Leukemia, acute myeloid, childhood: Treatment - Patient Information [NCI PDQ]

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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®)

General Information About Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Leukemia and other diseases of the blood and bone marrow may affect red blood cells, white blood cells, and platelets.

Normally, the bone marrow makes stem cells (immature cells) that develop into mature blood cells. There are three types of mature blood cells:

• Red blood cells that carry oxygen and other materials to all tissues of the body.
• White blood cells that fight infection and disease.
• Platelets that help prevent bleeding by causing blood clots to form.

Childhood acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes a large number of abnormal blood cells.

Cancers that are "acute" usually get worse quickly if they are not treated. Cancers that are "chronic" usually get worse slowly. Acute myeloid leukemia (AML) is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, or acute nonlymphocytic leukemia.

In AML, the stem cells usually develop into a type of white blood cell called myeloblasts (or myeloid blasts). The myeloblasts, or leukemia cells, in AML are abnormal and do not mature into healthy white blood cells. These blood cells are unable to do their usual work and can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or easy bleeding may occur. The leukemia cells can spread outside the blood to other parts of the body, including the central nervous system (brain and spinal cord), skin, and gums. Sometimes leukemia cells form a solid tumor called a granulocytic sarcoma or chloroma.

There are subtypes of AML based on the type of blood cell that is affected. The treatment of AML is different when it is a subtype called acute promyelocytic leukemia (APL) or when the child has Down syndrome.

Other myeloid diseases can affect the blood and bone marrow.

Chronic myelogenous leukemia

In chronic myelogenous leukemia (CML), too many bone marrow stem cells develop into a type of white blood cell called granulocytes. Some of these bone marrow stem cells never become mature white blood cells. These are called blasts. Over time, the granulocytes and blasts crowd out the red blood cells and platelets in the bone marrow. CML is rare in children.

Juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a rare childhood cancer that occurs more often in children younger than 2 years. In JMML, too many bone marrow stem cells develop into 2 types of white blood cells called myelocytes and monocytes. Some of these bone marrow stem cells never become mature white blood cells. These immature cells, called blasts, are unable to do their usual work. Over time, the myelocytes, monocytes, and blasts crowd out the red blood cells and platelets in the bone marrow. When this happens, infection, anemia, or easy bleeding may occur.

Transient myeloproliferative disorder

Transient myeloproliferative disorder (TMD) is a disorder of the bone marrow that can develop in newborns who have Down syndrome. This disorder usually goes away on its own within the first 3 weeks of life. Infants who have Down syndrome and TMD have an increased chance of developing AML before the age of 3 years.

Myelodysplastic syndromes

In myelodysplastic syndromes, the bone marrow makes too few red blood cells, white blood cells, and platelets. These blood cells may not mature and enter the blood. The treatment for myelodysplastic syndromes depends on how much lower than normal the number of red blood cells, white blood cells, or platelets is. Myelodysplastic syndromes may progress to AML.

This summary is about childhood AML, childhood CML, JMML, TMD, and myelodysplastic syndromes. See the following PDQ summaries for more information about other types of leukemia and diseases of the blood and bone marrow:

• Adult Acute Myeloid Leukemia Treatment
• Chronic Myelogenous Leukemia Treatment
• Adult Acute Lymphoblastic Leukemia Treatment
• Childhood Acute Lymphoblastic Leukemia Treatment
• Chronic Lymphocytic Leukemia Treatment
• Hairy Cell Leukemia Treatment
• Myelodysplastic Syndromes Treatment
• Myelodysplastic and Myeloproliferative Diseases Treatment

The risk factors for developing childhood AML, childhood CML, JMML, TMD, and myelodysplastic syndrome are similar.

Anything that increases your risk of getting a disease is called a risk factor. Possible risk factors for childhood AML, childhood CML, JMML, TMD, and myelodysplastic syndrome include the following:

• Having a brother or sister, especially a twin, with leukemia.
• Being Hispanic.
• Being exposed to cigarette smoke or alcohol before birth.
• Having a history of myelodysplastic syndrome (also called preleukemia) or aplastic anemia.
• Past treatment with chemotherapy or radiation therapy.
• Being exposed to ionizing radiation or chemicals such as benzene.
• Having certain genetic disorders, such as Down syndrome, Fanconi anemia, neurofibromatosis type 1, or Noonan syndrome.

Possible signs of childhood AML, childhood CML, JMML, or myelodysplastic syndromes include fever, feeling tired, and easy bleeding or bruising.

These and other symptoms may be caused by childhood AML, childhood CML, JMML, or myelodysplastic syndromes. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

• Fever with or without an infection.
• Night sweats.
• Shortness of breath.
• Weakness or feeling tired.
• Easy bruising or bleeding.
• Petechiae (flat, pinpoint spots under the skin caused by bleeding).
• Pain in the bones or joints.
• Pain or feeling of fullness below the ribs.
• Painless lumps in the neck, underarm, stomach, groin, or other parts of the body. When seen in childhood AML, these lumps, called leukemia cutis, may be blue or purple.
• Painless lumps that are sometimes around the eyes. These lumps, called chloromas, are sometimes seen in childhood AML and may be blue-green.
• An eczema-like skin rash.

The symptoms of TMD may include the following:

• Swelling all over the body.
• Shortness of breath.
• Trouble breathing.
• Weakness or feeling tired.
• Pain below the ribs.

Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood AML, childhood CML, JMML, TMD, and myelodysplastic syndromes.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the sample made up of red blood cells.
  
  
  Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• Peripheral blood smear: A procedure in which a sample of blood is checked for blast cells, number and kinds of white blood cells, number of platelets, and changes in the shape of the blood cells.
• Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. Biopsies that may be done for childhood AML include the following:
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a needle into the hipbone or breastbone.
  • Tumor biopsy: A biopsy of a chloroma may be done.
  • Lymph node biopsy: The removal of all or part of a lymph node.
• Cytogenetic analysis: A test in which cells in a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes.
• Immunophenotyping: A process used to identify cells, based on the types of antigens or markers on the surface of the cell, that may include special staining of the blood and bone marrow cells. This process is used to diagnose the subtype of AML by comparing the cancer cells to normal cells of the immune system.
• Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options for childhood AML depend on the following:

• Number of white blood cells in the blood at diagnosis.
• Whether the AML was caused by previous anticancer treatment.
• The subtype of AML.
• Whether there are certain chromosomal changes in the leukemia cells.
• Whether the child has Down syndrome. Most children with AML and Down syndrome can be cured of their leukemia.
• How well the leukemia responds to initial treatment.
• Whether the AML is newly diagnosed or has recurred (come back) after being treated.
• The length of time since treatment ended, for AML that has recurred.

The prognosis and treatment options for childhood CML depend on how long it has been since the patient was diagnosed and how many blast cells are in the blood.

The prognosis (chance of recovery) and treatment options for JMML depend on the following:

• The age of the child at diagnosis.
• How many red blood cells, white blood cells, or platelets are in the blood.
• Whether the JMML is untreated or has recurred after treatment.

The prognosis (chance of recovery) and treatment options for myelodysplastic syndromes depend on the following:

• Whether the myelodysplastic syndrome was caused by previous cancer treatment.
• How low the numbers of red blood cells, white blood cells, or platelets are.
• Whether the myelodysplastic syndrome is untreated or has recurred after treatment.

Stages of Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Once childhood acute myeloid leukemia (AML) has been diagnosed, tests are done to find out if the cancer has spread to other parts of the body.

The extent or spread of cancer is usually described as stages. In childhood acute myeloid leukemia (AML), the subtype of AML and whether the leukemia has spread outside the blood and bone marrow are used, instead of the stage, to plan treatment. The following tests and procedures may be used to determine if the leukemia has spread:

• Lumbar puncture: A procedure used to collect cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
• Biopsy of the testicles, ovaries, or skin: The removal of cells or tissues from the testicles, ovaries, or skin so they can be viewed under a microscope to check for signs of cancer. This is done only if something unusual about the testicles, ovaries, or skin is found during the physical exam.

There is no standard staging system for childhood AML, childhood chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), transient myeloproliferative disorder (TMD), or myelodysplastic syndromes (MDS).

Childhood AML is described as newly diagnosed, in remission, or recurrent.

NEWLY DIAGNOSED CHILDHOOD AML

Newly diagnosed childhood AML has not been treated except to relieve symptoms such as fever, bleeding, or pain, and one of the following is true:

• More than 20% of the cells in the bone marrow are blasts (leukemia cells).

  or

• Less than 20% of the cells in the bone marrow are blasts and there is a specific change in the chromosome.

CHILDHOOD AML IN REMISSION

In childhood AML in remission, the disease has been treated and the following are true:

• The complete blood count is almost normal.
• Less than 5% of the cells in the bone marrow are blasts (leukemia cells).
• There are no signs or symptoms of leukemia in the brain, spinal cord, or other parts of the body.

Recurrent Childhood Acute Myeloid Leukemia

Recurrent childhood acute myeloid leukemia (AML) has recurred (come back) after it has been treated. The cancer may come back in the blood and bone marrow or in other parts of the body.

Treatment Option Overview

There are different types of treatment for children with acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), transient myeloproliferative disorder (TMD), or myelodysplastic syndromes.

Different types of treatment are available for children with AML, CML, JMML, TMD, or myelodysplastic syndromes. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

Children with AML, CML, JMML, TMD, or myelodysplastic syndromes should have their treatment planned by a team of doctors with expertise in treating childhood leukemia and other diseases of the blood.

Your child's treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist may refer you to other pediatric doctors who have experience and expertise in treating children with leukemia and who specialize in certain areas of medicine. These may include the following specialists:

• Hematologist.
• Medical oncologist.
• Pediatric surgeon.
• Radiation oncologist.
• Neurologist.
• Neuropathologist.
• Neuroradiologist.
• Pediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.

Regular follow-up exams are very important. Some cancer treatments cause side effects that continue or appear years after cancer treatment has ended. These are called late effects. Late effects of cancer treatment may include the following:

• Physical problems.
• Changes in mood, feelings, thinking, learning, or memory.
• Having a new type of cancer.

Some late effects may be treated or controlled. It is important that parents of children who are treated for AML or other blood diseases talk with their doctors about the possible late effects caused by some treatments. See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.

The treatment of childhood AML usually has two phases.

The treatment of childhood AML is done in phases:

• Induction therapy: This is the first phase of treatment. Its purpose is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission.
• Consolidation/intensification therapy: This is the second phase of treatment. It begins once the leukemia is in remission. The purpose of postremission therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse.

Treatment called central nervous system (CNS) sanctuary therapy may be given during the induction phase of therapy. Because chemotherapy that is given by mouth or injected into a vein may not reach leukemia cells in the CNS (brain and spinal cord), the cells are able to find "sanctuary" (hide) in the CNS. Intrathecal chemotherapy and radiation therapy are able to reach and kill leukemia cells in the CNS and prevent the cancer from recurring (coming back). CNS sanctuary therapy is also called CNS prophylaxis.

Six types of standard treatment are used for childhood AML, childhood CML, JMML, TMD, or myelodysplastic syndromes.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug.

The way the chemotherapy is given depends on the type of cancer being treated.

In AML, the leukemia cells may spread to the brain and/or spinal cord. Chemotherapy given by mouth or vein to treat AML cannot cross the blood-brain barrier and enter the fluid that surrounds the brain and spinal cord. Instead, intrathecal chemotherapy is injected into the fluid-filled space to kill leukemia cells that may have spread there.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. External radiation therapy may be used to treat childhood AML that has spread, or may spread, to the brain and spinal cord. When used this way, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.

Stem cell transplantation

Stem cell transplant is a way of giving chemotherapy and replacing blood-forming cells that are abnormal or destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

Other drug therapy

Arsenic trioxide and all-trans retinoic acid (ATRA) are anticancer drugs that kill leukemia cells, stop the leukemia cells from dividing, or help the leukemia cells mature into white blood cells. These drugs are used in the treatment of a subtype of AML called acute promyelocytic leukemia (APL).

Imatinib (Gleevec) is a type of anticancer drug called a tyrosine kinase inhibitor. It blocks the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells (granulocytes or blasts) than the body needs.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change. It is sometimes used to treat myelodysplastic syndromes or TMD.

Supportive care

Supportive care is given to lessen the problems caused by the disease or its treatment. Supportive care may include the following:

• Transfusion therapy: A way of giving red blood cells, white blood cells, or platelets to replace blood cells destroyed by disease or cancer treatment. The blood may be donated from another person or it may have been taken from the person earlier and stored until needed.
• Drug therapy, such as antibiotics.
• Leukapheresis: A procedure in which a special machine is used to remove white blood cells from the blood. Blood is taken from the patient and put through a blood cell separator where the white blood cells are removed. The rest of the blood is then returned to the patient's bloodstream.

New types of treatment are being tested in clinical trials. These include the following:

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Monoclonal antibody therapy is a certain type of biologic therapy. Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Treatment Options for Childhood Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Juvenile Myelomonocytic Leukemia

Newly Diagnosed Childhood Acute Myeloid Leukemia

Treatment of newly diagnosed childhood acute myeloid leukemia (AML) is combination chemotherapy. CNS sanctuary therapy is intrathecal chemotherapy with or without radiation therapy to the brain.

Treatment of newly diagnosed childhood acute leukemia with a granulocytic sarcoma (chloroma) may include chemotherapy with or without radiation therapy.

Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated childhood acute myeloid leukemia and other myeloid malignancies.

Childhood Acute Myeloid Leukemia in Remission

Treatment of childhood acute myeloid leukemia (AML) during the remission phase (consolidation/intensification therapy) depends on the subtype of AML and may include the following:

• Combination chemotherapy.
• Stem cell transplant.
• A clinical trial of chemotherapy with or without a monoclonal antibody.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood acute myeloid leukemia in remission.

Recurrent Childhood Acute Myeloid Leukemia

Treatment of recurrent childhood acute myeloid leukemia (AML) may include the following:

• Combination chemotherapy
• Combination chemotherapy and stem cell transplant.
• A clinical trial of a new anticancer drug.
• A clinical trial of a new monoclonal antibody.
• A clinical trial of stem cell transplant using different sources of stem cells.

Treatment of recurrent acute promyelocytic leukemia may include all-trans retinoic acid (ATRA) or arsenic trioxide therapy

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood acute myeloid leukemia.

Acute Promyelocytic Leukemia

Treatment of acute promyelocytic leukemia may include the following:

• All-trans retinoic acid (ATRA) plus chemotherapy.
• Arsenic trioxide therapy.
• Combination chemotherapy.
• A clinical trial of chemotherapy and ATRA with or without arsenic trioxide.
• A clinical trial of a monoclonal antibody with ATRA.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood acute promyelocytic leukemia (M3).

Children with Down Syndrome and AML

Treatment of AML in children who have Down syndrome may include the following:

• Combination chemotherapy.
• A clinical trial of lower-dose chemotherapy.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Childhood Chronic Myelogenous Leukemia

Treatment for childhood chronic myelogenous leukemia may include the following:

• Stem cell transplant.
• Drug therapy with Gleevec.
• A clinical trial of Gleevec therapy with interferon or chemotherapy.
• A clinical trial of stem cell transplant using lower doses of chemotherapy.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood chronic myelogenous leukemia.

Juvenile Myelomonocytic Leukemia

Treatment of juvenile myelomonocytic leukemia may include the following:

• Stem cell transplant.
• A clinical trial of new combinations of chemotherapy and stem cell transplant.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with juvenile myelomonocytic leukemia.

Transient Myeloproliferative Disorder

Transient myeloproliferative disorder (TMD) usually goes away on its own. For TMD that does not go away on its own, treatment may include the following:

• Transfusion therapy.
• Leukapheresis.
• Chemotherapy.

Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with acute myeloid leukemia/transient myeloproliferative disorder.

Myelodysplastic Syndromes

Treatment of myelodysplastic syndromes may include the following:

• Stem cell transplant.
• Combination chemotherapy.
• A clinical trial of a new anticancer drug.

Supportive care treatments are used to manage problems caused by the disease, such as infection, bleeding, and anemia.

If the myelodysplastic syndrome progresses to acute myeloid leukemia (AML), treatment will be the same as treatment for the newly diagnosed patient with AML.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood myelodysplastic syndromes.

Changes to This Summary (09/28/2007)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made and images were added to this summary.

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Date Last Modified: 2007-09-28

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