Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version - National Cancer Institute

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

General Information About Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

KEY POINTS

Childhood acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes a large number of abnormal blood cells.
Leukemia and other diseases of the blood and bone marrow may affect red blood cells, white blood cells, and platelets.
Other myeloid diseases can affect the blood and bone marrow.
- Transient abnormal myelopoiesis (TAM)
- Acute promyelocytic leukemia (APL)
- Juvenile myelomonocytic leukemia (JMML)
- Chronic myelogenous leukemia (CML)
- Myelodysplastic syndromes (MDS)
AML or MDS may occur after treatment with certain chemotherapy drugs and/or radiation therapy.
The risk factors for childhood AML, APL, JMML, CML, and MDS are similar.
Signs and symptoms of childhood AML, APL, JMML, CML, or MDS include fever, feeling tired, and easy bleeding or bruising.
Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood AML, TAM, APL, JMML, CML, and MDS.
Certain factors affect prognosis (chance of recovery) and treatment options.

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

Childhood acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia. Cancers that are acute usually get worse quickly if they are not treated. Cancers that are chronic usually get worse slowly.

Anatomy of the bone; drawing shows spongy bone, red marrow, and yellow marrow. A cross section of the bone shows compact bone and blood vessels in the bone marrow. Also shown are red blood cells, white blood cells, platelets, and a blood stem cell. — Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone makes up the outer layer of the bone. Spongy bone is found mostly at the ends of bones and contains red marrow. Bone marrow is found in the center of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow marrow is made mostly of fat.

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 blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoidstem cell. A lymphoid stem cell becomes a white blood cell.

A myeloid stem cell becomes one of three types of mature blood cells:

Red blood cells that carry oxygen and other substances to all tissues of the body.
White blood cells that fight infection and disease.
Platelets that form blood clots to stop bleeding.

Blood cell development; drawing shows the steps a blood stem cell goes through to become a red blood cell, platelet, or white blood cell. A myeloid stem cell becomes a red blood cell, a platelet, or a myeloblast, which then becomes a granulocyte (the types of granulocytes are eosinophils, basophils, and neutrophils). A lymphoid stem cell becomes a lymphoblast and then becomes a B-lymphocyte, T-lymphocyte, or natural killer cell. — Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

In AML, the myeloid stem cells usually become a type of immature white blood cell called myeloblasts (or myeloid blasts). The myeloblasts, or leukemia cells, in AML are abnormaland do not become healthy white blood cells. The leukemia cells 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.

Other myeloid diseases can affect the blood and bone marrow.

Transient abnormal myelopoiesis (TAM)

TAM is a disorder of the bone marrow that can develop in newborns who have Down syndrome. It usually goes away on its own within the first 3 months of life. Infants who have TAM have an increased chance of developing AML before the age of 3 years. TAM is also called transient myeloproliferative disorder or transient leukemia.

Acute promyelocytic leukemia (APL)

APL is a subtype of AML. In APL, some genes on chromosome 15 switch places with some genes on chromosome 17 and an abnormal gene called PML-RARA is made. The PML-RARAgene sends a message that stops promyelocytes (a type of white blood cell) from maturing. The promyelocytes (leukemia cells) can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. Problems with severe bleeding and blood clots may also occur. This is a serious health problem that needs treatment as soon as possible.

Juvenile myelomonocytic leukemia (JMML)

JMML is a rare childhood cancer that is most common in children around the age of 2 years and is more common in boys. In JMML, too many myeloid blood stem cells become myelocytes and monocytes (two types of white blood cells). Some of these myeloid blood 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.

Chronic myelogenous leukemia (CML)

CML often begins in an early myeloid blood cell when a certain gene change occurs. A section of genes, that includes the ABL gene, on chromosome 9 changes place with a section of genes on chromosome 22, which has the BCR gene. This makes a very short chromosome 22 (called the Philadelphia chromosome) and a very long chromosome 9. An abnormal BCR-ABL gene is formed on chromosome 22. The BCR-ABL gene tells the blood cells to make too much of a protein called tyrosine kinase. Tyrosine kinase causes too many white blood cells (leukemia cells) to be made in the bone marrow. The leukemia cells 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. CML is rare in children.

Philadelphia chromosome; three-panel drawing shows a piece of chromosome 9 and a piece of chromosome 22 breaking off and trading places, creating a changed chromosome 22 called the Philadelphia chromosome. In the left panel, the drawing shows a normal chromosome 9 with the ABL gene and a normal chromosome 22 with the BCR gene. In the center panel, the drawing shows chromosome 9 breaking apart in the ABL gene and chromosome 22 breaking apart below the BCR gene. In the right panel, the drawing shows chromosome 9 with the piece from chromosome 22 attached and chromosome 22 with the piece from chromosome 9 containing part of the ABL gene attached. The changed chromosome 22 with the BCR-ABL gene is called the Philadelphia chromosome. — Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The BCR-ABL gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.

Myelodysplastic syndromes (MDS)

MDS occur less often in children than in adults. In MDS, 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 type of MDS depends on the type of blood cell that is affected.

The treatment for MDS depends on how low the numbers of red blood cells, white blood cells, or platelets are. Over time, MDS may become AML.

This summary is about childhood AML, TAM, childhood APL, JMML, childhood CML, and childhood MDS. See the Childhood Acute Lymphoblastic Leukemia Treatment summary for information about the treatment of childhood acute lymphoblastic leukemia.

AML or MDS may occur after treatment with certain chemotherapy drugs and/or radiation therapy.

Cancer treatment with certain chemotherapy drugs and/or radiation therapy may cause therapy-related AML (t-AML) or therapy -related MDS (t-MDS). The risk of these therapy-related myeloid diseases depends on the total dose of the chemotherapy drugs used and the radiation dose and treatment field. Some patients also have an inherited risk for t-AML and t-MDS. These therapy-related diseases usually occur within 7 years after treatment, but are rare in children.

The risk factors for childhood AML, APL, JMML, CML, and MDS are similar.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your child’s doctor if you think your child may be at risk. These and other factors may increase the risk of childhood AML, APL, JMML, CML, and MDS:

Having a brother or sister, especially a twin, with leukemia.
Being Hispanic.
Being exposed to cigarette smoke or alcohol before birth.
Having a personal history of aplastic anemia.
Having a personal or family history of MDS.
Having a family history of AML.
Past treatment with chemotherapy or radiation therapy.
Being exposed to ionizing radiation or chemicals such as benzene.
Having certain syndromes or inherited disorders, such as:
- Down syndrome.
- Aplastic anemia.
- Fanconi anemia.
- Neurofibromatosis type 1.
- Noonan syndrome.
- Shwachman-Diamond syndrome.
- Li-Fraumeni syndrome.

Signs and symptoms of childhood AML, APL, JMML, CML, or MDS include fever, feeling tired, and easy bleeding or bruising.

These and other signs and symptoms may be caused by childhood AML, APL, JMML, CML, or MDS or by other conditions. Check with a doctor if your child has any of the following:

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. 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 signs and symptoms of TAM may include the following:

Swelling all over the body.
Shortness of breath.
Trouble breathing.
Weakness or feeling tired.
Bleeding a lot, even from a small cut.
Petechiae (flat, pinpoint spots under the skin caused by bleeding).
Pain below the ribs.
Skin rash.
Jaundice (yellowing of the skin and whites of the eyes).
Headache, trouble seeing, and confusion.

Sometimes TAM does not cause any symptoms at all and is diagnosed after a routine blood test.

Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood AML, TAM, APL, JMML, CML, and MDS.

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) with differential: A procedure in which a sample of blood is drawn and checked for the following:
- The number of red blood cells and platelets.
- The number and type of white blood cells.
- The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
- The portion of the blood sample made up of red blood cells.
ENLARGE
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.
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.
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 include the following:
- Bone marrow aspiration and biopsy : The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone.
  ENLARGE
  Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the child’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
- Tumor biopsy: A biopsy of a chloroma may be done.
- Lymph node biopsy: The removal of all or part of a lymph node.
Immunophenotyping : A process used to identify cells, based on the types of antigensor 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.
Cytogenetic analysis : A laboratory 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. Changes in the chromosomes include when part of one chromosome is switched with part of another chromosome, part of one chromosome is missing or repeated, or part of one chromosome is turned upside down.
The following test is a type of cytogenetic analysis:
- FISH (fluorescence in situ hybridization): A laboratory technique used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light.
Molecular testing : A laboratory test to check for certain genes, proteins, or other molecules in a sample of blood or bone marrow. Molecular tests also check for certain changes in a gene or chromosome that may cause or affect the chance of developing AML. A molecular test may be used to help plan treatment, find out how well treatment is working, or make a prognosis.
Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that leukemia cells have spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.
ENLARGE
Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.

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:

The age of the child when the cancer is diagnosed.
The race or ethnic group of the child.
Whether the child is greatly overweight.
Number of white blood cells in the blood at diagnosis.
Whether the AML occurred after previous cancer treatment.
The subtype of AML.
Whether there are certain chromosome or gene changes in the leukemia cells.
Whether the child has Down syndrome. Most children with AML and Down syndrome can be cured of their leukemia.
Whether the leukemia is in the central nervous system (brain and spinal cord).
How quickly the leukemia responds to treatment.
Whether the AML is newly diagnosed (untreated) or has recurred after treatment.
The length of time since treatment ended, for AML that has recurred.

The prognosis for childhood APL depends on the following:

Number of white blood cells in the blood at diagnosis.
Whether there are certain chromosome or gene changes in the leukemia cells.
Whether the APL is newly diagnosed (untreated) or has recurred after treatment.

The prognosis and treatment options for JMML depend on the following:

The age of the child when the cancer is diagnosed.
The type of gene affected and the number of genes that have changes.
How many monocytes (a type of white blood cell) are in the blood.
How much hemoglobin is in the blood.
Whether the JMML is newly diagnosed (untreated) or has recurred after treatment.

The prognosis and treatment options for childhood CML depend on the following:

How long it has been since the patient was diagnosed.
How many blast cells are in the blood.
Whether and how fully the blast cells disappear from the blood and bone marrow after therapy has started.
Whether the CML is newly diagnosed (untreated) or has recurred after treatment.

The prognosis and treatment options for MDS depend on the following: