. However, with AML, the myeloblasts will effectively be "frozen" in their immature state but continue to multiply unchecked.

Unlike normal cells that have a specific lifespan, cancer cells are essentially "immortal" and will continue to replicate without end.

With AML, the cancerous blood cells will eventually crowd out the normal ones and even interfere with the development of new white blood cells, red blood cells (erythrocytes), and platelets (thrombocytes).

AML is unlike its cousin acute lymphocytic leukemia (ALL) which affects another type of white blood cell known as a lymphocyte. While AML primarily affects older adults, ALL mainly strikes children between the ages of two and five.

Early Signs and Symptoms

The symptoms of AML are directly related to the displacement of normal blood cells by cancerous ones. The absence of the normal blood cells can leave a person vulnerable to infection and other illnesses that the body could otherwise prevent.

By way of illustration, white blood cells are central to the immune system. Red blood cells, by contrast, are responsible for carrying oxygen to and removing carbon dioxide from tissues, while platelets are key to the clotting of blood.

The depletion of any of these cells can lead to a cascade of symptoms, often non-specific and hard to diagnose. Examples include:

• A shortage of white blood cells can increase the risk of infections that won’t go away. These include symptoms related to the lack of leukocytes (leukopenia) or neutrophils (neutropenia).
• A shortage of red blood cells can lead to anemia which can manifest with symptoms of fatigue, paleness, shortness of breath, headaches, dizziness, and weakness.
• A shortage of platelets can lead to thrombocytopenia and the development of bleeding gums, excessive bruising or bleeding, or frequent or severe nosebleeds.

Later Stage Symptoms

As the disease progresses, other, more telling symptoms may begin to develop. Because leukemia cells are larger than normal white blood cells, they are more likely to get stuck in the smaller vessels of the circulatory system or to collect various organs of the body.

Depending on where the blockage occurs, a person may experience:

• Chloromas, a solid collection of cells that can develop into, alternately, a tumor-like mass outside of the bone marrow, a plaque-like rash, or painful bleeding and inflammation of the gums
• Leukostasis, a medical emergency in which the blockage can lead to symptoms similar to a stroke
• Sweet's syndrome, a painful skin rash appearing mostly on arms, head, legs, and trunk
• Deep vein thrombosis (DVT) in which a vein will become blocked, most often in the leg
• Pulmonary embolism (PE), the blockage of an artery in the lung
• Abdominal distention due to the accumulation of cells in the spleen and liver
• Meningeal leukemia manifesting with central nervous disorders such as headaches, vomiting, blurred vision, seizures, trouble balancing, and facial numbness

Less commonly, AML can affect the kidneys, lymph nodes, eyes, or testicles.

Causes and Risk Factors

There are a number of risk factors associated with AML. However, having one or even several of these factors doesn't mean that you will get leukemia. To date, we still don’t fully understand why some cells will suddenly turn cancerous while others don’t.

What we do know is that cancers are caused by a genetic coding error that can sometimes occur when a cell divides. We refer to this as a mutation. While the vast majority of mutations don’t lead to cancer, there are times when an error will inadvertently "turn off" something called a tumor suppressor gene which dictates how long a cell lives. If this happens, an abnormal cell can suddenly replicate out of control.

There are a number of risk factors associated with this:

• Smoking
• Occupational exposure to chemicals, especially to benzene
• Certain cancer chemotherapy drugs including cyclophosphamide, mechlorethamine, procarbazine, chlorambucil, melphalan, busulfan, carmustine, cisplatin, and carboplatin
• High radiation exposure, such as with cancer radiotherapy
• Having certain chronic blood disorders such as myeloproliferative disease (MPS) or myelodysplastic syndromes (MDS)
• Having certain congenital disorders such as Down syndrome, Fanconi anemia, and neurofibromatosis type 1

For reasons unknown, men are 67% more likely to get AML than women.

Diagnosis

If AML is suspected, the diagnosis will usually begin with a physical exam and a review the person's medical and family history. During the exam, the doctor will pay close attention to signs like extensive bruising, bleeding, infection, or any abnormality of the eyes, mouth, liver, spleen, or lymph nodes. A complete blood count (CBC) will also be performed to identify any abnormalities in the blood composition.

Based on these findings, the doctor may order a number of tests to confirm the diagnosis. These may include:

• Bone marrow aspiration: Bone marrow cells are extracted by inserting a long needle into a bone, usually around the hip
• Bone marrow biopsy: A larger needle is inserted deep into the bone to extract cells
• Lumbar puncture (spinal tap): A small needle is inserted between the bones of the spinal column to extract cerebrospinal fluid (CSF)
• Imaging tests: such as X-ray, ultrasound, or computed tomography (CT) scan
• Peripheral blood smear: Blood is examined under the microscope, typically with dyes that not only highlight the leukemia cells but help differentiate between AML and ALL
• Flow cytometry: Defensive proteins, called AML antibodies, are introduced into a blood or CSF sample to confirm the presence of AML cells
• Cytogenetics: Leukemia cells are "grown" in the lab and then examined under an electron microscope to identify the specific mutations by their chromosomal patterns

Leukemia Doctor Discussion Guide

Get our printable guide for your next doctor's appointment to help you ask the right questions.

Download PDF

Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life.

Sign Up

You're in!

Thank you, {{form.email}}, for signing up.

There was an error. Please try again.

Staging

Cancer staging is performed to determine the extent to which a cancer has spread. This, in turn, helps the doctor determine the appropriate course of treatment so that the person is neither undertreated nor overtreated. The staging also helps predict how long a person is likely to survive following treatment.

Because AML does not involve the formation of a malignant tumor seen in other types of cancer, it cannot be staged with the classic TNM (tumor/lymph node/malignancy) methodology.

There are two different methodologies currently used to stage AML: the French-American-British (FAB) classification of AML and the World Health Organization (WHO) classification of AML.

FAB Classification

The French-American-British (FAB) classification was developed in the 1970s and stages the disease based on the type and maturity of the affected cell.

The rationale for the staging is simple: AML will typically follow a pattern wherein immature myeloblasts are the first cells to be affected. As the disease progresses, it will begin to affect myeloblasts in later stages of maturation and then progress to mature white blood cells (such as monocytes and eosinophils) before moving to red blood cells (erythrocytes) and finally megakaryoblasts (immature platelet cells).

This progression will provide the pathologist the information needed to know how advanced the cancer is.

FAB staging ranges from M0 (for early AML) to M7 (for advanced AML) as follows:

• M0: Undifferentiated acute myeloblastic leukemia
• M1: Acute myeloblastic leukemia with minimal maturation
• M2: Acute myeloblastic leukemia with maturation
• M3: Acute promyelocytic leukemia
• M4: Acute myelomonocytic leukemia
• M4 eos: Acute myelomonocytic leukemia with eosinophilia
• M5: Acute monocytic leukemia
• M6: Acute erythrocytic leukemia
• M7: Acute megakaryoblastic leukemia

WHO Classification

The World Health Organization developed a new means of classifying AML in 2008. Unlike the FAB system, the WHO classification takes into account the specific chromosomal mutations found during a cytogenetic analysis. It also factors in the medical conditions that may improve or worsen the outlook (prognosis) of the affected individual.

The WHO system is far more dynamic in its assessment of the disease and can be broadly broken down as follows:

• AML with recurrent genetic abnormalities (meaning specific, characteristic genetic mutations)
• AML with myelodysplasia-related changes (meaning the presence of MDS, MDP, or other myeloblastic disorders)
• Therapy-related myeloid neoplasms (meaning related to prior chemotherapy or radiation therapy)
• Myeloid sarcoma (meaning AML accompanied by a chloroma)
• Myeloid proliferations related to Down syndrome
• Blastic plasmacytoid dendritic cell neoplasm (an aggressive form of cancer characterized by skin lesions)
• AML not otherwise categorized (essentially the seven-stage FAB system with two additional disease classifications)

Treatment

If diagnosed with AML, the form and duration of treatment will be largely determined by the stage of the cancer and the general health of the individual.

Typically speaking, treatment will begin with chemotherapy. This may include older generation drugs that are can affect both cancerous and noncancerous cells and newer generation targeted drugs that zero in on the cancer cells alone.

The standard chemotherapy regimen is referred to as "7+3" because a chemotherapy drug known as cytarabine is given as a continuous intravenous (IV) infusion for seven days followed by three consecutive days of another drug known as anthracycline. Up to 70% of people with AML will achieve remission following "7+3" therapy.

With that being said, a small number of leukemia cells will likely remain following chemotherapy, leading to relapse in the majority of cases. To avoid this, doctors will prescribe ongoing therapy based on the person’s post-treatment results and health status.

In persons with good diagnostic indicators, treatment may only involve three to five courses of intensive chemotherapy, referred to as consolidated chemotherapy. The IDH1 inhibitor Tibsovo (ivosidenib tablets) may be recommended in combination with other treatments for people 75 and older with other conditions that rule out the use of intensive induction chemotherapy, or those with relapsed or refractory AML.

For those at high risk of relapse, other, more aggressive treatments may be required including a stem cell transplant if a donor can be found. Less commonly, surgery or radiation therapy may be recommended.

Because AML chemotherapy tends to have lead to severe immune suppression, elderly patients may not able to tolerate treatment and may instead be given less intensive chemo or palliative care.

Survival

The outlook for a person who has undergone AML treatment can vary significantly based on the stage of cancer at the time of the diagnosis. But, there are other factors that can also predict the likely outcome. Among them:

• Persons diagnosed with MDS and MPD have a survival time ranging from nine months to 11.8 years depending on the severity of the disorder.
• Certain chromosomal mutations identified by cytogenetics can lead to five-year survival rates of as low as 15% to as high as 70%.
• Persons over 60 who have elevated levels of lactate dehydrogenase (indicating extensive tissue damage) generally have poorer outcomes.

Overall, the average cure rate of AML is between 20% and 45%. Sustained remission rates tend to be highest in younger people who are more able to tolerate treatment.

A Word From Verywell

If you have been diagnosed with AML, you will be faced with emotional and physical challenges that may be hard to overcome. Don’t go it alone. Your chances of successfully coping will be far improved if you build a support network made up of loved ones, healthcare professionals, and others who have either gone through or are going through cancer treatment.

Even after you have undergone treatment, fears about relapse may linger for months or even years. With support, you will eventually overcome these concerns and learn to monitor your health with regular doctor visits. Generally speaking, if relapse hasn’t occurred within a few years, it is unlikely that AML will ever return.

While there is nothing that you can take to prevent a relapse, a healthy lifestyle can greatly improve your odds. This includes imparting good eating habits, exercising regularly, stopping smoking, and getting plenty of rest to avoid stress and fatigue.

In the end, it is important to take things one day at a time and to have someone you can turn to if ever you need support.