Acute Myelogenous Leukemia

What is acute myelogenous leukemia?

Acute myelogenous leukemia (AML), also called acute myeloid leukemia, is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside bones where blood cells are made. In AML, the marrow produces large numbers of abnormal, immature white blood cells called myeloblasts, or blasts. These blasts do not mature into healthy cells and cannot fight infection. They multiply quickly and crowd out normal red blood cells, white blood cells and platelets (the cell fragments that help blood clot).

The word acute means the disease develops quickly and usually needs prompt treatment. Myelogenous (or myeloid) refers to the type of cell involved: the myeloid line, which normally produces red blood cells, platelets and most white blood cells other than lymphocytes.

AML is the most common type of acute leukemia in adults. It can occur at any age, but it is more often diagnosed in older adults, and the risk rises with age. It also occurs in children, although childhood leukemia is more often of the lymphoblastic type. AML is somewhat more common in men than in women.

Doctors classify AML into subtypes based on how the cells look under a microscope and on specific genetic changes inside the leukemia cells. These subtypes matter because they help guide treatment decisions and give doctors a sense of how the disease may behave.

Acute myelogenous leukemia symptoms

The symptoms of acute myelogenous leukemia usually come from a shortage of normal blood cells rather than from the leukemia cells themselves. Because AML develops quickly, symptoms often appear over days or weeks and may at first resemble the flu or another common illness.

• Fatigue and weakness from a low red blood cell count (anemia)
• Pale skin
• Shortness of breath, especially with activity
• Frequent or persistent infections because there are too few healthy white blood cells
• Fever, with or without an obvious infection
• Easy bruising or bleeding, such as nosebleeds, bleeding gums or heavy menstrual periods, due to low platelets
• Tiny red or purple spots on the skin (petechiae) caused by bleeding under the skin
• Bone or joint pain as leukemia cells build up in the marrow
• Unexplained weight loss or loss of appetite
• Night sweats

Some people notice swelling of the gums, swollen lymph nodes (small glands that are part of the immune system), or a feeling of fullness under the ribs from an enlarged liver or spleen. Less commonly, leukemia cells can collect in the skin, forming lumps, or spread to the brain and spinal cord, causing headaches, vision changes or confusion.

Symptoms may vary by subtype. In acute promyelocytic leukemia (APL), a specific AML subtype, bleeding and clotting problems can be severe and appear early. In people with a very high number of blast cells in the blood, the blood can become thick, which may cause breathing difficulty or neurological symptoms. AML is not usually described in stages the way solid tumors are. Instead, doctors describe it as newly diagnosed, in remission (no detectable disease on standard tests) or relapsed (returned after treatment).

Causes and risk factors

Acute myelogenous leukemia causes are not fully understood. The disease begins when a blood-forming cell in the bone marrow acquires changes (mutations) in its DNA, the genetic material that tells cells how to grow and divide. These changes cause the cell to keep dividing and to stop maturing normally. In most people, doctors cannot identify a specific reason why these mutations occurred. The genetic changes are almost always acquired during life rather than inherited from a parent.

Several factors are known to increase the risk of developing AML, although most people with these risk factors never develop the disease, and many people with AML have no known risk factors.

• Older age. Risk increases with age, and most people are diagnosed later in life.
• Previous cancer treatment. Certain chemotherapy drugs and radiation therapy used for other cancers can damage bone marrow cells and lead to AML years later. This is sometimes called therapy-related AML.
• Exposure to radiation. High doses of radiation, such as from nuclear accidents, are linked to a higher risk.
• Exposure to certain chemicals. Long-term exposure to benzene, a chemical found in some industrial settings and in cigarette smoke, is a recognized risk factor.
• Smoking. Tobacco use is associated with a higher risk of AML.
• Other blood disorders. Conditions such as myelodysplastic syndromes (in which the marrow makes poorly formed cells), myeloproliferative disorders (in which the marrow makes too many cells) and aplastic anemia can progress to AML.
• Genetic syndromes. Inherited conditions such as Down syndrome, Fanconi anemia and Li-Fraumeni syndrome raise the risk, particularly in children and young adults.
• Family history. Having a close relative with AML slightly increases risk, although familial AML is uncommon.

AML is not contagious. It cannot be passed from one person to another.

Acute myelogenous leukemia diagnosis

Because the early symptoms of AML are similar to those of many minor illnesses, the diagnosis often begins when a routine or symptom-prompted blood test shows unusual results. Confirming acute myelogenous leukemia requires examining the bone marrow and the leukemia cells themselves. Your doctor may use several of the following tests.

• Medical history and physical examination. The doctor asks about symptoms, past illnesses, cancer treatments and chemical exposures, and checks for bruising, pale skin, swollen lymph nodes and an enlarged liver or spleen.
• Complete blood count (CBC). This blood test measures red cells, white cells and platelets. In AML, red cells and platelets are often low, while the white cell count may be high, low or normal. A blood smear, in which a drop of blood is examined under a microscope, may show blast cells.
• Bone marrow aspiration and biopsy. This is the key test for diagnosis. Using a needle, usually inserted into the back of the hip bone after numbing the skin, the doctor removes a small sample of liquid marrow (aspiration) and a small core of bone with marrow (biopsy). A diagnosis of AML is generally made when blast cells make up 20 percent or more of the cells in the marrow or blood, or when certain specific genetic changes are found regardless of the blast percentage.
• Flow cytometry (immunophenotyping). This laboratory test identifies proteins on the surface of the cells to confirm that they are myeloid cells and to distinguish AML from other leukemias.
• Cytogenetic testing. This examines the chromosomes (the structures that carry DNA) inside leukemia cells for missing, extra or rearranged pieces.
• Molecular genetic testing. These tests search for mutations in specific genes such as FLT3, NPM1, IDH1 and IDH2. The results help doctors classify the subtype, estimate how the disease may respond to treatment and decide whether a targeted drug may be appropriate.
• Lumbar puncture (spinal tap). In some cases, a sample of the fluid surrounding the brain and spinal cord is checked for leukemia cells, particularly if there are neurological symptoms.
• Imaging tests. X-rays, CT scans or ultrasound are not used to diagnose AML itself but may be ordered to check for infection, an enlarged spleen or other complications. An echocardiogram (ultrasound of the heart) is often done before certain chemotherapy drugs are given.

Results from these tests are combined to place the disease into a risk group, often described as favorable, intermediate or adverse. This grouping does not predict the outcome for any individual person, but it helps the care team recommend a treatment plan.

Acute myelogenous leukemia treatment options

AML usually requires treatment to begin soon after diagnosis. Acute myelogenous leukemia treatment options depend on the subtype, the genetic features of the leukemia cells, the person’s age and general health, and whether the disease is newly diagnosed or has returned. Care is typically coordinated by a hematologist (a doctor specializing in blood disorders) or a medical oncologist (a doctor specializing in cancer drug treatment). At Acibadem, this care is managed within the Medical Oncology Department in cooperation with hematology and transplant teams.

Treatment is generally described in phases.

• Induction therapy. The first phase aims to kill as many leukemia cells as possible and bring the disease into remission, meaning no leukemia cells are found on standard tests and normal blood cell production resumes. Intensive induction usually involves a combination of chemotherapy drugs given in the hospital over several days, followed by a stay of several weeks while the marrow recovers. During this time, blood counts are very low, and people need transfusions and careful protection from infection.
• Consolidation (post-remission) therapy. Even when remission is achieved, some leukemia cells usually remain. Consolidation uses additional cycles of chemotherapy, or a stem cell transplant, to reduce the chance of relapse.
• Maintenance therapy. In some situations, lower-intensity medication may be continued for a longer period to help keep the disease in remission.

The main types of treatment include the following.

• Chemotherapy. Medicines that kill rapidly dividing cells remain the foundation of AML treatment. They are usually given through a vein, often through a central line (a thin tube placed in a large vein). Common side effects include nausea, hair loss, mouth sores, fatigue and a high risk of infection and bleeding while counts are low.
• Targeted therapy. These drugs act on specific genetic changes in the leukemia cells, such as FLT3 or IDH mutations, or on proteins that help the cells survive. They may be combined with chemotherapy or used on their own, depending on the situation.
• Lower-intensity therapy. For older adults or people with other serious health conditions who may not tolerate intensive chemotherapy, doctors may recommend gentler regimens, often combining a lower-dose chemotherapy drug with a targeted medicine.
• Differentiation therapy for APL. The acute promyelocytic leukemia subtype is treated differently, usually with drugs that make the abnormal cells mature normally rather than killing them outright. Prompt recognition of this subtype is important because of its bleeding risk.
• Stem cell (bone marrow) transplant. A transplant replaces the diseased marrow with healthy blood-forming stem cells, most often from a matched donor (an allogeneic transplant). It is usually given after high-dose chemotherapy and is considered for people whose leukemia has a higher risk of returning, or whose disease has relapsed. It carries significant risks, including infection and graft-versus-host disease, in which donor cells attack the recipient’s tissues, so it is not suitable for everyone.
• Supportive care. Transfusions of red cells and platelets, antibiotics and antifungal medicines, and drugs to control nausea are an essential part of treatment throughout all phases.
• Clinical trials. Because AML research is active, your doctor may discuss taking part in a clinical trial testing new medicines or combinations.

Surgery has no role in treating AML itself, since the disease is spread throughout the blood and marrow rather than located in one place. Radiation therapy is used only in limited situations, such as preparing for a transplant or treating leukemia that has spread to the brain. Observation without treatment is rarely appropriate for acute leukemia, although in some frail patients the focus of care may be comfort and quality of life rather than cure. Rehabilitation, including physical therapy and nutritional support, is often helpful during and after treatment to rebuild strength.

Living with acute myelogenous leukemia and outlook

The outlook for people with AML varies widely. It depends heavily on the genetic features of the leukemia, the person’s age and general health, and how the disease responds to the first course of treatment. Younger adults and those with favorable-risk genetic changes generally have a better chance of long-term remission, while older adults and those with adverse-risk features often face a harder course. Doctors tend to use the term remission rather than cure for several years after treatment, because relapse remains possible. When the disease stays in remission for a long period, the likelihood of it returning decreases.

Treatment for AML is demanding. Many people spend weeks in the hospital during induction and need frequent follow-up visits afterward. Fatigue, emotional strain and worry about relapse are common. After treatment ends, regular blood tests and sometimes marrow examinations are scheduled to monitor for recurrence and to check for late effects of therapy, such as heart or fertility problems.

Practical steps that many patients find helpful include following infection-prevention advice closely while blood counts are low, eating a balanced diet when appetite allows, staying as active as energy permits, and keeping open communication with the care team about side effects. Counseling and peer support groups can help patients and families cope with the uncertainty that comes with this diagnosis. Your care team can provide guidance tailored to your situation.

Frequently asked questions

What is acute myelogenous leukemia in simple terms?

Acute myelogenous leukemia is a fast-growing cancer that starts in the bone marrow, where blood is made. Abnormal immature white blood cells multiply and prevent the marrow from producing enough healthy red cells, white cells and platelets. This leads to anemia, infections and bleeding problems. It is considered a medical emergency that usually needs treatment soon after diagnosis.

What are the first symptoms of acute myelogenous leukemia?

Early acute myelogenous leukemia symptoms are often vague and flu-like: tiredness, fever, pale skin, shortness of breath and frequent infections. Easy bruising, nosebleeds, bleeding gums and small red skin spots are also common. Because these symptoms overlap with many minor illnesses, the disease is frequently discovered when a blood test shows abnormal counts.

What causes acute myelogenous leukemia?

In most cases, doctors cannot pinpoint a cause. AML develops when a bone marrow cell acquires genetic mutations that make it divide uncontrollably. Known risk factors include older age, previous chemotherapy or radiation, exposure to benzene, smoking, certain inherited syndromes and pre-existing blood disorders such as myelodysplastic syndromes. Many people with AML have none of these risk factors.

How is acute myelogenous leukemia diagnosed?

Acute myelogenous leukemia diagnosis usually starts with a complete blood count and blood smear. It is confirmed with a bone marrow aspiration and biopsy, in which marrow is examined for blast cells. Additional laboratory tests, including flow cytometry, chromosome analysis and gene mutation testing, identify the subtype and help guide treatment.

What are the treatment options for acute myelogenous leukemia?

Acute myelogenous leukemia treatment options typically include intensive chemotherapy to induce remission, followed by consolidation chemotherapy or a stem cell transplant. Targeted drugs may be added when specific mutations are present, and lower-intensity regimens may be used for people who cannot tolerate intensive therapy. Supportive care such as transfusions and infection prevention is part of every plan.

Can acute myelogenous leukemia be cured?

Some people with AML achieve a lasting remission and are eventually considered cured, particularly those with favorable genetic features who respond well to initial treatment. For others, the disease may return or may not respond fully. Outcomes vary considerably, and your doctor can discuss what the features of your particular disease mean for you.

Is acute myelogenous leukemia hereditary?

AML is usually not inherited. The genetic changes that cause it are typically acquired during a person’s lifetime and are not passed to children. A small number of families carry inherited gene changes or syndromes that increase risk. If several relatives have had blood cancers, your doctor may suggest genetic counseling.

When to see a doctor

Many of the symptoms described on this page can be caused by conditions that are far less serious than leukemia. However, persistent or unexplained symptoms should always be evaluated by a doctor, especially when several occur together. A simple blood test can often provide reassurance or point toward the need for further testing.

Seek medical attention promptly if you notice any of the following:

• Fatigue or weakness that lasts more than a couple of weeks without a clear reason
• Frequent infections or infections that keep coming back
• Unexplained bruising, bleeding gums or nosebleeds that are hard to stop
• Tiny red or purple spots on the skin
• Unexplained fever or night sweats
• Unexplained weight loss or loss of appetite
• Persistent bone pain

For people already diagnosed with or being treated for AML, the following are urgent warning signs that need immediate medical care, as they may indicate a serious infection, bleeding or another complication:

• Fever of 38 degrees Celsius (100.4 degrees Fahrenheit) or higher, or chills and shaking
• Bleeding that does not stop, blood in the urine or stool, or vomiting blood
• Severe or sudden headache, confusion, vision changes or difficulty speaking
• Difficulty breathing or chest pain
• Signs of infection at a central line site, such as redness, swelling, pain or discharge
• Severe abdominal pain or persistent vomiting that prevents you from keeping fluids down

Because blood counts can drop rapidly during and after treatment, people with AML are usually given specific instructions about when and how to seek emergency care. Following those instructions closely is an important part of staying safe during treatment.