Leukemia - Acute Myeloid - AML - ChildhoodLast Updated: January 28, 2009 This section has been reviewed and approved by the Cancer.Net Editorial Board, 12/08 Overview
Leukemia is a cancer of the blood. Acute myeloid leukemia (AML) is a type of leukemia and is a cancer of the blood-forming tissue in the bone marrow. AML may also be called acute nonlymphocytic leukemia or acute myelogenous leukemia. Bone marrow is the spongy, red tissue in the inner part of the large 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:
In AML, the bone marrow 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 and uncontrollably, are unable to mature and function like normal blast cells, 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 or tumor, called a chloroma. Both children and adults can have leukemia. This section is about AML that occurs in children, sometimes called pediatric AML. For information on adult AML, please read the Cancer.Net Guide to Leukemia, Acute Myeloid (AML). Statistics In general, leukemia is the most common childhood cancer. AML is the second most common form of leukemia in children, after acute lymphoblastic leukemia (ALL). In 2009, an estimated 885 children ages 0 to 19 in the United States will be diagnosed with AML. Childhood 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 people who survive at least five years after the cancer is detected, excluding those who die from other diseases) for children with AML is more than 50%. 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 intervals, they may not represent advances made in the treatment or diagnosis of this cancer. Source: American Cancer Society Find out more about basic cancer terms used in this section. Medical Illustrations
Risk Factors
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, including AML. Sometimes, AML may be caused by certain genetic or environmental factors. 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. AML occurs most often in children younger than two. The number of people with AML increases again in late childhood (during the teenage years) and continues to increase throughout later adulthood. Symptoms
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 caused by the bone marrow producing fewer normal blood cells and the accumulation of cancerous AML cells. Often one or more of the following symptoms occur:
Diagnosis
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:
When a child has signs and symptoms of leukemia, the doctor will ask about the child’s medical history and perform a physical examination. In addition, the following tests may be used to diagnose AML: Blood tests. Complete blood count (CBC) and cell type (differential count) are blood tests done to count the number of each type of blood cell under a 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 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 the doctor determine if and what type of leukemia is present. Cytochemical and immunohistochemical tests. Cytochemical and immunohistochemical tests are laboratory tests that are used to determine the exact subtype of AML (see Subtypes). In cytochemical tests, a special dye is used that stains the different types of leukemia cells differently based on the chemical contents of the cells. Immunohistochemical tests for AML are used to identify markers on the surface of the leukemia cells. The different subtypes of leukemia have different and unique combinations of cell surface markers. Cytogenetics/genetic testing. Cytogenetics is the analysis of a cell’s chromosomes, including the number, size, shape, and the arrangement of the chromosomes. This examination may be used to identify genetic changes in the leukemia cells. Sometimes, a chromosome (a long strand of genes) breaks off and reattaches to another chromosome (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 subtypes of leukemia 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. Molecular genetic signatures of leukemia cells can also be used to help identify if a person needs more or less chemotherapy and/or stem cell transplantation. People with the Flt3 (pronounced flit 3) genetic mutation, called internal tandem duplication (ITD), and specifically, those with a high allelic ratio ITD mutation have a high risk that the cancer will come back after treatment. For these children and adults, the use of stem cell transplantation may improve survival when used after the first complete remission (see Treatment). New tests are being developed to study other genetic changes 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. To learn more about what to expect during common diagnostic tests, read Cancer.Net: Tests and Procedures. To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Newly Diagnosed. Subtypes
AML blasts are classified based on how much they look like normal, immature bone marrow blast cells and, more recently, on cytogenetics. 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 used that takes into consideration the cytogenetic causes of AML. This is called the WHO (World Health Organization) classification. These subtypes include:
Treatment
The following terms are used to describe the state of disease for children with AML: Untreated AML. The child has not 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 course of therapy called induction (see below). Recurrent AML. The disease has 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. Treatments for children with AML Two types of treatment are commonly used to treat AML in children: chemotherapy and stem cell transplantation/bone marrow transplantation; both are described below in detail. Radiation therapy is occasionally used in specific situations. Sometimes, more than one treatment is used. Clinical Trials are the standard of care for the treatment of children with cancer. In fact, more than 60% of children with cancer are treated as part of a clinical trial. Clinical trials are research studies that compare standard treatments (the best treatments available) 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. To take advantage of these newer treatments, all children with cancer should be treated at a specialized cancer center. Doctors 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. Pediatric cancer centers often have extra support services for children and their families, such as nutritionists, 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. Chemotherapy Chemotherapy is 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 most common treatment for AML. Several treatment plans have been developed that involve intensive use of several drugs. Following these plans, 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 depends on whether the child has previously been treated for AML 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 cause the AML to go into remission. Intensification chemotherapy is used to kill any cancer cells remaining after induction chemotherapy. Stem cell transplantation also can be used for intensification therapy. The side effects of chemotherapy depend on the individual and the dose used, but can include fatigue, low blood counts, risk of infection, hair loss, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished. The severity of side effects may also be affected by other factors, including genetic differences in the way the drugs are processed by the body 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 on the side effects, doses or schedules may be changed. 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 changes with you as they become necessary. Not everyone needs to have their chemotherapy changed. 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 your child, their purpose, and their potential side effects or interactions with other medications. Learn more about your child’s prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases. Stem cell transplantation/bone marrow transplantation Children with AML have different risks of recurrence depending on the subtype. The higher a risk for recurrence, the greater the consideration to use a stem cell transplantation. Not all children with AML need stem cell transplantation. For instance, children with Down syndrome and M3 acute promyelocytic leukemia do not need stem cell transplantation unless the AML recurs. AML with certain genetic changes (for example, chromosome abnormalities known as inv 16 and t[8;21]) is not treated with stem cell transplantation unless the leukemia has recurred. For children with subtypes of AML that have lower risks of recurrence and therefore higher chances of cure, most can be treated with chemotherapy alone. 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 the cells that normally become bone marrow. They are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant as stem cells from either the blood or the bone marrow may be used. There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO transplantation is the type used mainly for AML. AUTO stem cell transplantation is not a standard treatment for AML in the United States except for patients with recurrent M3 acute promyelocytic leukemia. 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, a donation of stem cells derived from umbilical cord blood is sometimes considered if family donors are not available. For children with an average (also called intermediate) risk for recurrence and survival, when a related donor is available, stem cell transplantation is the preferred choice of treatment after a child has a first remission. For children with the highest risk of recurrence and the poorest chance for survival, stem cell transplantation with either a related or unrelated donor is often used in addition to chemotherapy after the child has 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 have a complete or partial remission after their first course of induction chemotherapy). 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. Learn more by reading the Cancer.Net Feature series Understanding Bone Marrow and Stem Cell Transplantation. 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 chemotherapy and/or chemotherapy given into the spinal fluid. Radiation therapy may also be used to treat a chloroma. As explained above, radiation therapy may also be used during a stem cell/bone marrow transplant. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Radiation therapy can sometimes interfere with the normal growth and development of the child’s brain and body. Therefore, when possible, chemotherapy is used first to avoid radiation therapy. More information can be found in the After Treatment section. Recurrent AML For some children who received treatment for AML, the disease comes back after treatment. Most recurrences occur in the bone marrow, but sometimes it may come back in the brain or other parts of the body. Treatment usually includes chemotherapy followed by stem cell transplantation. 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. For some children, recurrent AML can be cured. To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment. Clinical Trials Resources
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 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. Side Effects
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 child’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
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 secondary cancers. Your child’s 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 Childhood Cancer Survivorship. 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. To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: After Treatment. Current Research
Research for AML is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Always discuss all diagnostic and treatment options with your child’s 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. These discoveries help doctors better understand the causes of leukemia, help establish a prognosis for each child, and help in the development of new drugs that target these specific genetic mutations. Better detection. Minimal residual disease (cancer cells not killed by treatment) is being measured using sensitive techniques to detect one leukemic cell in 10,000 normal cells to determine the likelihood of recurrence. In the future, changes made to chemotherapy treatments and/or the use of stem cell transplantation may be partly based on these new types of tests. New drugs and combinations of drugs. New types of drugs, called targeted therapy, target faulty genes or proteins that contribute to cancer growth and development. Gemtuzumab (Mylotarg) is an antibody that specifically targets AML blasts. It is being tested in combination with chemotherapy for children with newly diagnosed AML. Other new drugs that may be used for AML are being tested in clinical trials or are in development in research laboratories around the world. Questions to Ask the Doctor
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:
Patient Information Resources
The Leukemia and Lymphoma Society Leukemia Research Foundation Stem cell transplantation/bone marrow transplantation resources American Society for Blood and Marrow Transplantation Blood and Marrow Transplant Information Network National Bone Marrow Transplant Link National Marrow Donor Program General childhood cancer resources Candlelighters Childhood Cancer Foundation Children's Hospice International Make-A-Wish Foundation CureSearch National Children's Cancer Society Outlook: Life Beyond Childhood Cancer The Children's Cause for Cancer Advocacy The Starlight Children's Foundation View all of Cancer.Net's Patient Information Resources. |
