What is Acute Myeloid Leukemia in Children?

Acute myeloid leukemia (AML) is the second most common blood cancer in children. AML affects certain cells in the bone marrow (myeloid cells). These cells ordinarily develop into normal, mature blood cells. In AML, these immature cells do not develop properly and become cancerous. The cells multiply rapidly, building up in the bone marrow and crowding out normal, healthy cells. They can spill into the bloodstream and travel throughout the body, disrupting the normal function of organs.

As many as 80 percent of children with AML go into remission after the standard course of treatment. For those who do not, a more intensive or personalized course of treatment may be needed. It is especially important that these patients receive care from specialists with extensive experience in diagnosing and treating AML.

Below are some terms to know as you learn more about AML.

• Bone marrow: The soft, spongy center of bones where blood cells are produced.
• White blood cells (sometimes called leukocytes): Responsible for fighting infection and disease in the body.
• Myeloblasts: Immature white blood cells that become cancerous when a person has AML. They are sometimes called “blasts.”
• Red blood cells: Cells that carry oxygen to the body’s tissues.
• Platelets: An element in the blood that assists with clotting.

What causes AML?

Doctors do not know exactly what causes AML, but certain circumstances may increase a child’s risk of getting it. These include:

• Undergoing chemotherapy or radiation therapy for a different type of cancer
• Having another condition of the bone marrow that may evolve into AML
• Having certain inherited or acquired chromosome disorders

Most children who get AML do not have a family history of the disease. However, having a parent or sibling (especially an identical twin) with AML can be linked with an increased risk of getting AML.

What are the signs and symptoms of AML?

The early symptoms of AML occur as cancerous cells fill up the bone marrow and crowd out normal blood cells. This can result in high white blood cell counts and low red blood cell and platelet counts. Symptoms include:

• Fever/infections
• Fatigue and weakness
• Pale appearance
• Aches and pains in the bones
• Easy bruising or bleeding, such as nosebleeds or heavy menstrual periods
• A swollen belly (from an enlarged liver and spleen)
• Tumors in the skin or gums

With AML, these symptoms usually occur over a number of days or weeks. Many are similar to those of the flu. But if a child has several of these symptoms at once, it may be cause for concern.

How is AML diagnosed?

If the doctor suspects leukemia, the first step is to do a physical exam and a blood test. Additional tests help the medical team make a more detailed diagnosis and develop a personalized treatment plan.

Treatment for AML begins as soon as possible, usually within a few days of the initial blood work. Care team members will make adjustments as they see how the cancer responds to treatment. They also will treat any associated symptoms, such as fever and infections, anemia or risk of bleeding.

What are the different stages of AML?

AML tends to spread very quickly throughout the body, so doctors do not “stage” it as they do other types of cancer. However, they do characterize it in the following ways.

• Newly diagnosed: The child has never been diagnosed with AML before.
• Central nervous system (CNS) positive or negative: If blasts are seen in the spinal fluid, the AML is described as CNS positive. If the spinal fluid is not involved, the AML is CNS negative. Additional chemotherapy is directly administered into the spinal fluid to treat CNS-positive AML.
• In remission: The child has been treated successfully for AML; there is no sign of cancer in the body.
• Recurrent or relapsed: The child has received treatment for AML, and the disease has returned.
• Refractory: Treatment for AML did not eliminate the cancer, and the disease is still active.

Patients who are being treated for AML usually are hospitalized for the majority of the time they are undergoing treatment. This is because the drugs they receive affect healthy blood cells as well as cancer cells. During treatment, patients are at risk for getting a life-threatening infection and need to be monitored closely by the care team.

What is the standard treatment for AML?

Most children with AML respond well to a standard initial course of treatment, which occurs in two phases. The first phase is called induction. It is designed to kill as many cancer cells as possible using chemotherapy. The first “block” of induction treatment involves a 10-day course of chemotherapy, followed by four to six weeks of recovery. The care team will perform tests during the recovery period to see how well the treatment plan is working. The patient then will undergo a second induction block of chemo, followed by another four to six weeks of recovery.

If the leukemia can no longer be detected at the end of these two induction blocks, the patient is in remission, and phase two of treatment − intensification, or consolidation − begins. This is designed to deepen the remission and eliminate any undetectable leukemia cells and secure long-term survival. It involves two or three more blocks of chemotherapy.

These two phases of treatment take about six months total. About 80-90 percent of children achieve remission after the induction blocks of treatment. However, overall survival remains about 60-70 percent, since some children later develop relapse of the leukemia. Therefore, patients will continue to see the care team on a regular basis for follow-up and close observation.

How do doctors treat AML that doesn’t respond to standard treatment?

If a child has refractory (treatment-resistant) AML, or the AML returns after a period of remission, the care team may recommend a stem cell transplant (sometimes called a bone marrow transplant). This involves taking healthy stem cells from a donor and transplanting them into the child’s bloodstream. These fresh stem cells make their way to the bone marrow and start producing normal white blood cells, red blood cells and platelets.

Prior to transplant, the care team will design an intense course of therapy to destroy the cancer cells in the bone marrow. This process is called “conditioning,” and it helps make room in the patient's bone marrow for new blood stem cells to grow, helps prevent the patient's body from rejecting the transplanted cells, and helps kill any cancer cells that are in the body. Conditioning regimens can include:

• Conventional chemotherapy drugs
• Novel (experimental) chemotherapy drugs
• Drugs which may alter the genes in AML cells

If conditioning is successful, the stem cell transplant can proceed. Stem cell transplant specialists at Cincinnati Children’s use novel approaches to improve the effectiveness and safety of stem cell transplantation.

Stem cell transplant is often successful, but not always. Sometimes, even intensive conditioning cannot kill the cancer cells, and the leukemia returns. In other situations, complications arise and the stem cell transplant cannot take place, or the donor cells fail to engraft.

When leukemia relapses after transplant, or when life-threatening complications occur, the care team talks to families about next steps. Additional treatment options may be available in some situations, but in others, treatment may focus on pain control or improving the child’s quality of life, rather than continuing to seek a cure.

What Role Does Research Take in Acute Myeloid Leukemia Treatment?

Survival rates for children with AML are dramatically higher now than they were decades ago. The main reason for this encouraging trend is laboratory and clinical research, which helps scientists develop new, more effective and safer treatments.

Cincinnati Children’s offers several clinical trials for patients with AML, some of which are sponsored by national research groups and others that were designed by our own cancer specialists. The hope is that children who participate in clinical research at Cincinnati Children’s will benefit personally. Even if they do not, they are part of the “bigger picture” as researchers continue their quest for more effective therapies in the treatment of AML.

What is the long-term outlook for people with AML?

A child’s long-term prognosis after being diagnosed with AML depends on:

• How well the cancer responds to treatment
• The unique genetics and biology of the leukemia
• How the child tolerates specific medications, procedures or therapies
• New developments in treatment

Overall, between 60 percent and 70 percent of children treated for AML will be long-term survivors. For some specific types of AML, the long-term survival rate is higher than 80 percent.

Patients who achieve long-term remission must receive consistent follow-up care for the rest of their lives. In addition to watching for signs that the cancer has returned, this type of care ensures that any late effects from cancer treatment are addressed promptly.