Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML)

Overview

Acute myeloid leukemia (AML) is a rare cancer that affects your bone marrow and blood. It typically happens when certain genes or chromosomes mutate (change). AML usually affects people age 60 and older, but it can also affect younger adults and children. Acute myeloid leukemia is an aggressive cancer that can be life-threatening. Newer treatments are helping people to live longer with AML.

Type of Acute Myeloid Leukemia

There are several AML subtypes. They all affect your blood cell levels, but different types of AML cause different symptoms and respond to treatment in different ways.

Medical pathologists determine AML subtypes by examining cancerous cells under a microscope. They also look for changes in your chromosomes and mutations in certain genes that help manage how cells grow and function.

AML subtypes include:

Myeloid leukemia: Cancer in cells that produce neutrophils, a white blood cell. Most people with AML have the myeloid leukemia subtype.

Acute monocytic leukemia (AML-M5): Cancer in cells that produce monocytes, a white blood cell.

Acute megakaryocytic leukemia (AMLK): Cancer in cells that produce red blood cells or platelets.

Acute promyelocytic leukemia (APL): Cancer in promyelocytes (immature white blood cells) that keeps these cells from developing.

Symptoms

Early on, AML symptoms may feel like you have a cold or flu that won’t go away. Acute myeloid leukemia is aggressive. That means you quickly develop new and more noticeable symptoms. Later symptoms include:

Dizziness.

Easy bruising or bleeding, including frequent nosebleeds and bleeding gums.

Fatigue.

Feeling cold.

Fever.

Night sweats.

Frequent infections or infections that don’t go away.

Headaches.

Loss of appetite.

Unexplained weight loss.

Pale skin.

Shortness of breath (dyspnea).

Swollen lymph nodes.

Weakness.

Bone, back or abdominal pain.

Tiny red spots on your skin (petechiae).

Wounds or sores that don’t go away.

Causes

Experts aren’t sure what causes acute myeloid leukemia. They do know the condition happens when certain genes or chromosomes mutate (change), creating abnormal blood cells. These genetic changes may happen:

During your lifetime when something changes your DNA.

If you inherited a genetic disorder that increases your risk of developing AML.

If there was a change in certain genes in your biological parents’ sperm or egg.

How do genetic changes cause acute myeloid leukemia?

To understand how genetic changes cause AML, it may help to know more about your bone marrow and blood cells. Your bone marrow is soft, spongy tissue in the center of most of your bones. It makes:

Stem cells (immature cells) that mature into red blood cells that carry oxygen.

White blood cells that protect against infection.

Platelets, which help your blood to clot.

Normally your bone marrow works like an efficient production line, consistently making the exact number of blood cells and platelets that your body needs to function. In AML, however, your bone marrow produces abnormal myeloid cells called myeloid blasts or myeloblasts.

Myeloid blasts don’t act like normal blood cells. Normal cells follow genetic directions that tell them when and how quickly they should multiply and grow. As cells get older, they die to make room in your bone marrow for new cells. Myeloid blasts don’t follow directions. They multiply uncontrollably and they don’t die. The continuous flow of myeloid blasts in your bone marrow means less room for healthy blood cells. Since there’s no room, your bone marrow stops making blood cells. Without new healthy blood cells, your body doesn’t have what it needs to function.

Moreover, as the myeloid blasts keep on multiplying, they begin to spill out of your bone marrow into your bloodstream. Once in your bloodstream, the myeloid cells travel to other parts of your body, including your central nervous system, brain and spinal cord.

Risk Factor

While experts don’t know exactly what triggers the genetic mutations that cause AML, they do know about risk factors that increase your chance of developing the disease. (When you think about risk factors, it’s important to remember risk factors don’t mean you’ll get sick.) Acute myeloid leukemia risk factors include:

Age. About half of all people with AML are 65 or older when they’re diagnosed. Again, AML typically affects adults but it can affect children.

Smoking, including exposure to secondhand smoke.

Cancer treatments, including chemotherapy and radiation therapy.

Long-term exposure to chemical carcinogens such as benzene and formaldehyde.

High-dose radiation exposure from a nuclear reactor accident or atomic bomb.

Certain inherited (genetic) disorders.

Other bone marrow disorders.

What genetic disorders increase the risk of developing AML?

Researchers know some inherited genetic mutations increase people’s risk for developing AML, including:

Down syndrome.

Ataxia telangiectasia.

Li-Fraumeni syndrome.

Klinefelter syndrome.

Fanconi anemia.

Wiskott-Aldrich syndrome, which affects platelet production.

Bloom syndrome.

Familial Platelet Disorder syndrome, which affects platelet disorder.

What bone marrow diseases increase the risk of developing AML?

Some people who have myeloproliferative neoplasms (myeloproliferative disorders) may develop acute myeloid leukemia. (Myelo means bone marrow. Proliferative means too many.) People with the following disorders may also develop ML:

Polycythemia vera.

Myelofibrosis.

Thrombocytosis.

Myelodysplastic syndrome.

Aplastic anemia.

Complication

Early on, acute myeloid leukemia affects the number of healthy red and white blood cells and platelets that you have. If you don’t have enough healthy blood cells and platelets, you may develop the following conditions:

Anemia.

Thrombocytopenia.

Pancytopenia (low blood cell and platelet levels).

Diagnosis

Healthcare providers use several tests to diagnose AML, including genetic tests to identify AML type. Providers typically start with a physical examination. They check for bruises, bleeding or infection. They check for enlarged (swollen) organs, specifically your liver, spleen and lymph nodes.

You may have one or more of these tests:

Complete blood count (CBC).

Peripheral blood smear.

Bone marrow biopsy.

Spinal tap.

Medical pathologists do genetic tests to identify AML type. They may examine certain chromosomes or genes to see if they’ve mutated or changed. Knowing AML type helps providers decide which treatment is most likely to eliminate AML. Specific tests may include:

Immunohistochemistry, which involves staining cells viewed under a microscope. The dye stains cells differently based on the cells’ chemicals.

Flow cytometry.

Karyotype test.

Fluorescence-in-situ-hybridization (FISH), which detects chromosome changes.

Treatment

Treatments may include chemotherapy, targeted therapy (including monoclonal antibody therapy) or allogeneic stem cell transplantation. Adults and children have the same treatment options. The goal is to put AML into complete remission. In AML, complete remission means tests show your blood counts are normal. It also means pathologists don’t see cancerous cells when they examine your bone marrow sample under a microscope.

Chemotherapy for AML

There are three phases to chemotherapy for AML — induction, consolidation and maintenance.

Remission induction therapy

This is the first step toward complete remission of AML. Treatment usually happens over several days. Some people need two rounds of induction therapy before AML is in complete remission. Providers may use the following chemotherapies in remission induction therapy:

Cytarabine (Cytosar-U®).

Daunorubicin (Cerubidine®).

Idarubicin (Idamycin®).

Azacitidine (Vidaza®).

Decitabine (Dacogen®.

Glasdegib (Daurismo®).

Venetoclax (Venclexta®, Venclyxto®).

Experts estimate induction therapy results in remission for:

More than 60% of children and teens.

About 75% of adults age 60 and younger.

About 50% of people over age 60.

Consolidation therapy

Consolidation therapy kills any remaining cancerous cells. It lowers the risk of cancer recurrence (coming back). Most people receive high-dose cytarabine (Ara-C) or HiDAC five days each month for three or four months.

Maintenance therapy

Often, consolidation therapy eliminates AML. In some cases, however, providers may recommend ongoing treatment using low doses of chemotherapy. Maintenance therapy may continue for months or years. Chemotherapy drugs for maintenance therapy may include:

Azacitidine (Vidaza®).

Decitabine (Dacogen®)

Midostaurin (Rydapt®).

Targeted therapy

Like its name suggests, this treatment targets specific genetic mutations in cancerous cells. Targeting the mutations keeps cancerous cells from growing. Monoclonal antibody therapy is a form of targeted therapy. Providers may use targeted therapy to treat AML that’s come back or hasn’t responded to chemotherapy:

Providers may use chemotherapy drugs midostaurin (Rydapt®) or gilteritinib (Xospata®) to treat people who have AML with a FTL3 gene mutation. About 25% to 30% of people with AML carry this mutation.

They may use enasidenib (IDHIFA®) or ivosidenib (Tibsovo®) to treat people who have AML caused by mutation of their X gene.

Allogeneic stem cell transplantation

Allogeneic stem cell transplantation uses stem cells from related or unrelated donors. Providers may obtain stem cells from bone marrow, peripheral blood or cord blood (blood collected from umbilical cords after birth).

Treatment complications or side effects

All cancer treatments have side effects. In AML, stem cell transplantation has the most serious side effects. Chemotherapy may cause myelosuppression, when you don’t have the normal number of blood cells and platelets. Targeted therapy side effects vary based on the specific drugs used.

Understanding side effects is an important part of knowing how cancer treatment will affect your daily life. Your healthcare provider is your best resource of information about specific treatment side effects. Some people may benefit from palliative care to help manage side effects.

Type of Doctor Department : A hematologist-oncologist