Acute myeloid leukemia (AML) is a cancer affecting white blood cells. AML may sometimes be called acute myelogenous leukemia, acute myelocytic leukemia, or acute nonlymphocytic leukemia. Unlike chronic leukemia, acute leukemia develops quickly and generally requires immediate treatment. AML occurs in people of all ages but is most common in adults older than 65.
AML is a disorder of the process that normally produces neutrophils, a type of white blood cell. Neutrophils fight infections caused by bacteria. The production of mature neutrophils usually is highly regulated. For example, the body rapidly makes more neutrophils during an infection and returns to a regular level of production when the infection is controlled. Mature neutrophils develop from immature white cells in a process called differentiation.
In AML, acquired mutations (damage to the genetic material or DNA) in the blood-forming cells disrupt the normal process of differentiation, resulting in the accumulation of large numbers of immature (undeveloped) cells called myeloblasts or blasts. Blasts cannot function like fully developed, healthy blood cells. The large number of blasts also reduces the production of healthy red blood cells and platelets. Therefore, patients with AML are usually anemic (because they do not have enough red blood cells), susceptible to infection (because they do not have enough mature neutrophils), and bruise or bleed easily (because of a low level of platelets).
AML is usually found in the blood and bone marrow (the spongy, red tissue in the inner part of the large bones), but it can sometimes also invade other sites, such as the brain, skin, and gingiva (gums). Occasionally, AML cells can form a solid tumor called a myeloid sarcoma or chloroma that may be located nearly anywhere in the body.
In 2008, an estimated 13,290 people of all ages (7,200 males and 6,090 females) in the United States will be diagnosed with AML. Of these, 12,700 will be adults. AML is the second most common type of leukemia diagnosed in adults. An estimated 8,820 deaths (5,100 males and 3,720 females) will occur in 2008.
Although AML is a serious disease, it is treatable with chemotherapy. The five-year relative survival rate (percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) of patients with AML is 21%. It is important to note that survival depends on several factors, including biologic features of the disease.
Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with AML. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.
Statistics adapted from the American Cancer Society's publication, Cancer Facts and Figures 2008.
A risk factor is anything that increases a person’s chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.
Although the cause of AML is not known, several factors are associated with an increased risk of the disease. The following factors may raise a person’s risk of developing AML:
Age. AML is more common in older adults, and the median age at diagnosis is 65.
Smoking. An estimated 20% of AML cases may be linked to exposure to tobacco smoke, probably in association with other causes as well.
Genetic disorders. AML occurs more frequently in people with inherited disorders such as Down syndrome, ataxia telangiectasia, Li-Fraumeni syndrome, Klinefelter’s syndrome, Fanconi’s anemia, Wiskott-Aldrich syndrome, and Bloom’s syndrome.
High doses of radiation. People who have been exposed to high levels of radiation, such as long-term survivors of atomic bombs, may be more susceptible to AML.
Previous cancer treatment. Patients who have received chemotherapy and/or radiation therapy for other types of cancer, such as breast cancer, ovarian cancer, and lymphoma, have a higher risk of AML in the years following such treatment.
With the exception of prolonged contact with benzene products, exposure to industrial solvents and hair dyes has not been proven to increase a person’s risk of AML.
People with AML may experience the following symptoms. Sometimes, people with AML do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your doctor.
Fatigue
Weakness
Easy bruising or bleeding
Weight loss
Fever
Bone or abdominal pain
Difficulty breathing; dyspnea (shortness of breath)
Doctors use many tests to diagnose cancer and determine if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:
Age and medical condition
The type of cancer suspected
Severity of symptoms
Previous test results
The following tests may be used to diagnose AML:
Blood tests. To diagnose AML, a doctor will do blood tests to count the number of white blood cells and to see if they look abnormal under the microscope. Special tests called flow cytometry (immunophenotyping) and cytochemistry are sometimes used to distinguish AML from other types of leukemia and to determine the exact subtype of AML. Chromosome studies called cytogenetics are used to identify genetic changes in the AML blasts, and these changes often help doctors decide the best course of treatment.
Genetic testing. An increasing number of genetic mutations in the AML cells are being identified that can help determine prognosis (chance of recovery), and these molecular analyses are now being done more often at the time of diagnosis.
Bone marrow biopsy. In a bone marrow biopsy, a doctor takes a sample of marrow, usually from the back of the hipbone, with a needle. The patient is given medication to numb the area beforehand. The cells from the marrow, along with the cells from the blood, are analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease).
Lumbar puncture (spinal tap). A lumbar puncture is a procedure in which a doctor takes a sample of cerebral spinal fluid (CSF) to look for cancer cells, blood, or tumor markers (substances found in higher than normal amounts in the blood, urine, or body tissues of people with certain types of cancer). CSF is the fluid that flows around the brain and the spinal cord. Doctors generally give an anesthetic to numb the lower back before the procedure. The CSF is then examined under the microscope for the presence of AML cells.
Imaging tests. Acomputed tomography (CT or CAT) scan (test that creates a three-dimensional picture of the inside of the body) or magnetic resonance imaging (MRI, test that uses magnetic fields, not x-rays, to produce detailed images of the body) may be used to learn more about the cause of symptoms or to help diagnose infections in patients with AML. They are not regularly used for staging of AML since the disease is known to have spread throughout the bone marrow and blood at the time of diagnosis. The use of these tests for evaluating the AML depends on particular clinical findings in individual patients.
There is a variety of subtypes of AML. Although all subtypes cause decreases in normal blood counts, different types of AML are associated with specific symptoms and problems and can have widely different results after treatment.
Morphology
AML is initially defined according to its morphology (the appearance of the cancerous cells under the microscope). The classification of AML is named according to the type of normal, immature white blood cell it most closely resembles.
Most patients with AML are classified as having myeloblastic leukemia, which means the cancer is in the cells that normally produce neutrophils. Other patients have a type of AML called monocytic. In monocytic leukemia, the cells resemble other white blood cells called monocytes. Mixtures of myeloblastic and monocytic leukemia can occur.
Sometimes the AML seems to come from cells that produce red blood cells (erythroid) or platelets (megakaryocytic). Promyelocytic leukemia is a unique subtype of AML where the cancer cell stops maturing when the cell is at a stage called the promyelocyte or progranulocyte. Flow cytometry is a test that can detect the presence of particular proteins on the surface of abnormal cells and is sometimes useful in distinguishing among these subtypes.
The classification system from the World Health Organization (WHO) includes:
AML with recurrent genetic abnormalities (that is, with specific chromosomal changes)
AML with multilineage dysplasia (abnormalities in the appearance of other blood cells)
AML with myelodysplastic syndrome, related to therapy
AML that is not otherwise categorized
The French-American-British (FAB) classification is an older system for describing AML morphology, but it is still commonly used and is listed below for reference.
M0: Myeloblastic without differentiation
M1: Myeloblastic without maturation
M2: Myeloblastic with maturation
M3: Promyelocytic
M4: Myelomonocytic
M5a: Monocytic without differentiation (monoblastic)
M5b: Monocytic with differentiation
M6: Erythroleukemic
M7: Megakaryocytic
Cytogenetics
AML is also classified according to the cytogenetic (chromosome) changes found in the leukemia cells. Sometimes the doctor can find these changes visually by examining the chromosomes under the microscope, while other changes can be detected only with sophisticated molecular tests that can identify very small changes in the DNA.
Certain chromosomal changes are closely matched with particular morphologic subtypes of AML. More importantly, in many cases the chromosomal changes are highly predictive of the results of treatment and often influence the choice among different treatment approaches. These changes are commonly grouped according to the likelihood that the subtype will respond to treatment. (Note: all chromosomes are numbered from one to 22; sex chromosomes are called “X” or “Y.” The letters “p” and “q” refer to the “arms” or specific areas of the chromosome.)
Some of the most common chromosomal changes are grouped as follows:
Favorable. Chromosomal changes associated with a good result after treatment include abnormalities of chromosome 16 at bands p13 and q22, a translocation (exchange of genetic material) between chromosomes 8 and 21, and a translocation between chromosomes 15 and 17 (found in progranulocytic leukemia).
Intermediate. Findings suggestive of a less favorable prognosis include normal chromosomes (no abnormality detected) and a translocation between chromosomes 9 and 11.
Unfavorable. Examples of chromosomal changes predictive of unfavorable outcomes and low cure rates include extra copies of chromosomes 8 or 13, deletion of all or part of chromosomes 5 or 7, complex abnormalities involving many chromosomes, and abnormalities of chromosome 3 at band q26.
In general, the more favorable changes occur in younger patients, while the unfavorable changes are more common in patients older than 60. In each of these groups, there is still a wide range of how the cancer responds to treatment, with average expected rates of successful AML treatment ranging from 50% to 60% in the favorable group to less than 10% in the unfavorable group. Other factors, including the patient’s age and the level of the white blood cell count, also influence how well treatment works. It is not possible to predict exactly the likelihood of successful treatment in an individual person with AML.
Recurrent. Recurrent AML is cancer that comes back after treatment.
The treatment of AML depends on the subtype, morphology, and cytogenetics of AML (see Subtypes) and the patient’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.
The most successful treatment for AML depends on the results of the first treatment, so it is important to undergo the initial treatment at a center with expertise in AML.
This section outlines treatments that are the standard of care (the best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials as a treatment option when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials section.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. The drugs travel through the bloodstream to cancer cells throughout the body. Chemotherapy is the primary treatment for AML. Chemotherapy may be given by mouth, injected into a vein, or injected into the CSF. Several drugs are used to treat AML.
Chemotherapy for AML can be divided into three phases: remission induction, post-remission consolidation, and maintenance. Maintenance refers to the prolonged use of chemotherapy for patients in remission and is not commonly used in AML.
Induction. This stage of therapy refers to the initial period of treatment after the diagnosis is made. The combination of cytarabine (Cytosar-U, Tarabine PFS) given over seven days and an anthracycline drug (daunorubicin [Cerubidine, Rubidomycin] or idarubicin [Idamycin]) given for three days is used most often. In addition to killing leukemia cells, these drugs also destroy healthy cells, increasing the risk of infection and bleeding (see below). Most patients require hospitalization for three to five weeks during this period of induction therapy. Sometimes, two courses of therapy are needed to achieve a complete remission, which is the goal of this initial phase.
Complete remission(CR). A CR means that the blood counts have returned to normal, meaning leukemia is not visible when a marrow sample is examined under the microscope, and the signs and symptoms related to the AML are gone. Approximately 75% of younger adults with AML and about 50% of patients older than 50 achieve a CR after treatment.
Consolidation or intensification. This stage of chemotherapy refers to the use of a variety of different drugs that are designed to kill remaining AML cells after successful induction. It is known that the AML will usually recur if no further therapy is given after a CR. Administration of two to four courses of high-dose cytarabine given at monthly intervals is commonly used for younger adults in remission, while a number of different regimens are used for older patients. Although the chemotherapy is usually given in the hospital, most of the recovery time is spent as an outpatient.
For some patients, stem cell transplantation (see below) is recommended as a substitute for consolidation therapy.
The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Drug Information Resources, which provides links to searchable drug databases.
Acute promyelocytic leukemia (APL) treatment
The treatment of the APL subtype of AML is somewhat different. This subtype is remarkably sensitive to the effects of all-trans retinoic acid (ATRA), a derivative of vitamin A, which is given by mouth. The combination of ATRA and chemotherapy with idarubicin or daunorubicin produces a very high rate of CR.
Bleeding is a common complication of APL, and patients with this subtype of AML often require large numbers of platelet and blood transfusions during the initial stages of their treatment. In contrast to other subtypes of AML where maintenance therapy is not used, patients with APL benefit from the long-term (one to two years) use of ATRA. Arsenic trioxide (Trisenox) is effective when given intravenously (through a vein) for the treatment of recurrent APL.
Side effects of chemotherapy
The chemotherapy given to treat AML attacks rapidly dividing cells, including those in normal tissues, such as the hair, lining of the mouth, intestines, and bone marrow. Patients with AML receiving chemotherapy may lose their hair, develop mouth sores, or have nausea and vomiting. Hair will regrow after treatment is completed, and effective antiemetic drugs help prevent nausea and vomiting.
Chemotherapy may also affect the patient’s future fertility (ability to conceive a child or maintain a pregnancy). Because of the effect on the bone marrow, the chemotherapy used in AML will temporarily lower the body’s resistance to infection, lead to increased bruising and bleeding, and cause fatigue. Patients with AML will receive a variety of antibiotics to prevent and treat infections and will require transfusions of red blood cells and platelets throughout their chemotherapy treatments.
Radiation therapy
Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells.The most common type of radiation therapy is called external-beam radiation therapy, which is radiation given from a machine outside the body. Because AML is found throughout the body in the blood, radiation therapy is generally used only when the cancer has spread to the brain or to shrink chloromas (localized tissue masses). Side effects from radiation therapy may include tiredness, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.
A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because blood stem cells are typically what is being transplanted, not the actual bone marrow tissue.
There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO).
In an ALLO transplant, stem cells are obtained from a donor whose tissue matches the patient’s on a genetic level; this testing is called HLA-typing. Most often, a patient’s brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; matches can be made by searching a computer registry. In addition, stem cells derived from umbilical cord blood are sometimes considered if family donors are not available.
In an AUTO transplant, the patient’s own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until they are needed, usually after the high-dose treatment (explained below) is completed.
In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. This also destroys the patient’s bone marrow tissue and suppresses the patient’s immune system so that, in an ALLO transplant, the donor cells are not rejected by the body. After the high-dose treatment is given, blood stem cells are infused into the patient’s vein to replace the bone marrow and restore normal blood counts from donor cells. Sometimes, ALLO transplants can also be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. (These transplants, sometimes termed “mini-transplants” or “reduced intensity transplants” have less immediate side effects, allowing the procedure to be used for older patients.)
Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of cancer, results of any previous treatment, and patient’s age and general health.
For both ALLO and AUTO transplant types, the replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in 10 days to three weeks. Destroying the patient’s own marrow reduces the body’s natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.
In an ALLO transplant, another major risk is that the donor’s cells will recognize the patient’s body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit, in that the donor cells can recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventative drugs.
In an AUTO transplant, there is little risk of GVHD because the replacement stem cells are the patient’s own cells. However, there is a risk in an autologous transplant that some of the cells that are put back into the patient could still be cancerous.
If leukemia is still obviously present after initial treatment, the disease is referred to as refractory AML. Patients with refractory disease may be offered new drugs being tested in clinical trials. Patients should also be considered for ALLO transplant as part of their treatment program.
The treatment for recurrent AML often depends on the length of the initial remission. If ALL comes back after a long remission, it may respond again to the original treatment. If the remission was short, then other drugs are used, often in the form of new drugs being tested in clinical trials. An ALLO stem cell transplant is often offered to patients whose leukemia has come back after initial treatment. However, the best treatment after a remission is not known, and many drugs and other approaches are being evaluated in clinical trials.
Doctors and scientists are always looking for better ways to treat patients with AML. A clinical trial is a way to test a new treatment to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.
Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that finding new drugs and other therapies is the only way to make progress in treating AML. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with AML.
To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.
Cancer and its treatment can cause a variety of side effects. However, doctors have made major strides in recent years in reducing pain, nausea and vomiting, and other physical side effects of cancer treatments. Many treatments used today are less intensive but as effective as treatments used in the past. Doctors also have many ways to provide relief to patients when such side effects do occur.
Fear of treatment side effects is common after a diagnosis of cancer, but it may be helpful to know that preventing and controlling side effects is a major focus of your health-care team. Before treatment begins, talk with your doctor about possible side effects of the specific treatments you will be receiving. The specific side effects that can occur depend on a variety of factors, including the type of cancer, its location, the individual treatment plan (including the length and dosage of treatment), and the person’s overall health.
Ask your doctor which side effects are most likely to happen (and which are not), when side effects are likely to occur, and how they will be addressed by the health-care team if they do happen. Also, be sure to communicate with the doctor about side effects you experience during and after treatment. For more information on the most common side effects of cancer and different treatments, along with ways to prevent or control them, visit the section on Managing Side Effects, based on ASCO’s curriculum.
In addition to physical side effects, there may be psychosocial (emotional and social) effects as well. Learn more about the importance of addressing these needs in the section on Caring for the Whole Patient.
For more information on late effects or long-term side effects, please read the After Treatment section or talk with your doctor.
After treatment for AML ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years.
People in remission should receive regular follow-up examinations for several years to detect early evidence of recurrence or late effects (side effects that occur years after treatment) of chemotherapy.
People recovering from AML are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, not smoking, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about Healthy Living After Cancer.
AML research is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this current time. Always discuss all diagnostic and treatment options with your doctor.
Active research directed at increasing the understanding of the biology of AML is ongoing to improve its treatment, particularly for older patients. These projects include the following:
Research protocols evaluating the use of new drugs or existing drugs given in different doses and schedules
The evaluation of inhibitors of the products of specific mutations found in AML cells. For example, about 30% of patients with AML have mutations in a gene producing a protein called FLT3, which can increase the growth of AML cells. Compounds that inhibit FLT3 are being tested in clinical trials.
The evaluation of inhibitors of proteins found in AML cells that cause resistance to chemotherapy
The use of antibodies directed against the AML cells
The study of a variety of techniques to make stem cell transplantation safer, easier, and more effective
Most cancer centers are actively involved in clinical trials aimed at increasing the rate of cure from AML. The National Cancer Institute’s Clinical Trials Cooperative Group Program sponsors many of these studies. Please talk with your doctor about these ongoing clinical trials.
Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:
What is my diagnosis? What does it mean?
Can you explain my pathology report (laboratory test results) to me?
Do I need to start treatment right away?
What subtype of AML do I have?
Can you recommend a leukemia specialist?
Where is the best place for me to be treated?
What are my options for treatment?
What clinical trials are open to me?
What treatment do you recommend? Why?
What are the possible side effects of this treatment, both in the short term and the long term?
Will this treatment affect my fertility? If so, can you recommend a fertility specialist before treatment begins?
How likely is it that my AML will go into remission?
How will the treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
What follow-up tests will I need, and how often will I need them?
What support services are available to me? To my family?
American Society for Blood and Marrow Transplantation
85 W. Algonquin Rd., Ste. 550
Arlington Heights, IL 60005
Phone: 847-427-0224 www.asbmt.org
Blood and Marrow Transplant Information Network
2310 Skokie Valley Rd., Ste. 104
Highland Park, IL 60035
Toll Free: 888-597-7674
Phone: 847-433-3313 www.bmtinfonet.org
Leukemia Research Foundation
2520 Lake Ave., Ste. 202
Wilmette, IL 60091
Phone: 847-424-0600
Toll Free: 888-558-5385 www.leukemia-research.org
The Leukemia & Lymphoma Society
1311 Mamaroneck Ave., Ste. 130
White Plains, NY 10605
Toll Free: 800-955-4572 www.lls.org
National Bone Marrow Transplant Link
20411 West 12 Mile Rd., Ste. 108
Southfield, MI 48076
Toll Free: 800-LINK-BMT (800-546-5268)
Phone: 248-358-1886 www.nbmtlink.org
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