Leukemia - Acute Myeloid - AML - Childhood

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What is Leukemia - Acute Myeloid - Childhood ?

Leukemia is a cancer of the blood. It begins when normal blood cells change and grow uncontrollably. Acute myeloid leukemia (AML) is a type of leukemia that is a cancer of the blood-forming tissue in the bone marrow. AML may also be called acute nonlymphocytic leukemia or acute myelogenous leukemia.

About bone marrow and blood cells

Bone marrow is the spongy, red tissue in the inner part of the large bones and is where a person’s blood cells are made. Normal immature blood cells are called blasts. Blasts mature into one of three different types of blood cells:

White blood cells, which fight infection in the body

Red blood cells, which carry oxygen and other nutrients throughout the body

Platelets, which help the blood to clot

About AML

In AML, the bone marrow makes many abnormal cancerous cells, also called blasts or myeloblasts because they look similar to normal immature blast cells. Instead of becoming healthy mature blood cells, cancerous cells divide rapidly and uncontrollably. The cancerous cells are unable to mature and work like normal blast cells, and they do not die easily. Eventually, these myeloblasts fill up the bone marrow, preventing healthy cells from being made, and then build up 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 develop leukemia. This section is about AML that occurs in children, sometimes called pediatric AML. 

Symptoms and Signs

Children with AML may experience the following symptoms or signs. 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 or sign 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 making fewer normal blood cells and the buildup of cancerous AML cells. Often a child with AML will have one or more of the following symptoms:

Fever

Chills

Aching bones and joints

Swollen lymph nodes

Bleeding and bruising easily

Paleness

Fatigue

The doctor will ask you questions about the symptoms your child is experiencing to help find out the cause of the problem, called a diagnosis. This may include how long your child has been experiencing the symptom(s) and how often.

If cancer is diagnosed, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your child’s health care team about symptoms your child experiences, including any new symptoms or a change in symptoms.

Risk Factors

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often 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 four years of life. However, the reasons for this increased risk are not well understood.

AML occurs more 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.

Diagnosis

Doctors use many tests to diagnose leukemia. Some tests may also help the doctor choose the treatment that may be the most effective. This list describes options for diagnosing this type of cancer, and not all tests listed will be used for every child. Your child’s doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of cancer suspected

Signs and symptoms

Previous test results

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 (called differential count) are blood tests done to count the number of each type of blood cell under a microscope and to check 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, a sample of bone marrow is removed from the child’s hip with a needle and examined under a microscope. The child’s skin in that area will be numbed with medication beforehand, and other types of anesthesia (medication to block the awareness of pain) may be used. From this test, the doctor can find out whether the child has leukemia and, if so, what type of leukemia it is.

Molecular and genetic testing. Your doctor may recommend running laboratory tests to identify specific genes, proteins, and other factors involved in the leukemia. Examining the genes in the leukemia cells is important because AML can be caused by a buildup of mistakes (also called mutations) in the genes of a cell in the body. Identifying these mistakes helps diagnose the specific subtype of AML and choose treatment options. In addition, they can also be used to monitor how well treatment is working. Listed below are the more common molecular or genetic tests used for AML.

Cytochemical and immunohistochemical tests are laboratory tests that are used to find out the exact subtype of AML. In cytochemical tests, a special dye is used that stains the different types of leukemia cells differently based on the chemicals in the cells. For AML, immunohistochemical tests and a test called flow cytometry are used to find markers on the surface of the leukemia cells. The different subtypes of leukemia have different and unique combinations of cell surface markers.

Cytogenetics is a way to look at cell’s chromosomes (long strands of genes) through a microscope to analyze the number, size, shape, and the arrangement of the chromosomes to find genetic changes in the leukemia cells. Sometimes, a chromosome breaks off and reattaches to another chromosome, which is called a translocation. Other times, part of a chromosome is missing, called a deletion. A chromosome can also be made more than once, most often called a trisomy. Some subtypes of leukemia are caused by chromosome translocations, deletions, or trisomies. Knowing if there are certain translocations may help doctors determine the AML subtype and plan the best treatment. Flourescence-in-situ-hybridization (FISH) is a way to detect chromosome changes in cancer cells and is being used more often to help diagnose and determine the subtype of leukemia. This test is done on tissue removed during a biopsy or aspiration (see above).

The molecular genetics of leukemia cells can also be used to help find out if a person needs more or less chemotherapy and/or stem cell transplantation . The goal of this type of testing is to look for very small genetic mutations, called sub-microscopic mutations. People who have the Flt3 (pronounced flit 3) genetic mutation, called an internal tandem duplication (ITD), and specifically those with the mutation on both versions of the gene, have a high risk that the cancer will come back after treatment. For children with this type of AML, the use of stem cell transplantation may lengthen their lives when used after the first complete remission. There are also new drugs being tested that target Flt3-ITD positive cells to find out if the drugs can better treat the leukemia. Most recently, research has shown that children with two leukemia cell gene mutations called nucleophosmin-1 (NPM1) and CEBPα have a better prognosis (chance of recovery) than those without these mutations. If a child has these mutations, the doctor may recommend chemotherapy without stem cell transplantation.

Recently, highly advanced tools that can look at a person’s entire genetic make-up, called whole genome testing and whole exome testing, have been developed. These methods of testing are still early but have been used to look for genetic mistakes that can lead to cancer. However, these tests are still generally only available in research studies where they are being used to find out if using these tests improves diagnosis, treatment, and cure.

After these diagnostic tests are done, your child’s doctor will review all of the results with you. If the diagnosis is AML, these results also help the doctor describe the cancer and determine the subtype.

Subtypes

AML blasts are classified based on how much they look like normal immature bone marrow blast cells, and more recently, on the genetic testing of the leukemia cells. 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). Now, a new method of subtyping AML is used that takes into consideration the cytogenetic causes of AML. This is called the World Health Organization (WHO) 2008 classification. These subtypes include:

1) Acute myeloid leukemia with recurrent genetic abnormalities

a) AML with t(8;21)(q22;q22); RUNX1-RUNX1T1

b) AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11

c) Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA

d) AML with t(9;11)(p22;q23); MLLT3-MLL

e) AML with t(6;9)(p23;q34); DEK-NUP214

f) AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

g) AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1

h) AML with mutated NPM1

i) AML with mutated CEBPα

 2) Acute myeloid leukemia with myelodysplasia-related changes

 3) Therapy-related myeloid neoplasms

 4)  Acute myeloid leukemia, not otherwise specified

 a) AML with minimal differentiation

 b) AML without maturation

 c) AML with maturation

 d) Acute myelomonocytic leukemia

 e) Acute monoblastic/monocytic leukemia

 f) Acute erythroid leukemia

(i) Pure erythroid leukemia

(ii) Erythroleukemia, erythroid/myeloid

 g) Acute megakaryoblastic leukemia

 h) Acute basophilic leukemia

 i) Acute panmyelosis with myelofibrosis

5) Myeloid sarcoma

6) Myeloid proliferations related to Down syndrome

a) Transient abnormal myelopoiesis

b) Myeloid leukemia associated with Down syndrome

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