Acute Myeloid Leukemia

Acute Myeloid Leukemia

Also called: Acute Nonlymphoblastic Leukemia, Acute Granulocytic Leukemia, Acute Myelogenous Leukemia, Acute Myelocytic Leukemia, AML, Acute Nonlymphocytic Leukemia, Acute Myeloblastic Leukemia, AML Leukemia

Reviewed By:
Martin E. Liebling, M.D., FACP

Summary

Acute myeloid leukemia (AML) is a form of leukemia, or cancer of the body’s blood-forming cells. It is the most common form of acute leukemia in adults. Also known as acute myelogenous leukemia, AML affects the body’s blood making system, including:

  • Bone marrow. Bone marrow is the soft, inner component of bones. All forms of blood cells are produced in the bone marrow including:

    • White blood cells (cells that fight infection).

    • Red blood cells (cells that carry oxygen to tissues all over the body).

    • Platelets (cells that help develop blood clots and control bleeding).

  • Lymphatic system. A network of glands, organs and ducts responsible for filtering and extracting fluid from tissues, as well as producing and storing the cells needed by the body to fight infections and diseases.

In patients with AML, the bone marrow usually manufactures a large number of abnormal white blood cells. In rarer cases of AML, abnormal red blood cells or platelet-producing cells are produced. With time, these cells can begin to build up, leaving less room for normal white blood cells, red blood cells and platelets. As a result, the immune system becomes weakened and the body is unable to fight infections and blood clotting is impaired. Reduced amounts of red blood cells is called anemia and decreased platelets is referred to as thrombocytopenia.

AML develops in the bone marrow, but the leukemic cells typically spread quickly into the blood. Eventually, they can spread farther into the lymph nodes, liver, spleen, brain, spinal cord and testicles. With successful treatment, remissions are frequent and some patients are cured.

The exact cause of AML has not been identified. However, researchers have gained a greater understanding of how specific changes in DNA can cause cells to develop into leukemia. A number of risk factors have also been identified, including smoking and exposure to very high levels of radiation. 

Symptoms of AML vary depending on where it has spread in the body. General signs and symptoms include weight loss, fever, loss of appetite, fatigue and weakness. Infections, pallor, bleeding or easy bruising are also common signs.

AML may be first detected in routine blood tests. However, additional tests, including bone marrow tests, are typically needed to verify the diagnosis. The treatment and prognosis for AML depends on the subtype of the disease, as well as certain additional factors including the patient’s age. It may include chemotherapy, radiation therapy, and bone marrow/stem cell transplantation. AML patients often receive a combination of these therapies for treatment of the disease.

The American Cancer Society (ACS) predicts that in 2007 there will be about 13,500 new cases of AML in the United States. The disease is more common in older adults, with the average age being 65 years. The prognosis is worse for older patients, with a five-year survival rate for people over age 65 at about 4 percent. The overall AML survival rate in adults under age 65 is approximately 33 percent. However, other factors, including the patient’s general health, can affect the prognosis.

About acute myeloid leukemia

Acute myeloid leukemia (AML) is a type of leukemia, or cancer of the body’s blood-forming cells. Also known as acute myelogenous leukemia, it affects the body’s blood making system which includes bone marrow and the lymphatic system.  Although the abnormal cells of AML initially develop in the bone marrow, they typically spread quickly into the blood and eventually they may spread further to other organs.

Bone marrow is the soft, inner component of bones. It is composed of blood-forming cells, fat cells, and supportive tissues. All forms of blood cells are produced in the bone marrow from a cell called the stem cell. Blood cells produced from stem cells in the bone marrow include:

  • White blood cells (cells that are involved in the immune system and fight infection). The three main types of white blood cell include:
    • Granulocytes (neutrophils, basophils, and eosinophils)
    • Monocytes
    • Lymphocytes
  • Red blood cells (cells that carry oxygen to tissues all over the body).
  • Platelets (cells that help develop blood clots and control bleeding).

In AML, the stem cells that normally develop into cells called myeloblasts fail to mature into healthy white blood cells. Because they are defective, the cells are unable to defend the body from disease. Although the condition occurs rarely in people with AML, stem cells can develop into a large number of abnormal red blood cells (erythroblasts) or platelet-producing cells (megakaryoblasts). These produce uncommon forms of AML.

As the leukemia progresses, the levels of abnormal cells gradually build up in the blood and bone marrow, crowding out normal white blood cells, red blood cells and platelets. As a result, production of normal white blood cells decrease, and the body’s ability to fight infection is impaired. In addition, the decrease in production of red blood cells and platelets results in anemia and bleeding disorders.

There are many different types and subtypes of leukemia. In general, the disease is first classified according to whether the majority of abnormal cells are mature or immature.  Leukemia developing from immature cells is classified as acute while leukemia developing from more mature cells is classified as chronic. The second classification is based on the exact type of cell from which the leukemia developed. Leukemia can develop in two forms of blood cells, lymphocytes andmyeloid cells

AML is classified as a myeloid leukemia because it develops from myeloid cells. These are cells that eventually develop into red blood cells, white blood cells, and platelet-producing cells (megakaryocytes). It is classified as acute because it develops from immature cells known as blast cells. Acute forms of leukemia develop quickly and, without proper treatment, are fatal within a few weeks to a few months.

Another form of myeloid leukemia is chronic myeloid leukemia. Although this type of leukemia also develops from myeloid cells, it differs from AML because it develops from more mature cells (chronic).

According to the American Cancer Society (ACS), more than 44,000 new cases of leukemia will be diagnosed in the United States in 2007. Of these new cases, about 13,500 will be AML. It is the most common form of leukemia, and more than 90 percent of AML cases occur in adults, with the average age being over 65. In addition, the disease is more common in men than in women.

Risk factors and causes of AML

The exact cause of acute myeloid leukemia (AML) has not been identified. However, researchers have gained a greater understanding of how specific changes in DNA can cause bone marrow stem cells to develop into leukemia.

DNA is the genetic material that houses instructions for all of the body’s chemical processes. Some forms of cancer are caused by DNA mutations that “turn on” oncogenes (genes that speed up cell division) or “turn off” tumor suppressor genes (genes that slow down cell division or cause cells to die at the right time). In people with leukemia, these mutations are normally acquired after birth. The mutations may occur from exposure to radiation or cancer-causing chemicals, but many times the mutations occur for no apparent reason.

In addition, researchers have identified a number of factors that may make a person more likely to develop AML. These risk factors include:

  • Smoking. Tobacco smoke contains cancer-causing substances that are absorbed by the lungs and spread through the bloodstream to numerous parts of the body.  It is especially risky for older adults, as smoking doubles the chances of developing AML in patients over 60.
  • Chemotherapy. Patients treated for other cancers with certain chemotherapy drugs are at an increased risk of developing leukemia (secondary leukemia). These drugs are part of a class of drugs called alkylating agents and do not include all chemotherapy drugs.

    Recent studies have indicated that patients who receive higher-than-standard doses of two chemotherapy drugs (epirubicin and cyclophosphamide) have an increased risk of secondary leukemias, such as AML.

    AML is the most common form of secondary leukemia and usually occurs within 9 years after treatment. It most often develops after treatment for Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and childhood acute lymphocytic leukemia (ALL). The risk is even greater if treatment uses both chemotherapy and radiation therapy. 
  • Exposure to very high levels of radiation. Patients who have received radiation therapy as treatment for other forms of cancer have an increased risk of developing AML later in life. In addition, people exposed to radiation from atomic blasts (such as those in Japan during World War II) and nuclear accidents have an increased risk of developing AML.
  • Benzene. Benzene is a colorless, flammable liquid used primarily as a solvent and a gasoline additive. It is also a component of cigarette smoke. Long-term exposure to the chemical can increase a person’s risk of developing AML.
  • Gender. AML is more common in males than in females.
  • Age. The disease most often occurs in older adults, and a person’s risk of developing AML increases with age. The average age of a person with AML is 65, and it rarely occurs before the age of 40. According to the American Cancer Society (ACS), a 50 year-old person’s chance of developing AML is 1 in 25,000. For a 70 year old person, the odds are 1 in 7,000.
  • Obesity. Studies have indicated that individuals who are significantly overweight have an increased risk of developing myeloid leukemia. The incidence of myeloid leukemia was roughly five times higher among overweight and obese individuals than those with normal or low weight in a large study reported by the National Cancer Institute. Scientists believe that obesity may alter immune function. In addition, excess fat around the waist area may be related to chronic high levels of insulin and hormones that stimulate cell growth and inhibit cell death.
  • Other blood disorders. People with certain blood disorders have an increased risk of developing AML. These disorders include:
    • Myelodysplastic syndromes. Myelodysplastic syndromes (MDS) are conditions caused by abnormally developing cells of the bone marrow. Some physicians consider these syndromes pre-leukemia as approximately 30 percent of MDS cases evolve into AML.
    • Polycythemia vera (an abnormal increase in the production of red blood cells).
    • Thrombocythemia (an abnormal increase in the production of platelets).
  • Genetic syndromes. People with certain genetic syndromes, such as Down syndrome, have an increased risk of developing AML.

Although acute myeloid leukemia may be associated with these risk factors, most patients with the disease have no known risk factors.

Signs and symptoms of acute myeloid leukemia

Acute myeloid leukemia (AML) can cause a variety of signs and symptoms. In general, patients may experience an overall decline in well-being, including:

  • Weight loss
  • Fever
  • Loss of appetite
  • Weakness and fatigue

Signs and symptoms of AML may develop from the reduction of normal red blood cells, white blood cells and platelets caused by the disease. These blood abnormalities may cause the following conditions and symptoms:

  • Anemia.An abnormally low amount of red blood cells. It can trigger a variety of signs and symptoms including pallor, fatigue and shortness of breath.
  • Infection. Decreased levels of normal white blood cells weaken the immune system and cause a greater risk for infection. The infection may or may not be accompanied by a fever.
  • Thrombocytopenia. An abnormally low amount of platelets. This condition result in excessive bleeding or bruising.
  • Enlargement of spleen or liver. This can cause a feeling of fullness between the ribs or swelling of the abdomen.
  • Bone and joint pain. Caused by the spread of the disease to the bone.
  • Leukemia cutis and chloromas. Painless blue, blue–green or purple colored lumps that may appear in the neck, underarm, stomach or eye areas.
  • Rashes.  Spread of these malignancies to the skin may cause small spots that look like an ordinary rash. Capillary bleeding due to low platelets may also mimic a rash.

Early symptoms of AML may be overlooked because they can resemble symptoms of more common illnesses, such as influenza. Patients are encouraged to contact their physician when they experience any symptom of AML. The earlier the disease is diagnosed, the earlier treatment may begin and the better the prognosis.

Diagnosis methods for acute myeloid leukemia

When physicians suspect that a patient may have acute myeloid leukemia (AML), they first will obtain a detailed medical history and perform a complete physical examination. During the physical examination, the physician will examine the lymph nodes, spleen and liver for swelling.

Next, a variety of tests may be ordered to diagnose, classify, and monitor the leukemia.  Samples of cells from the patient’s blood and bone marrow will be examined to verify the diagnosis. Additional tissue and cell samples may also be needed to guide treatment.

Common tests that can help diagnose AML include:

  • Complete blood count and blood smear. A complete blood count (CBC) is a blood test that measures the number of red blood cells, white blood cells and platelets in a sample of blood. A CBC also measures the amount of hemoglobin in the red blood cells and a number of other factors. A blood smear is the examination of cells under a microscope. Changes in the numbers of different blood cell types and the appearance of the cells can suggest leukemia. Patients with AML usually have too many white blood cells and many of the cells will be blasts, an immature blood-forming cell usually found only in the bone marrow. Many patients may have too few red blood cells and platelets as well.
  • Bone marrow aspiration and biopsy. Although other tests may suggest AML, the diagnosis usually cannot be verified without examining a sample of bone marrow cells. A bone marrow aspiration involves using a needle to collect a small sample of liquid bone marrow. A bone marrow biopsy uses a larger needle to remove a core of bone marrow.  Usually performed at the same time, these procedures may be ordered to determine if leukemia is present or to monitor treatment.
  • Blood chemistry tests. These tests measure the level of specific chemicals in the blood. They are used to monitor changes in organ function caused by the leukemia or the treatment with certain chemotherapy drugs. The tests may be ordered to determine whether treatment is required to correct abnormalities.

Additional tests include laboratory tests to diagnose and classify the leukemia. These include:

  • Routine microscopic exam. All samples (bone marrow, lymph node tissue, blood and cerebrospinal fluid) are studied under a microscope by a pathologist. A number of characteristics, including the size, shape and maturity of the cells are noted in order to classify the cancer cells into specific types.  The test also may be ordered to determine if a patient is in remission.

    Blasts are the most immature type of cell. The amount of cells in the bone marrow that are blasts will be determined for diagnosis of AML. Blasts may contain a chromosome change that is specific for a type of AML. Following treatment, a patient must have a blast percentage of 5 percent or less to be considered in remission.
  • Flow cytometry and immunophenotyping. This procedure detects certain molecules on the surface of leukemia cells. This is a very accurate test for determining the exact type of leukemia present in a patient.
  • Cytogenetics. This test uses a microscope to evaluate the chromosomal characteristics of cells. It may be ordered to determine if the cells have too many chromosomes, or if the chromosomes have any abnormalities. The testing usually takes up to 3 weeks because the leukemia cells must grow in a laboratory before the chromosomes can be analyzed. Certain chromosomal abnormalities have been identified in AML cells and their presence or absence may help in predicting a patient’s prognosis.
  • Molecular genetic studies. These tests are more sensitive in examining leukemia cell DNA for precise abnormalities.  Molecular genetic studies are useful in classifying AML because many of its subtypes have translocations that are too small to be detected with a microscope. Information about the translocations can be used to predict the patient’s response to treatment and detect remaining cancer cells following treatment. 

AML rarely forms visible tumors. For that reason, imaging tests have limited value. If imaging tests are performed on patients with AML, they are usually conducted to diagnose infections or other leukemia-related problems. Imaging tests that may be ordered include chest x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI), gallium scan, bone scan and ultrasound. The imaging tests may be used to detect enlarged organs or lymph nodes, large collections of leukemia cells and sites of infection.

Treatment options for acute myeloid leukemia

Treatment for acute myeloid leukemia (AML) is usually coordinated by a cancer care team, headed by a hematologist or medical oncologist.

There are a variety of methods used to treat AML. The exact treatment method chosen for each patient depends on the subtype of the leukemia as well as certain prognostic factors including the patient’s age, white count and general medical status.

Patients with AML usually are treated immediately and aggressively in order to destroy the leukemia cells in the blood and bone marrow and put the leukemia in remission. AML treatment is divided into two phases and the first is known as remission induction therapy. After the signs and symptoms of the disease disappear, additional therapy may be given to destroy any undetected leukemia cells and prevent a relapse. This is known as postremission therapy or consolidation therapy.

Because leukemia is a blood disorder and does not form tumors, surgery is not a form of treatment. Common treatment methods for AML include:

  • Chemotherapy. Uses powerful anti-cancer drugs to destroy cancer cells. When used to treat AML, a combination of drugs may be used. Chemotherapy is usually the main treatment method for AML. A plastic tube called a venous access device may be inserted into a patient’s vein for chemotherapy. This provides easier access for drug delivery and allows blood samples to be removed without repeated needle sticks.
  • Radiation therapy. Uses high-energy rays to destroy cancer cells and shrink tumors. It may be ordered to treat leukemia that has spread to the brain, spinal fluid or testicles. Radiation therapy may be ordered before a patient undergoes a bone marrow or peripheral blood stem cell transplantation. On rare occasions, radiation treatment may be ordered as an emergency treatment to reduce the size of a mass pressing on the trachea.
  • Monoclonal antibodies. Proteins made in a laboratory that can be designed to attach to certain molecules on the surface of AML cells. When injected into a person with leukemia, the antibodies destroy the cancer cells. Monoclonal antibodies may be bound with a radioisotope or cell toxin to increase effectiveness. It may be used to treat older AML patients who have relapsed after initial chemotherapy and may not be able to tolerate further chemotherapy. Research continues into the use of monoclonal antibodies as treatment for leukemia patients.
  • Bone marrow/stem cell transplantation. Transplantation of bone marrow cells or peripheral blood stem cells. The stem cells may come from a matched donor or from the patients themselves. This is not a direct treatment for cancer, but helps the body to tolerate higher levels of chemotherapy, radiation therapy or a combination of both. In addition to destroying cancer cells, high dose therapies also destroy normal blood cells in the bone marrow. Patients who undergo transplantation receive an infusion of healthy stem cells through a vein after high-dose therapies. As a result of the infusion, new blood cells begin to develop from the transplanted cells. This procedure is complex and cannot be used with all patients.

Treatment of the M3 subtype of AML (acute promyelocytic leukemia [APL]) differs from the treatment of other subtypes because patients with APL may develop serious blood-clotting or bleeding problems. Anticoagulants (medicines that thin the blood) may be prescribed to prevent or treat these disorders. Other treatment options include transfusions of platelets or other blood products. Overall, induction therapy is successful in approximately 65 percent of all AML patients.

There are a number of terms that may be used to describe the status of AML following treatment. These terms include:

  • Relapse (recurrence). The return of leukemia after the initial treatment is known as relapse. A patient with more than five percent blast cells present in the bone marrow may be classified as being in relapse.
  • Remission. Following treatment AML may be classified as being in remission when:
    • The complete blood count is normal.
    • There are less than 5 percent blast cells in the bone marrow.
    • There are no signs or symptoms of the disease detected anywhere in the body.
  • Active disease. In a patient who is newly diagnosed or in relapse, AML will be classified as active disease.
  • Minimal residual disease. This term is used to describe a case of AML when there is molecular evidence that cancer cells remain in the bone marrow, but there are not enough of the cells to be detected by routine examination under a microscope.

Following treatment, patients typically require regular visits to their physician for several years. Frequent checkups enable the physician to detect any changes in health and provide immediate treatment. Checkups may include a physical examination, x-rays, blood tests, and other lab tests. In most cases, a CBC and often a repeat bone marrow are included to monitor the disease.

Patients are encouraged to report the development of any new symptoms to their physician. They may be a sign of recurrent AML or side effects of treatment. The disease can return in the blood, bone marrow, or other parts of the body. It is unusual for AML to return when there are no signs of the disease five years after treatment.

According to the American Cancer Society (ACS), the overall AML survival rate in adults under age 65 is approximately 33 percent. For patients over age 65, the 5-year survival rate is about 4 percent. However, it is less likely that patients over 65 will receive intensive anti-leukemia therapy because of concurrent serious medical conditions or patient choices.

Prevention methods for acute myeloid leukemia

There are no specific ways to prevent acute myeloid leukemia (AML). Avoidance of controllable risk factors offers the only possibility of preventing the disease. Smoking is the biggest controllable risk factor for AML. Individuals who do not use tobacco have the best chance of preventing AML, as well as other smoking-related cancers.  

Avoiding the chemical benzene can also reduce a person’s risk of developing the disease.  However, many experts agree that occupational and environmental chemicals are responsible for only a small number of leukemia cases. 

Although chemotherapy and radiation therapy for other cancers can cause secondary AML, the lifesaving benefits of these treatments should be carefully weighed against the small risk of developing leukemia later in life.

Ongoing research regarding AML

There is a great deal of research being conducted in the area of acute myeloid leukemia (AML) including clinical trials and scientific studies. Areas of research for AML include:

  • Genetics. Researchers are studying how changes in a person’s DNA can cause normal bone marrow cells to develop into abnormal leukemia cells. Studies of DNA changes in AML have yielded a more sensitive test for detecting leukemia cells after a patient has undergone treatment. The test, known as polymerase chain reaction (PCR) test can identify acute leukemia cells based on DNA changes, such as translocations. A PCR test can be beneficial in determining the success of treatment in destroying AML cells. It can also help predict whether relapse is likely to occur.
  • Stem cell transplantation. Scientists continue to examine ways to increase the effectiveness of stem cell transplantation and methods to reduce the complications. Studies continue to focus on which individuals most benefit from stem cell transplants.
  • Chemotherapy. New chemotherapy drugs are being studied for treatment of the disease. Other studies have focused on ways to prevent leukemia cells from becoming resistant to chemotherapy, and determining the most effective combination of drugs. Researchers are also trying to determine whether patients with a poor prognosis and chromosomal pattern benefit from intensive chemotherapy.  
  • Targeted therapies. Researchers are developing new targeted drugs that specifically attack some of the genetic abnormalities seen in patients with AML.  A group of new drugs called FLT3 inhibitors appear to block mutation of chromosomes. These drugs are only available in clinical trials but they have been effective, particularly when they paired with chemotherapy. Some trials are examining the effectiveness of combined targeted therapies that block multiple molecular pathways. Research has also targeted other gene mutations found in the c-KIT gene in some cases of AML.
  • Gene-expression profiling. This experimental technique is being used with several types of cancer. The testing analyzes the pattern of genes found in cancer cells and helps distinguish certain types of cancer. In AML, the profiling is being used to classify the disease into subtypes and risk categories. The profiling also helps physicians plan specific treatment and evaluate the patient’s prognosis.

Classifying AML

Most types of cancer are classified by a process known as staging. Staging assigns numbered stages to cancers based on tumor size and how far the cancer spreads from the original site. Leukemia, however, is not staged because it involves all the bone marrow in the body. In many cases, it spreads to other organs through the bloodstream.

Diagnostic tests focus on establishing the type and subtype of leukemia. This information is then used to determine the prognosis and predict which treatments will be most effective. Subtypes of AML respond to treatment differently and their prognoses vary.

The classification of these subtypes is based on a classification system known as the French-American-British (FAB) Classification of AML. Based on the type of cell from which the leukemia developed, this system consists of eight subtypes including:

SubtypeApproximate percent of cases in adultsPrognosis
M0 (undifferentiated AML)5%Poor
M1 (myeloblastic leukemia with minimal maturation)15%Average
M2 (myeloblastic leukemia with maturation)25%Good
M3 (promyelocytic leukemia)10%Excellent
M4 (myelomonocytic leukemia)20%Average
M4 eos (myelomonocytic leukemia with eosinophilia)5%Good
M5 (monocytic leukemia)10%Average
M6 (erythroid leukemia)5%Poor
M7 (megakaryoblastic leukemia)5%Poor

In addition to these subtypes, certain prognostic factors have been identified to help a physician determine if a patient requires more or less treatment. Adult AML prognostic factors include:

  • Age. Patients over the age of 60 have a worse prognosis than younger patients.

  • White blood cell count. Patients with a white blood cell count above 100,000 have a worse prognosis.

  • Having a prior preleukemic condition. Patients who have a prior preleukemic condition (e.g., myelodysplastic syndrome) have a worse prognosis.  

  • Having secondary AML. Patients who develop AML after receiving chemotherapy or radiation therapy for another cancer have a worse prognosis.

  • Having an unfavorable chromosome abnormality. Analysis of abnormalities in the chromosomes (cytogenics) may be the best predictor of a patient’s response to treatment.

    • Whether the AML has spread to the brain or spinal cord. Patients with AML that has infiltrated the brain or spinal cord have a worse prognosis.

    • Whether the AML has been treated previously.Patients who have been treated for AML have a poorer prognosis.

 Questions for your doctor about AML

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about acute myeloid leukemia (AML):

  1. How does AML differ from other forms of leukemia?
  2. What tests will I be given to diagnose AML?
  3. How will the bone marrow aspiration and biopsy be performed?
  4. When and from whom will I receive the test results?
  5. What type of AML do I have?
  6. What is my prognosis for this type of AML?
  7. What are my treatment options?
  8. What are the risks associated with these treatments?
  9. If I need a bone marrow transplant, can I use my own bone marrow?
  10. If not, how will a matching donor be located?
  11. How does a patient know if he or she is in remission?
  12. What are the chances my AML will return?
  13. Does AML increase my risk of other cancers?
  14. Am I am candidate for a clinical trial?
  15. How will my condition be monitored following treatment?
  16. If I have AML, will my children be more at risk for developing the disease?
  17. Can you recommend a support group?
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