Childhood Acute Myeloid Leukaemia and Other Myeloid Malignancies

• Childhood acute myeloid leukaemia (AML) is a type of cancer in which the bone marrow makes a large number of abnormal blood cells.
• There are different subtypes of childhood AML.
• Myelodysplastic syndromes are caused by changes in the blood-forming cells of the bone marrow. They are not a type of leukaemia.
• Juvenile myelomonocytic leukaemia (JMML) is a type of cancer in which the bone marrow makes too many white blood cells.
• Exposure to radiation and a history of myelodysplastic syndrome or aplastic anemia may affect the risk of developing childhood AML.
• Possible signs of childhood AML, myelodysplastic syndromes, or JMML 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, myelodysplastic syndromes, or JMML.
• Certain factors affect prognosis (chance of recovery) and treatment options.

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

Childhood acute myeloid leukaemia (AML) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. AML is also called acute myelogenous leukaemia, acute myeloblastic leukaemia, acute granulocytic leukaemia, or acute nonlymphocytic leukaemia.

Other diseases that affect the blood and bone marrow are myelodysplastic syndromes and juvenile myelomonocytic leukaemia (JMML).

Normally, the bone marrow produces 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.

In AML, the stem cells usually develop into a type of white blood cell called myeloblasts (or myeloid blasts). The myeloblasts, or leukaemia cells, in AML are abnormal and do not mature into healthy white blood cells. Leukaemia 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 leukaemia cells can spread outside the blood to other parts of the body, including the central nervous system (brain and spinal cord), skin, and gums.

This summary is about childhood AML, myelodysplastic syndromes, and JMML. Refer to the following summaries for more information about other types of leukaemia and diseases of the blood and bone marrow:

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

There are different subtypes of childhood AML.

The subtypes of AML are based on the type of blood cell that is affected, how mature (developed) the cancer cells are at the time of diagnosis, and how different they are from normal cells. The treatment for most subtypes of AML is similar. One subtype of AML, acute promyelocytic leukaemia (APL), is treated differently from other types of AML.

Myelodysplastic syndromes are caused by changes in the blood-forming cells of the bone marrow. They are not a type of leukaemia.

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.

Juvenile myelomonocytic leukaemia (JMML) is a type of cancer in which the bone marrow makes too many white blood cells.

Juvenile myelomonocytic leukaemia (JMML) is a rare childhood cancer that occurs more often in children younger than 2 years. In JMML, the bone marrow makes too many white blood cells. The white 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.

Exposure to radiation and a history of myelodysplastic syndrome or aplastic anemia may affect the risk of developing childhood AML.

Possible risk factors for AML include the following:

• Having a brother or sister, especially a twin, with leukaemia.
• Being Hispanic.
• Being exposed to cigarette smoke or alcohol before birth.
• Having a history of myelodysplastic syndrome (also called preleukaemia) 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.

Possible risk factors for myelodysplastic syndromes include the following:

• 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 or Fanconi's anemia.

One possible risk factor for JMML is having certain genetic disorders such as neurofibromatosis type 1 or Noonan's syndrome.

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

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

• Fever with or without an infection.
• 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 leukaemia 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.

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

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:
o The number of red blood cells, white blood cells, and platelets.
o The amount of haemoglobin (the protein that carries oxygen) in the red blood cells.
o The portion of the sample made up of red blood cells.

• 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 produces it.
• 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 to check for signs of cancer. Biopsies that may be done for childhood AML include the following:
o Bone marrow aspiration and biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views both the bone marrow biopsy and the bone marrow aspiration samples under a microscope to look for abnormal cells.
o Tumour biopsy: A biopsy of a chloroma may be done.
o Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells.

• Cytogenetic analysis: A test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if there are changes in the structure or number of chromosomes in the cells.
• 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 AML depend on the following:

• Age, general health, and number of white blood cells in the blood at diagnosis.
• Whether the AML was caused by previous anticancer treatment.
• The subtype of AML.
• Whether the disease has spread to the central nervous system (brain and spinal cord) or to other parts of the body.
• Whether the child has Down syndrome. Most children with AML and Down syndrome can be cured of their leukaemia.
• How well the leukaemia responds to initial treatment.
• Whether the AML is untreated or has recurred (come back) after being treated.

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 red blood cells, white blood cells, or platelets are.
• Whether the myelodysplastic syndrome is untreated or has recurred after treatment.

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

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

Stages of Childhood Acute Myeloid Leukaemia and Other Myeloid Malignancies

Key Points for This Section

• Once childhood AML has been diagnosed, tests are done to find out if the cancer has spread to other parts of the body.
• There is no standard staging system for childhood AML.

Once childhood 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 leukaemia (AML), the subtype of AML and whether the leukaemia 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 leukaemia 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 AML is described as untreated, in remission, or recurrent.

Untreated childhood AML

In untreated childhood AML, the disease is newly diagnosed. It has not been treated except to relieve symptoms such as fever, bleeding, or pain, and the following are true:

• The complete blood count is abnormal.
• More than 20% of the cells in the bone marrow are blasts (leukaemia cells).
• There are signs or symptoms of leukaemia.

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 (leukaemia cells).
• There are no signs or symptoms of leukaemia in the brain, spinal cord, or other parts of the body.

Recurrent Childhood Acute Myeloid Leukaemia and Juvenile Myelomonocytic Leukaemia

Recurrent childhood acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) are cancers that have recurred (come back) after they have been treated. The cancer may come back in the blood and bone marrow or in other parts of the body.

Treatment Option Overview

Key Points for This Section

• There are different types of treatment for children with AML, myelodysplastic syndromes, and JMML.
• Children with AML, myelodysplastic syndromes, and JMML should have their treatment planned by a team of doctors with expertise in treating childhood leukaemia and other diseases of the blood.
• The treatment of childhood AML usually has two phases.
• Five types of standard treatment are used for AML, myelodysplastic syndromes, and JMML.
o Chemotherapy
o Radiation therapy
o Stem cell transplantation
o Other drug therapy
o Watchful waiting

• Other types of treatment are being tested in clinical trials. These include the following:
o Biologic therapy

There are different types of treatment for children with AML, myelodysplastic syndromes, and JMML.

Different types of treatment are available for children with acute myeloid leukaemia (AML), myelodysplastic syndromes, and juvenile myelomonocytic leukaemia (JMML). 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's Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

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

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

• Haematologist.
• Medical oncologist.
• Paediatric surgeon.
• Radiation oncologist.
• Neurologist.
• Neuropathologist.
• Neuroradiologist.
• Paediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.

Regular follow-up exams are very important. Side effects may occur long after treatment has ended.

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 leukaemia cells in the blood and bone marrow. This puts the leukaemia into remission.
• Consolidation/intensification therapy: This is the second phase of therapy. It begins once the leukaemia is in remission. The purpose of postremission therapy is to kill any remaining leukaemia 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 leukaemia 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 leukaemia cells in the CNS and prevent the cancer from recurring (coming back). CNS sanctuary therapy is also called CNS prophylaxis.

Five types of standard treatment are used for AML, myelodysplastic syndromes, and JMML.

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.

Intrathecal chemotherapy may be used to treat childhood AML that has spread, or may spread, to the brain and spinal cord. When used to prevent cancer from spreading to the brain and spinal cord, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. Intrathecal chemotherapy is given in addition to chemotherapy by mouth or vein.

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

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 transplantation is a method 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 leukaemia cells, stop the leukaemia cells from dividing, or help the leukaemia cells mature into white blood cells. These drugs are used in the treatment of a subtype of AML called acute promyelocytic leukaemia.

Watchful waiting

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

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

Biologic therapy

Biologic therapy is a cancer 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 deliver 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's Web site.

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

Untreated Childhood Acute Myeloid Leukaemia, Myelodysplastic Syndromes, and Juvenile Myelomonocytic Leukaemia

Treatment of untreated childhood acute myeloid leukaemia (AML) depends on the subtype of AML and may include the following:

• Combination chemotherapy.
• Intrathecal chemotherapy with or without radiation therapy to the brain.
• All-trans retinoic acid (ATRA) plus chemotherapy.
• Arsenic trioxide therapy.
• A clinical trial of chemotherapy with or without arsenic trioxide therapy.

Standard treatment of newly diagnosed myelodysplastic syndromes may include the following:

• Stem cell transplantation.
• Combination chemotherapy.
• Watchful waiting.

Treatment of juvenile myelomonocytic leukaemia may include the following:

• Combination chemotherapy.
• Stem cell transplantation.
• A clinical trial of combination chemotherapy, other drugs, 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's Web site.
Childhood Acute Myeloid Leukaemia in Remission

Treatment of childhood acute myeloid leukaemia (AML) during the remission phase depends on the subtype of AML and may include the following:

• Combination chemotherapy.
• Stem cell transplantation.
• A clinical trial of chemotherapy and 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's Web site.
Recurrent Childhood Acute Myeloid Leukaemia

Treatment of recurrent childhood acute myeloid leukaemia (AML) depends on the subtype of AML and may include the following:

• Combination chemotherapy with or without stem cell transplantation.
• All-trans retinoic acid (ATRA) or arsenic trioxide therapy.
• A clinical trial of new anticancer drugs.
• A clinical trial of new biologic therapies.
• A clinical trial of stem cell transplantation using patient, matched or mismatched donor, or umbilical cord stem cells.