Acute myeloid leukemia (AML) is a cancer of the blood-forming tissue, within the bone marrow. AML may also be called acute nonlymphocytic leukemia or acute myelogenous leukemia. AML is the second most common form of leukemia in children, after acute lymphoblastic leukemia (ALL).
Bone marrow is spongy tissue found inside the bones and is the source of a person’s blood. Normal immature blood cells are called blasts. Blasts mature into one of three different types of blood cells:
White blood cells, which fight infection in the body
Red blood cells, which carry oxygen and other nutrients throughout the body
Platelets, which help the blood to clot
In AML, the bone marrow mistakenly produces large numbers of abnormal cancerous cells, also called blasts or myeloblasts because they look similar to normal immature blast cells. Instead of becoming the three types of normal mature blood cells, the cancerous cells divide rapidly out of control, are unable to mature and function as they were intended, and do not die easily. Eventually, these myeloblasts fill up the bone marrow, preventing normal cells from being produced, and then accumulate in the bloodstream. They can also invade the lymph nodes, brain, skin, liver, kidneys, ovaries (in girls), testicles (in boys), and other organs. AML cells occasionally form a solid mass, called a chloroma.
In 2007, about 695 children in the United States will be diagnosed with AML. AML is most common during the first two years of life and during the teenage years.
The five-year relative survival rate (the percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) for children with AML is about 60%.
Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer, 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.
Sources: National Cancer Institute, United Kingdom Medical Research Council Study MRC 12, and Children’s Oncology Group Study CCG-2961.
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.
Doctors and researchers don’t know what causes most childhood cancers. Evidence suggests that some cases of AML may be the result of certain genetic factors or environmental exposures; for example, children who have Down syndrome have an increased risk of AML during the first three years of life. However, the reasons for this increased risk are not well understood.
The rate of AML is highest in children under two years old. The incidence rate increases again in late childhood (during the teenage years) and continues to increase throughout later adulthood.
Children with AML may experience the following symptoms. Sometimes, children 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 child’s doctor.
The early signs and symptoms of AML can look very much like the flu or other common childhood illnesses. Most of the signs and symptoms of AML are the result of poor bone marrow production of normal blood cells and the accumulation of cancerous AML cells. Often one or more of the following symptoms occur:
Doctors use many tests to diagnose leukemia. Some tests may also determine which treatments may be the most effective. Your child’s doctor may consider these factors when choosing a diagnostic test:
Age and medical condition
The type of cancer
Severity of symptoms
Previous test results
When a child shows signs and symptoms of leukemia, the doctor will ask about the child’s medical history and perform a physical examination. In addition to a physical examination, the following tests may be used to diagnose AML:
Blood tests. A blood sample will be taken for testing. Complete blood count (CBC) and cell type (differential count) will be done to count the number of each type of blood cells under the microscope and to determine if they look abnormal.
Bone marrow aspiration and biopsy. A bone marrow aspiration is performed if the blood test shows abnormal blood counts. For this test, after sedation, the child’s skin is numbed with a local anesthetic and a needle is inserted into a bone in the hip until it reaches the spongy part of the bone at the center, the bone marrow. A small amount of bone marrow is removed and examined under a microscope. This is called an aspirate. Your child’s doctor may also use a hollow needle in the same location to withdraw a solid core of bone marrow. This is called a biopsy. This will help tell the doctor if and what type of leukemia is present.
Flow cytometryand immunocytochemistry. Flow cytometry and immunocytochemistry are special laboratory tests that are used to determine the exact subtype of AML (see Subtypes). A flow cytometry involves cells of interest being removed and treated with a fluorescent, dye-equipped antibody that attaches to DNA. The cells are then passed in front of a laser beam, which allows a special computer to measure their DNA level. Higher amounts of DNA than normal may indicate cancer. During an immunocytochemistry test, fluorescent antibodies or immunoperoxidase staining may be used to determine the subtype of AML.
Cytogenetics. Cytogenetics is the analysis of a cell’s chromosomes, including the number, size, shape, and the arrangement of the chromosomes. This examinationmay be used to identify genetic changes present within the leukemia cells. Sometimes, a chromosome (a long strand of genes) breaks off and reattaches to another chromosome; this type of genetic exchange is called a translocation. Other times, part of a chromosome is missing (called a deletion) or sometimes a chromosome is produced more than once (most often called a trisomy). Some leukemias are caused by chromosome translocations, deletions, or trisomies. Knowing if certain translocations are present may help doctors classify the AML subtype and plan the best treatment. Flourescence-in-situ-hybridization (FISH) is a powerful way of detecting chromosome changes in cancer cells and is increasingly used in the diagnosis and subtyping of leukemia. New tests are being developed to study other genetic abnormalities that may be present but cannot be seen in the routine examination of chromosomes. These genetic tests will be done using a sample of the child’s blood or bone marrow.
AML blasts are classified based upon their resemblance to normal, immature bone marrow blast cells and, more recently, upon their cytogenetic origins. In the recent past, AML was divided into eight major subtypes according to a system called the FAB classification scheme (using levels M0 to M7). More recently, a new method of subtyping AML is in use that takes into consideration the cytogenetic causes of AML. This is called the WHO (World Health Organization) classification. These subtypes include:
Acute myeloid leukemia with recurrent genetic abnormalities
Acute myeloid leukemia with t(8;21)(q22;q22), AML1/ETO)
Acute myeloid leukemia with abnormal bone marrow eosinophils and inv(16)(p13q22) or t(16;16)(p13;q22), (CBFß/MYH11)
Acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RARa) and variants
Acute myeloid leukemia with 11q23 (MLL) abnormalities
Acute myeloid leukemia with multilineage dysplasia
Following MDS or MDS/MPD
Without antecedent MDS or MDS/MPD, but with dysplasia in at least 50% of cells in 2 or more myeloid lineages
Acute myeloid leukemia and myelodysplastic syndromes, therapy related
Alkylating agent/radiation-related type
Topoisomerase II inhibitor-related type (some may be lymphoid)
Others
Acute myeloid leukemia, not otherwise categorized
Classify as:
Acute myeloid leukemia, minimally differentiated (previously called M0)
Acute myeloid leukemia without maturation (previously called M1)
Acute myeloid leukemia with maturation (previously called M2)
Acute myelomonocytic leukemia (previously called M4)
Acute monoblastic/acute monocytic leukemia (previously called M5)
Acute erythroid leukemia (erythroid/myeloid and pure erythroleukemia) (previously called M6)
Acute megakaryoblastic leukemia (previously called M7)
The following terms are used to describe the state of disease in children with AML:
Untreated AML. The child hasn’t received any treatment except to relieve symptoms of the disease. The blood and/or bone marrow contain too many white blood cells, and the child has signs and symptoms of the disease.
Complete Remission AML. The number of cancerous blast cells in the bone marrow is too few to be distinguished from normal blasts under the microscope (fewer than 5% blasts in the bone marrow). The child usually does not have any signs or symptoms of the disease.
Partial Remission AML. The number of cancerous blast cells in the bone marrow is reduced (between 5% and 15% in the bone marrow) but still recognizable under the microscope. The child usually does not have any signs or symptoms of the disease. This applies only during the initial courses of therapy called induction (see below).
Recurrent AML. The disease has recurred (come back) after the child experienced a period of remission (complete absence of symptoms).
Refractory AML. The leukemia did not go into complete remission after treatment.
Most children with AML in the United States participate in clinical trials. Clinical trials are research studies that test new therapies and compare the best treatments available (standard treatments) with newer treatments that may be more effective. Cancer in children is rare, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. Investigating new treatments involves careful monitoring using scientific methods, and all participants are followed closely to track progress. When there is a clear improvement of cure (also called survival) for one treatment over another, then the best proven therapy becomes the new standard treatment.
All children with cancer should be treated at hospitals that can provide the specialized care these children require. Doctors, nurses, and other staff at these centers have extensive experience in treating children with cancer and have access to the latest research. Many times, a team of doctors treats a child with cancer. Children treated for AML need specialized care, so it is important for the treatment team to have experience in treating children with AML.
Pediatric cancer centers often have extra support services for children and their families, such as nutritionists, cancer pharmacists, social workers, and counselors. Special activities for kids with cancer may also be available.
An increasing number of pediatric cancer centers also have services for teenagers and young adults. Sometimes, adult cancer centers also offer clinical trials for teens and young adults with cancer.
Treatments for children with AML
Two types of treatment are commonly used to treat AML in children: chemotherapy and bone marrow transplantation (BMT), also called stem cell transplantation. Sometimes more than one treatment is used.
Chemotherapy
Chemotherapy involves the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. Chemotherapy primarily kills cancer cells because they are the most rapidly dividing cells. Chemotherapy is the primary treatment for AML.
Several treatments have been developed that involve intensive use of several drugs. About 85% of children will have an initial remission, and about 50% will be cured. During treatment, children with AML need to be monitored very carefully and often spend many weeks in the hospital because of very low blood counts and the possibility of developing infections.
Chemotherapy may be given by mouth, injected into a vein, or injected into the cerebrospinal fluid (CSF). The choice of drugs will depend on whether the child has previously been treated for AML before and other factors.
Chemotherapy for AML is usually divided into two phases of treatment: induction and intensification.
Induction chemotherapy uses chemotherapy to kill as many of the cancer cells as possible and to cause the AML to go into remission.
Intensification chemotherapy is another phase to eliminate any remaining cancer cells. Chemotherapy or BMT can be used for intensification therapy.
Because chemotherapy attacks rapidly dividing cells, including those in normal tissues such as the hair, lining of the mouth, intestines, and bone marrow, children receiving chemotherapy may lose their hair, develop mouth sores, or have nausea and vomiting. In addition, chemotherapy may lower the body’s resistance to infection, lead to increased bruising and bleeding, and cause fatigue. These side effects can be controlled during treatment and usually go away after chemotherapy is completed. The severity of the side effects depends on the type and amount of the drug being given and the length of time the child receives the drug. The degree to which children experience side effects may also be affected by other factors, including genetic differences in the way the medications are metabolized and the child’s overall health and well-being. Doctors understand that everyone is unique. Most children are initially treated similarly to other children with the same cancer. However, based upon chemotherapy side effects, doses or schedules may be adjusted. This is a constant balance between the effort to kill all the cancer cells and the need to avoid severe complications. Your doctor will discuss these adjustments with you as they become necessary. Not everyone needs to have their chemotherapy adjusted.
The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.
Bone marrow transplantation/stem cell transplantation
In a bone marrow transplant for AML, a child’s bone marrow and the remaining leukemia cells hiding within it is destroyed with chemotherapy (and sometimes radiation therapy) and replaced by healthy bone marrow. The doctor first gives high doses of chemotherapy (and sometimes radiation therapy) to destroy all of the child’s bone marrow. The doctor then takes healthy marrow or blood stem cells from a donor whose tissue matches the child’s as closely as possible, called an allogenic (ALLO) transplant. The healthy cells are infused into the child’s vein. It finds its way to the bones and replaces the destroyed bone marrow. Bone marrow transplants may also be called stem cell transplants.
The best match for transplantation usually comes from a brother or sister. Occasionally, other relatives can also be matches. Unrelated volunteers can also be matches.
Children with AML have different risks of recurrence (cancer that comes back after treatment) depending upon the subtype of AML. The higher a risk for recurrence, the greater the need to use a BMT. For those children with subtypes of AML that have lower risks of recurrence and therefore higher chances of cure, most can be treated with chemotherapy alone. For children with an average (also called intermediate) risk for recurrence and survival, when a related donor is available, BMT is the preferred choice of treatment after a child experiences a first remission. For those children with the highest risk of recurrence and the poorest chance for survival, either a BMT with a related or unrelated donor is often used in addition to chemotherapy after a child experiences a first remission.
In general, transplantations from unrelated donors are not performed unless the AML has recurred. Clinical trials are studying the use of unrelated donor transplants for patients with AML that has certain high-risk features (for example, a chromosome abnormality called monosomy 7 or a child who doesn’t achieve a complete or partial remission after their first course of induction chemotherapy).
In an autologous (AUTO) BMT, the child’s own bone marrow or blood stem cells are used as the replacement. The tissue is removed and then frozen. The child then receives the high-dose chemotherapy (and sometimes radiation therapy) to kill his or her own bone marrow. The frozen tissue is thawed and infused back into the veins to replace the destroyed marrow. In clinical trials in the United States, autologous BMT has not been proven to be more effective than chemotherapy for AML; therefore, it is not routinely used to treat AML in children.
Not all children with AML need a BMT. Children with Down syndrome and M3 acute promyelocytic leukemia do not need a BMT unless the AML recurs. AML with certain genetic changes (for example, chromosome abnormalities known as inv 16 and t[8;21]) does not need BMT unless the leukemia has recurred. These groups of children have lower risks of recurrence and higher chances of long-term survival with chemotherapy alone.
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 treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. Radiation therapy for AML is generally used only if the cancer has spread to the brain and does not respond to systemic treatment and/or chemotherapy into the spinal fluid. Radiation therapy may also be used to treat chloromas, the solid tumors that AML cells occasionally form. As explained above, radiation therapy may also be used during a bone marrow transplant.
Side effects from radiation therapy include tiredness, mild skin reactions, upset stomach, and loose bowel movements. Radiation therapy can sometimes interfere with the normal growth and development of the child’s brain and body. Therefore, where possible, chemotherapy is first used with the hope to avoid radiation. More information can be found in the After Treatment section.
Recurrent AML
In some children who have received treatment for AML, the disease still comes back after treatment. This is called a recurrence or relapse of AML. Most recurrences occur in the bone marrow, but sometimes may involve the brain or other parts of the body. Treatment usually includes more chemotherapy followed by BMT. Each child’s treatment is planned individually depending on the circumstances. Clinical trials testing new targeted therapies for AML are an option for some children with recurrent AML. In some children, recurrent AML can be cured.
Doctors and scientists are always looking for better ways to treat children with AML. A clinical trial is a way to test a new treatment in order 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 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 children, 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 people 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 child’s health-care team. Before treatment begins, talk with your child’s doctor about possible side effects of the specific treatments your child 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 your doctor about side effects your child experiences 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 Cancer.Net’s 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 Cancer.Net’s 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 child’s doctor.
After treatment for AML ends, talk with your child’s doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your child’s recovery for the coming months and years. All children treated for cancer, including AML, should have life-long, follow-up care.
Based on the type of treatment the child received, the doctor will determine what examinations and tests are needed to check for long-term side effects, such as problems with the heart, lungs, or growth hormones, the development of a learning disability, and the possibility of secondary cancers. While this risk is generally low, your child should be closely monitored for their entire life for these new (secondary) cancers. Your doctor can recommend the necessary screening tests. Follow-up care should also address the child’s quality of life, including any developmental or emotional concerns. Learn more about Late Effects of Childhood Cancer.
The child’s family is encouraged to organize and keep a record of the child’s medical information, so that as the child enters adulthood, he or she has a clear, written history of the diagnosis and details of the treatment given. The doctor’s office can help you compile this, and it should include recommendations from the doctor about the schedule for follow-up care. This information will be valuable to doctors who care for your child during his or her lifetime.
Children who have had cancer can also enhance the quality of their future by following established guidelines for good health into and through adulthood, including not smoking, maintaining a healthy weight, eating a balanced diet, and participating in regular physical activity. Talk with the doctor about developing a plan that is best for your child’s needs.
Research involving more advanced diagnostic procedures and treatment for AML 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.
Genetic testing. Molecular genetic signatures of leukemia cells are being tested to see if they can better define groups of patients who may require more or less intense treatment. Among these, the most promising to help identify who needs more or less chemotherapy and/or BMT, is the Flt3 (pronounced flit 3) mutation identified using molecular genetic testing. It appears that those with a Flt3 mutation called internal tandem duplication (ITD), and specifically, those with a high allelic ratio ITD mutation have a high risk of recurrence. For these children and adults, the use of BMT may be able to improve survival when used after the first complete remission. This mutation and others are being discovered to better understand the causes of leukemia, help in establishing a prognosis for each child, and to help in the development of new agents (drugs) that target these specific mutations to treat cancer.
Better detection. Minimal residual disease (cancer cells not killed by treatment) is being measured by sensitive techniques to detect one leukemic cell in 10,000 normal cells to determine likelihood of recurrence. Adjustment of chemotherapy treatments and/or the use of BMT may in the future be partly based upon these new generations of tests.
New agents. New drugs for the treatment of AML are being studied for children. An example of a new drug that is currently being tested is gemtuzumab ozogamicin (Mylotarg). This drug is an antibody linked to a strong chemotherapy agent that specifically targets AML blasts. It is being tested in combination with chemotherapy for children with newly diagnosed AML. Other new agents that may in the future be used for AML are being tested in clinical trials or are in development in research laboratories around the world. A new class of these agents, often called kinase inhibitors, block the abnormal proteins in cells that are created by the chromosome mutations. By blocking these proteins, it is hoped that the uncontrolled rapid growth of cancer can be halted, and that this can be accomplished without the typical side effects of traditional chemotherapy. Future clinical trials will help determine if this approach is effective.
Regular communication with your child’s doctor is important in making informed decisions about your child’s health care. Consider asking the following questions of your child’s doctor:
What type of leukemia has been diagnosed?
What subtype of leukemia has been diagnosed? What does this mean?
What are the treatment options?
What clinical trials are open to my child?
What treatment do you recommend? Why?
What chemotherapy will my child receive?
Should my child receive a bone marrow transplant?
Will my child receive radiation therapy?
What are the side effects of each treatment, both in the short-term and long-term?
How long will my child stay in the hospital?
What are the chances that the AML will recur?
What support services are available to my child? To my family?
What follow-up tests will be needed, and how often?
Patient Information Resources
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
Candlelighters Childhood Cancer Foundation
3910 Warner St.
Kensington, MD 20895
Toll Free: 800-366-2223
Phone: 301-962-3520 www.candlelighters.org
Children's Hospice International
901 N. Pitt St., Ste. 230
Alexandria, VA 22314
Toll Free: 800-24-CHILD (800-242-4453)
Phone: 703-684-0330 www.chionline.org
The Leukemia and Lymphoma Society
1311 Mamaroneck Ave., Ste. 130
White Plains, NY 10605
Toll Free: 800-955-4572 www.lls.org
Leukemia Research Foundation
3520 Lake Ave., Ste. 202
Wilmette, IL 60091
Phone: 847-424-0600
Toll Free: 888-558-5385 www.leukemia-research.org
Make-A-Wish Foundation
3550 N Central Ave., Ste. 300
Phoenix, AZ 85012
Toll Free: 800-722-9474 www.wish.org
National Childhood Cancer Foundation
440 E Huntington Dr.
P.O. Box 60012
Arcadia, CA 91006-6012
Toll Free: 800-458-NCCF (6223) www.nccf.org
National Children's Cancer Society
1015 Locust, Ste. 600
St. Louis, MO 63101
Toll Free: 800-532-6459
Phone: 314-241-1600 www.nationalchildrenscancersociety.org
National Marrow Donor Program
3001 Broadway St., NE, Ste. 500
Minneapolis, MN 55413
Phone: 800-MARROW2 (800-627-7692)
Pat. Adv.: 888-999-6743 www.marrow.org
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