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Acute Myelomonocytic Leukemia (AMML): An Overview

Medically reviewed by Mark Levin, M.D.
Written by Maureen McNulty
Posted on April 15, 2021

Acute myelomonocytic leukemia (AMML) is a rare blood cancer. It is a subtype of acute myeloid leukemia or acute myelogenous leukemia (AML). AMML makes up about 5 percent to 10 percent of AML cases. It also accounts for around 3 percent of all childhood leukemias.

What Is Acute Myelomonocytic Leukemia?

Acute myeloid leukemia is cancer that develops from a form of white blood cells called myeloid cells. There are several types of myeloid cells, and they have a few different roles in the body, including protecting the body from infections and helping to heal damage.

AML is often categorized into subtypes based on which type of myeloid cell the cancer develops from. Acute myelomonocytic leukemia can affect a few different types of myeloid cells, including:

  • Monocytes — Destroy and remove germs, get rid of dead cells, and boost the immune system
  • Neutrophils — Produce molecules that help kill germs
  • Eosinophils — Are involved in the body’s responses to infections, asthma, and allergies

People with AMML have too many abnormal monocytes and neutrophils. Less commonly, people with AMML also have too many eosinophils (eosinophilia). The abnormal myeloid cells in AMML are called myeloblasts. They are immature, look and act differently than normal cells, and grow and multiply too quickly.

Doctors use a few different systems to categorize AML subtypes. One of these systems is called the French-American-British (FAB) classification. Under this system, AMML is called M4. For this reason, AMML is sometimes referred to as FAB subtype M4 or as AML-M4. When people with AMML also have eosinophilia, their FAB subtype is called M4 eos. Another system sometimes used to classify AML subtypes is the World Health Organization (WHO) system. Under this system, AMML falls under the category of “AML not otherwise specified.”

What Causes AMML?

AMML forms when cells become damaged, leading to gene changes that cause cells to grow out of control. Being exposed to certain factors that damage a cell’s genes can increase a person’s risk of AMML. These risk factors include:

  • Exposure to tobacco, marijuana, or alcohol while in the womb
  • Exposure to chemicals like benzene or pesticides
  • Radiation
  • Chemotherapy

Having certain diseases can also lead to an increased risk of developing AMML, including:

  • Aplastic anemia
  • Myelodysplastic syndrome
  • Paroxysmal nocturnal hemoglobinuria
  • Down syndrome
  • Fanconi anemia
  • Bloom syndrome
  • Ataxia telangiectasia
  • Li-Fraumeni syndrome

Most people who are exposed to these risk factors or have these diseases never develop cancer. It’s not clear why some people develop cancer and others don’t. There is no way to fully prevent cancer or to know what caused any individual case of leukemia.

Symptoms of Acute Myelomonocytic Leukemia

Between 80 percent and 99 percent of the people who have AMML have low levels of red blood cells and platelets. Red blood cells carry oxygen to all the cells of your body. When you don’t have enough of these cells (the condition is called anemia), you may experience:

  • Feeling tired
  • Irregular heart rhythms
  • Lightheadedness
  • Pale skin
  • Cold hands and feet

Platelets are responsible for clotting your blood. They help keep you from losing too much blood from a cut or injury. When you don’t have enough platelets, you may have symptoms like bleeding gums, petechiae (small red spots in the skin), bruises, heavy periods, or blood in the urine, vomit, or stool.

Other signs and symptoms of AMML include:

  • Feelings of weakness
  • Fever
  • Shortness of breath
  • Trouble focusing or thinking clearly
  • Gingival hyperplasia (overgrowth of the gums)
  • Swelling of the abdomen
  • Swelling of the lymph nodes (small glands in the neck, groin, abdomen, and armpits)

Diagnosing Acute Myelomonocytic Leukemia

If your doctor thinks there is a chance you have AMML, they may have you undergo several tests. One of the first tests is a complete blood count (CBC). This test uses a blood sample to measure the levels of each of your different types of blood cells. It can show whether your red blood cell, white blood cell, or platelet numbers are too high or too low. Other blood tests can also be used to look more closely at potential cancer cells.

You may also need to have a bone marrow aspiration and biopsy. These tests examine your bone marrow, the spongy tissue found inside your bones where all your blood cells are created. During this procedure, a doctor will likely use a needle to remove bone marrow cells and fluid from your hip bone.

Once your blood and bone marrow samples are collected, they will undergo further testing in a laboratory. These tests can help doctors see if there are cancer cells present in the bone marrow, and if so, what type of cancer cells they are. Tests may include cytogenetic tests that identify changes in the chromosomes (pieces of DNA that contain your genes). For example, some people with AMML have a chromosome change called inv(16)(p13q22), in which part of a chromosome is incorrectly flipped. Learning which gene changes are found in your cancer cells can provide clues that indicate which treatments may be most helpful.

Immunophenotyping tests can provide additional information about your leukemia cells. These tests can read the types of proteins that are found on the surface of the cells. This information helps doctors see exactly which cell types became cancerous.

AMML Treatment

Most people with AMML are treated with chemotherapy. Most people with different subtypes of acute myeloid leukemia use the same types of chemotherapy. These chemotherapies often include anthracycline drugs like Cerubidine (daunorubicin) or Idamycin (idarubicin), which block cancer cells from multiplying. Chemotherapy may also include Cytosar-U (cytarabine), which damages the DNA of cancer cells and prevents the cells from healing themselves.

Some people with AMML also receive targeted therapies. These drugs can specifically attack cancer cells while mostly leaving other normal cells alone. One common targeted therapy used for AMML is Mylotarg (Gemtuzumab ozogamicin). This drug has been approved by the U.S. Food and Drug Administration (FDA) to treat AML cells that contain a protein called CD33. Immature AMML cells often contain this protein. Gemtuzumab ozogamicin has two parts. One part is an antibody that attaches to CD33. The other part is a chemotherapy drug. This drug can find cancer cells and deliver chemotherapy directly to them.

Phases of Leukemia Treatment

People with AMML receive therapy in a few different phases. The first phase, called induction therapy, attempts to get rid of most of the cancer cells. It usually includes chemotherapy and sometimes targeted therapy. The next phase is consolidation therapy, which aims to kill any remaining cells. Consolidation therapy often includes high-dose cytarabine and an allogeneic stem cell transplantation. During a stem cell transplant, you receive an infusion of healthy stem cells, which then make all of the different types of blood cells. A transplant can help you build up your levels of normal blood cells and prevent cancer from returning.

People with AMML who are older or who have other health problems may not be able to receive standard consolidation therapy, which can be aggressive. These people may use lower doses of cytarabine, or receive different chemotherapy drugs like Onureg (azacitidine) or Hydrea (hydroxycarbamide).

If you have AMML, you may also be able to take part in clinical trials. During a clinical trial, you may be able to receive a new type of treatment or try a different treatment plan. Talk to your health care team to learn more about clinical trials that may be available for you.

What Is the Outlook for AMML?

Across all subtypes of acute myeloid leukemia, 28.7 percent of people live for at least five years after being diagnosed. Younger people tend to have a better outlook. More than 80 percent of people younger than 60 years go into remission (have no more signs of disease). However, less than half of people over 60 years old achieve remission. People with AMML who have the inv(16) chromosome change also tend to have a better outlook. To better understand how your characteristics affect your prognosis, talk to your doctor.

Connect With Others Who Understand

If you or a loved one has recently been diagnosed with acute myelomonocytic leukemia, consider reaching out to others who share your journey. It can be helpful to know that you are not alone. At MyLeukemiaTeam, more than 8,000 people living with leukemia share their stories, ask questions, and give each other advice.

Have you or a loved one been diagnosed with acute myelomonocytic leukemia? Share your experience in the comments below, or on your Activities page.

Posted on April 15, 2021
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Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here

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