Leukemia is an umbrella term for cancers of the blood cells. There are several types of leukemia, each of which is classified based on the type of blood cells that are affected and whether the leukemia is acute or chronic. Acute leukemias have a rapid onset and progress quickly, whereas chronic leukemias develop slowly and progress over several years.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. It tends to affect older people—the average age at diagnosis is 68—though it can also occur in adolescents and children. According to the National Cancer Institute, it accounts for 1.1% of all cancer cases in the U.S., and an estimated 20,240 people in the U.S. were diagnosed with it in 2021.

In people with AML, symptoms usually develop and progress rapidly over the course of a few weeks. Because it is an aggressive cancer, treatment should start as soon as it is diagnosed.

“Many patients with AML have the prospect of cure, but this is a heterogeneous disease for which the treatments and patient journey can vary greatly,” says Smilow Cancer Hospital hematologist Rory Shallis, MD. “The low blood counts that can come with AML—and the treatments directed against it—are addressed with blood product transfusions, vigilance for infection prevention and treatment, and other layers of support to help patients realize the potential benefits of therapy." 

This is an encouraging time for the treatment of AML, for which many ‘targeted’ therapies are now standards of care and many more are in development with promising initial results, he adds.

Leukemia begins in the bone marrow—the spongy tissue at the center of the bones—where new blood cells (white blood cells, red blood cells, and platelets) are produced. This process is tightly regulated to ensure that new blood cells are healthy. In patients with leukemia, genetic changes (mutations) disrupt this regulation, resulting in the production of large numbers of abnormal blood cells that are unable to perform their usual functions. 

In AML, the bone marrow produces large numbers of abnormal myoblasts, a type of white blood cell that does not mature, leading to a shortage of infection-fighting white blood cells. Because of this, people with AML are more prone to infections.

These leukemia cells enter the blood stream and can spread to other parts of the body. As the number of abnormal myoblasts increases, they accumulate in the bone marrow and crowd out healthy blood cells. Eventually, the bone marrow can no longer produce enough healthy red blood cells and platelets to meet the body’s needs. 

Because red blood cells carry oxygen to tissues and organs around the body, people with low levels of red blood cells may have shortness of breath and feel tired. Platelets help stop bleeding by facilitating the formation of blood clots, and people with low numbers of them may bruise and bleed easily. 

Unlike many other kinds of cancer, AML usually does not form tumors. In rare cases, though, a tumor called a myeloid sarcoma may form. They can affect any part of the body.

There are several subtypes of AML, each of which is classified based on characteristics of the leukemia cells involved, including the presence of certain gene or chromosome abnormalities, proteins, and other features. AML subtypes may cause different symptoms, and some have a more favorable prognosis than others.

The World Health Organization (WHO) divides AML into several categories, each of which is made up of multiple subtypes of AML. These categories include:

• AML with recurrent genetic abnormalities (these subtypes have certain gene or chromosomal changes)
• AML with myelodysplasia-related changes (these subtypes occur in people who have myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms, or abnormal-looking blood cells)
• Therapy-related myeloid neoplasms (these subtypes arise due to previous chemotherapy or radiation therapy)
• AML not otherwise specified (these are subtypes that do not fit into other categories)
• Myeloid sarcomas (people with these AMLs have a type of tumor called a myeloid sarcoma)
• Myeloid proliferations related to Down syndrome (these subtypes occur in people with Down syndrome)

Treatment may also vary by subtype. Acute promyelocytic leukemia (APL), for instance, is a subtype of AML in which genes from one chromosome switch places with genes on another chromosome. People with APL may have severe bleeding and impaired blood clotting. APL is treated with different drugs than other forms of AML.   

Acute myeloid leukemia is caused by genetic abnormalities or changes. These may be inherited, occur spontaneously, or arise due to certain environmental exposures.

Risk factors for AML include:

• Advanced age
• Male sex
• Long-term exposure to benzene
• Radiation exposure (i.e., nuclear radiation, radiation therapy)
• Smoking
• Previous use of certain chemotherapy drugs (i.e., alkylating drugs and topoisomerase II inhibitors)
• Personal history of a myeloproliferative neoplasm or a myelodysplastic syndrome (MDS)
• Family history of AML
• Having certain inherited genetic disorders, including Down syndrome, Fanconi anemia, Ataxia-telangiectasia, Kostmann syndrome, and Klinefelter syndrome, among others

Symptoms may include:

• Feeling tired/weakness
• Fever
• Shortness of breath
• Easy bruising and/or bleeding
• Frequent nosebleeds and/or bleeding gums
• Heavy menstrual flow in women
• Unintentional weight loss
• Pale skin
• Nosebleeds and/or bleeding gums
• Frequent infections
• Headache
• Bone and joint pain
• Tiny red spots on skin (caused by bleeding under the skin)
• Small bumps, nodules, and/or rash on skin
• Vision problems
• Abdominal swelling

Diagnosing AML usually involves a review of the patient’s medical history, a physical exam, and one or more diagnostic tests.

The doctor will begin to make a diagnosis by asking about symptoms and risk factors linked to AML. During the physical exam, the doctor will check the skin for bruising or other changes indicative of AML. He or she will also examine the patient’s eyes and mouth, feel the abdomen for evidence of an enlarged spleen or liver, evaluate nervous system function, and check for enlarged lymph nodes.

Additional testing is usually necessary to confirm the diagnosis. These tests may include:

• Blood tests. The doctor will order a complete blood count (CBC) and peripheral blood smear. Together these tests allow doctors to measure the levels of different types of blood cells and assess their shape and size.
• Bone marrow aspiration and biopsy. To perform a bone marrow aspiration, a doctor inserts a needle into the hip bone and uses it to remove a sample of fluid from the bone marrow. For a bone marrow biopsy, a small piece of spongy bone marrow tissue is removed using a needle. These two procedures are often performed together. A pathologist examines the tissue samples to see if leukemia cells are present.
• Molecular and genetic testing. Molecular and genetic tests are used to analyze proteins, genes, and chromosomes in AML cells. They help doctors determine the subtype of AML. These tests may include:
  • Cytogenetic testing. In cytogenetic testing, leukemia cells are examined under a microscope to identify chromosome abnormalities.
  • Molecular genetic testing. Additional genetic tests may be used to detect specific genetic changes that are associated with different subtypes of AML.
  • Immunophenotyping. Lab tests, including flow cytometry and immunohistochemistry, are used to identify certain markers on AML cells.

If AML is diagnosed, additional tests may be necessary to assess how it is affecting other parts of the body. These tests may include: 

• Lumbar puncture (spinal tap). This test is used to determine whether AML cells have spread to the tissue around the brain and spinal cord.
• Imaging tests. Imaging studies, such as computed tomography (CT) scans, magnetic resonance imaging (MRI) studies, ultrasounds, and X-rays, help doctors assess whether and how the disease is affecting different areas of the body.

Doctors determine the best course of treatment based on various factors, including the subtype of AML, as well as the patient’s age and general health. In general, though, treatment of AML is divided into two phases:

• Induction chemotherapy. Sometimes known as “remission induction chemotherapy,” in this initial phase of treatment patients are given chemotherapy drugs with the aim of killing as many leukemia cells as possible. The goal is to put the cancer into complete remission. In complete remission, the cancer cells are undetectable (though some leukemia cells may remain) and the patient does not experience any symptoms.

• Consolidation therapy. Also known as “postremission consolidation therapy,” this second phase of treatment begins once AML is in remission. The goal of this phase is to kill leukemia cells that remain in the body, thereby lowering the risk that the cancer will return. Consolidation therapy involves chemotherapy or stem cell transplantation.

In addition to chemotherapy and stem cell transplantation, other treatments for AML may be used, including:

• Targeted therapy, which uses drugs designed to target specific components found in cancer cells but not healthy cells. These drugs can target specific subtypes of AML.

• Radiation therapy. This treatment kills cancer cells by exposing them to radiation. It is not a main treatment for AML, but it is used prior to stem cell transplantation to reduce the size of myeloid sarcomas, and to treat AML that has spread to the brain or spinal cord.

Sometimes, AML does not respond well to treatment or comes back after a period of remission. In these cases, in addition to the therapies discussed above, patients may be offered the option of joining a clinical trial or beginning palliative care. 

Subtypes of AML may require a different course of treatment. APL, for example, is treated with drugs called differentiation agents. In addition to the induction and consolidation phases of therapy, APL treatment has a third phase called maintenance therapy. In this phase, patients are given low doses of ATRA (all-trans retinoic acid) for a year or two following initial treatment. 

The outlook for people who have AML depends on several factors, including the patient’s age, general health, and whether they have previously been treated with chemotherapy for another medical condition. In general, younger, healthier patients who have no history of chemotherapy have better outcomes. The subtype of AML, whether the cancer cells have certain genetic changes, and a number of other factors also affect the prognosis.

The five-year survival rate for adults with AML in the U.S. is 29.5%. For children and adolescents aged 19 or younger, the five-year survival rate is 66%. APL has a more favorable prognosis than AML and, in the majority of cases, can be cured.

“Being a patient at Yale means getting more than the ‘standard of care,’” says Dr. Shallis. “When someone is either diagnosed with or has a concern for AML, they are seen by an AML specialist who performs a thorough evaluation in conjunction with other members of our team comprised not only of physicians, but also of advanced practice providers, nurses, social workers, nutritionists, and clinical trial staff, among others. They span across other specialties from Palliative Care to Bone Marrow Transplant.”

Every patient is evaluated for a clinical trial, which is personalized to disease and patient specifics. Such trials also have the potential to offer access to cutting-edge agents that may be game-changers in the near future, he adds.

“Although Yale rests between two major metropolitan centers with cancer centers with whom we collaborate and have many of the same clinical trials, resources and patient outcomes, our family-like atmosphere is hard to ignore. When combined with our excellent tools to help patients along their journey with AML, Yale is definitely a special place to seek and receive care,” says Dr. Shallis.