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 blood stem cells (immature cells) that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. The lymphoid stem cell develops into a white blood cell. The myeloid stem cell develops into one of three types of mature blood cells:
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 myeloid stem cells usually develop into a type of immature white blood cell called myeloblasts (or myeloid blasts). The myeloblasts, or leukemia cells, in AML are abnormal and 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.
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 around the age of 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.
In myelodysplastic syndromes (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 treatment for MDS depends on how much lower than normal the number of red blood cells, white blood cells, or platelets is. MDS may progress to AML.
The risk factors for developing childhood AML, childhood CML, JMML, TMD 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 doesnít mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Possible risk factors for childhood AML, childhood CML, JMML, TMD, and MDS include the following:
Possible signs of childhood AML, childhood CML, JMML, or MDS include fever, feeling tired, and easy bleeding or bruising.
These and other symptoms may be caused by childhood AML, childhood CML, JMML, or MDS. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
The symptoms of TMD may include the following:
Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood AML, childhood CML, JMML, TMD, and MDS.
The following tests and procedures may be used:
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 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 prognosis (chance of recovery) and treatment options for MDS depend on the following:
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:
There are three ways that cancer spreads in the body.
When cancer cells spread outside the blood, a solid tumor may form. This process is called metastasis. The three ways that cancer cells spread in the body are:
The new (metastatic) tumor is the same type of cancer as the primary cancer. For example, if leukemia cells spread to the brain, the cancer cells in the brain are actually leukemia cells. The disease is metastatic leukemia, not brain cancer.
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:
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 (MDS).
Different types of treatment are available for children with AML, CML, JMML, TMD, or MDS. 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. Some clinical trials are open only to patients who have not started treatment.
Children with AML, CML, JMML, TMD, or MDS should have their treatment planned by a team of health care providers who are experts in treating childhood leukemia and other diseases of the blood.
Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other health care providers who are experts in treating children with leukemia and who specialize in certain areas of medicine. These may include the following specialists:
Some cancer treatments cause side effects months or years after treatment has ended.
Regular follow-up exams are very important. Some cancer treatments cause side effects that continue or appear months or years after cancer treatment has ended. These are called late effects. Late effects of cancer treatment may include:
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 effects cancer treatment can have on their child.
The treatment of childhood AML usually has two phases.
The treatment of childhood AML is done in phases:
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 MDS.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them 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. Anticancer drugs 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, an anticancer drug is injected into the fluid-filled space to kill leukemia cells that may have spread there. This is called intrathecal chemotherapy.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. 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 is closely monitoring a patientís condition without giving any treatment until symptoms appear or change. It is sometimes used to treat MDS or TMD.
Supportive care is given to lessen the problems caused by the disease or its treatment. Supportive care may include the following:
New types of treatment are being tested in clinical trials
Biologic therapy is a treatment that uses the patientís immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the bodyís 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.
Natural killer (NK) cells are white blood cells that can kill tumor cells. These may be taken from a donor and given to the patient by infusion to help kill leukemia cells.
Patients may want to think about taking part in a clinical trial
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
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 may include the following:
Treatment of newly diagnosed childhood acute leukemia with a granulocytic sarcoma (chloroma) may include chemotherapy with or without radiation therapy.
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:
Recurrent Childhood Acute Myeloid Leukemia
Treatment of recurrent childhood acute myeloid leukemia may include the following:
Treatment of recurrent acute promyelocytic leukemia may include all-trans retinoic acid or arsenic trioxide therapy.
Acute Promyelocytic Leukemia
Treatment of acute promyelocytic leukemia may include the following:
Supportive care treatments are used to manage problems caused by the disease, such as infection, bleeding, and anemia.
Children with Down Syndrome and AML
Treatment of acute myeloid leukemia in children who have Down syndrome may include the following:
Childhood Chronic Myelogenous Leukemia
Treatment for childhood chronic myelogenous leukemia may include the following:
Juvenile Myelomonocytic Leukemia
Treatment of juvenile myelomonocytic leukemia is usually stem cell transplant.
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:
Treatment of myelodysplastic syndromes (MDS) may include the following:
Supportive care treatments are used to manage problems caused by the disease, such as infection, bleeding, and anemia.
If the MDS progresses to acute myeloid leukemia (AML), treatment will be the same as treatment for the newly diagnosed patient with AML.
Source: National Institutes of Health; National Cancer Institute