Shall we talk about this serious blood cancer, Acute Myeloid Leukemia (AML)?

Do you have a cold that doesn't go away after a few days? Or do you just feel tired and lethargic? Sometimes, small things like this can be hiding something big. Today we're going to talk about a disease that's a little serious, but it's very important to be aware of. That's acute myeloid leukemia, or AML for short.

What is AML?

Simply put, Acute Myeloid Leukemia (AML) is a type of cancer that affects your bone marrow and blood. It is a rare but serious disease. It is usually caused by a mutation in one of your genes or chromosomes. It is most common in people over the age of 60. However, it can also affect young people and children. AML is a rapidly spreading, life-threatening cancer. Fortunately, new treatments have allowed many people to live longer with the disease.

Are there different types of AML?

Yes, there are several different subtypes of AML. Each of these types affects the number of cells in your blood. However, each type can cause different symptoms and respond differently to treatment.

Doctors diagnose these subtypes of AML by examining the cancer cells under a microscope. They also look for changes in your chromosomes and mutations in certain genes that control cell growth.

Here are some of the main subtypes of AML:

• Myeloid leukemia: This is the most common type of AML. It develops as a cancer of the cells that produce neutrophils, a type of white blood cell.
• Acute monocytic leukemia (AML-M5): This develops in cells that produce a type of white blood cell called monocytes.
• Acute megakaryocytic leukemia (AMLK): This is a cancer of the cells that produce red blood cells or platelets.
• Acute promyelocytic leukemia (APL): In this, a type of immature white blood cell called promyelocytes does not develop properly and becomes cancerous cells.

How common is AML?

AML is actually a relatively rare disease. On average, about 4 out of 100,000 adults develop the disease each year. Also, it is reported that about 1,160 children are diagnosed with AML each year.

What are the symptoms of AML?

In the early stages, AML symptoms may feel like you have a bad cold or flu that has been going on for a few days. But AML is a very aggressive cancer. This means that you will quickly start to develop new, more obvious symptoms. Later, you may notice symptoms like:

• Constant feeling of dizziness.
• Things like bruising easily, frequent nosebleeds, and bleeding gums when brushing your teeth.
• Feeling of unbearable fatigue.
• Feeling cold.
• Fever.
• Night sweats.
• Frequent infections occur, or infections that do occur take a long time to heal.
• Headaches.
• The food is tasteless.
• Being thin for no reason.
• Pale skin.
• Difficulty breathing (dyspnea).
• Swollen lymph nodes.
• Feeling of weakness.
• Pain in the bones, back, or stomach.
• Small red spots on the skin (petechiae).
• Wounds take time to heal.

What are the causes of AML?

Experts still don't know exactly what causes AML. But they do know that the condition occurs when certain genes or chromosomes in our bodies change (mutate), causing abnormal blood cells to form. These genetic changes can include:

• Something has affected your DNA during your lifetime.
• If you have a genetic disorder that is passed down through generations and increases your risk of developing AML.
• Because of a change in some of the genes in your parents' sperm or eggs.

How do genetic changes cause AML?

To understand how these genetic changes can lead to AML, it's helpful to know a little about your bone marrow and blood cells. Your bone marrow is the soft, spongy tissue in the center of most of your bones. It's made up of:

• Stem cells are formed. These are the cells that later become red blood cells that carry oxygen, white blood cells that protect against infection, and platelets that help blood clot.

Normally, your bone marrow works like an efficient production line, making just the right amount of blood cells and platelets for your body. But in someone with AML, the bone marrow starts producing abnormal myeloid cells called myeloid blasts or myeloblasts.

These myeloid blast cells don't behave like normal blood cells. Normal cells get instructions from their genes about when and how fast they should divide and grow. When the cells get old, they die to make way for new cells in the bone marrow. But myeloid blast cells don't follow these instructions. They divide uncontrollably and don't die. As myeloid blast cells continue to fill the bone marrow, there's no room for healthy blood cells. Because there's no room, the bone marrow stops making healthy blood cells. Without new healthy blood cells, the body doesn't get the things it needs to function properly.

Furthermore, as these myeloid blast cells continue to divide, they move out of the bone marrow and into the bloodstream. Once in the bloodstream, these myeloid cells travel to other parts of the body, including your central nervous system, brain, and spinal cord.

What are the risk factors for developing AML?

Although experts don't know exactly what causes the genetic mutations that lead to AML, they do know of some things (risk factors) that increase your risk of developing the disease. (When we think of risk factors, it's important to remember that having a risk factor doesn't mean you'll get the disease. ) Risk factors for AML include:

• Age: About half of people who develop AML are 65 years or older when diagnosed. However, as mentioned earlier, AML most often occurs in adults, but it can also occur in children.
• Smoking: This includes inhaling secondhand smoke.
• Cancer treatments: Things like chemotherapy and radiation therapy.
• Long-term exposure to certain chemical carcinogens: Examples include things like benzene and formaldehyde.
• Exposure to high doses of radiation from a nuclear reactor accident or atomic bomb.
• Some inherited genetic disorders.
• Other bone marrow disorders.

What genetic diseases increase the risk of AML?

Researchers have found that certain inherited genetic mutations increase the risk of developing AML. Some of these include:

• Down syndrome
• Ataxia telangiectasia
• Li-Fraumeni syndrome
• Klinefelter syndrome
• Fanconi anemia
• Wiskott-Aldrich syndrome - This affects platelet production.
• Bloom syndrome
• Familial Platelet Disorder syndrome - This is also a platelet-related disease.

What bone marrow diseases increase the risk of AML?

Some people with myeloproliferative neoplasms, or myeloproliferative disorders, can develop acute myeloid leukemia. (Myelo means bone marrow. Proliferative means to grow too much.) People with the following conditions are also at higher risk of developing AML:

• Polycythemia vera
• Myelofibrosis
• Thrombocytosis
• Myelodysplastic syndrome
• Aplastic anemia

What are the possible complications of AML?

In its early stages, acute myeloid leukemia affects the number of healthy red blood cells, white blood cells, and platelets in your body. If you don't have enough healthy blood cells and platelets, you may experience conditions like:

• Anemia - that means lack of blood.
• Thrombocytopenia - This means a lack of platelets.
• Pancytopenia - This means a decrease in all types of blood cells and platelets.

How is AML diagnosed? (Diagnosis)

Doctors use several tests to diagnose AML, including genetic tests to determine the exact type of AML. The first step is usually a physical exam. This includes checking for bruising, bleeding, and infection. They also check for swelling in organs such as the liver, spleen, and lymph nodes.

What tests are used to diagnose AML?

You may need to have one or more of these tests:

• Complete blood count (CBC)
• Peripheral blood smear - This involves taking a blood sample and looking at it under a microscope.
• Bone marrow biopsy - In this, a small sample of bone marrow is taken and examined.
• Spinal tap - This is sometimes done to check for cancer cells in the fluid around the spinal cord.

What are the genetic tests used to diagnose AML?

Medical pathologists perform genetic tests to determine the exact type of AML. They look for changes (mutations) in certain chromosomes or genes. Once the type of AML is known, it is easier for doctors to decide which treatments are most likely to cure the AML. Some of the specific tests that are done for this purpose are:

• Immunohistochemistry: In this, cells are stained and examined under a microscope. The staining method varies depending on the chemicals present in the cells.
• Flow cytometry.
• Karyotype test.
• Fluorescence-in-situ-hybridization (FISH): This can detect changes in chromosomes.

What are the treatments for AML?

Treatment options include chemotherapy, targeted therapy (including monoclonal antibody therapy), or allogeneic stem cell transplantation. The same treatment options are available for both adults and children. The main goal of treatment is to achieve complete remission of AML. In AML, a 'complete remission' means that your blood counts are normal on tests. This also means that doctors can't see any cancer cells when they look at a sample of your bone marrow under a microscope.

Chemotherapy for AML

There are three main phases of chemotherapy for AML - induction, consolidation, and maintenance.

Remission induction therapy

This is the first step in getting rid of AML completely. Treatment usually lasts for a few days. Some people may need two or more rounds of this initial treatment to get rid of AML completely. Doctors may use the following chemotherapy drugs for this initial treatment:

• Cytarabine (Cytosar-U®)
• Daunorubicin (Cerubidine®)
• Idarubicin (Idamycin®)
• Azacitidine (Vidaza®)
• Decitabine (Dacogen®)
• Glasdegib (Daurismo®)
• Venetoclax (Venclexta®, Venclyxto®)

According to experts, these initial treatments:

• More than 60% of children and young people recover.
• About 75% of adults aged 60 and under recover.
• About 50% of people over 60 years old recover.

Consolidation therapy

Consolidation therapy is used to kill any remaining cancer cells. This reduces the risk of the cancer coming back (recurrence). Most people are given high-dose cytarabine (Ara-C) or HiDAC for five days each month for three to four months.

Maintenance therapy

Most of the time, AML is cured with consolidation therapy. However, in some cases, doctors may recommend continuing chemotherapy at lower doses. Maintenance therapy may continue for months or years. Chemotherapy drugs used for maintenance therapy may include:

• Azacitidine (Vidaza®)
• Decitabine (Dacogen®)
• Midostaurin (Rydapt®)

Targeted therapy

As the name suggests, this treatment targets specific genetic mutations in cancer cells. By targeting these mutations, the cancer cells stop growing. Monoclonal antibody therapy is also a type of targeted therapy. Doctors may use targeted therapies to treat AML that has not responded to chemotherapy or that has come back:

• Doctors may use the chemotherapy drugs Midostaurin (Rydapt®) or Gilteritinib (Xospata®) to treat AML patients with the FTL3 gene mutation. This mutation is found in 25% to 30% of people with AML.
• Enasidenib (IDHIFA®) or Ivosidenib (Tibsovo®) can be used to treat people who have AML due to a mutation of their X gene.

Allogeneic stem cell transplantation

An allogeneic stem cell transplant uses stem cells from a related or unrelated donor. Doctors can obtain these stem cells from bone marrow, peripheral blood, or cord blood (blood collected from the umbilical cord after birth).

Treatment complications or side effects

Almost all cancer treatments have side effects. In AML, stem cell transplantation has the most serious side effects. Chemotherapy can cause a condition called myelosuppression, which means your body loses the normal number of blood cells and platelets. The side effects of targeted therapies vary depending on the drug used.

Understanding side effects is important to know how cancer treatment will affect your daily life. Your doctor is the best person to know about the specific side effects of your treatment. Some people may benefit from palliative care to help manage side effects.

Can AML be completely cured?

Currently, allogeneic stem cell transplantation is the only way to completely cure acute myeloid leukemia. Depending on your condition, your doctor may recommend a stem cell transplant as your first AML treatment. Or, if your AML comes back within 12 months, this treatment may be suggested. Unfortunately, not everyone is eligible for a stem cell transplant.

What is the prognosis of AML?

When talking about the prognosis of acute myeloid leukemia, there are two aspects. One is complete remission. The other is recurrence, which is when AML develops again.

• Overall, it is estimated that between 50% and 80% of people with acute myeloid leukemia will make a full recovery after treatment. Children and people under 60 are more likely to make a full recovery. This recovery can last for months or years.
• About 50% of people who recover completely will develop AML again. If this happens, doctors may recommend additional chemotherapy or a stem cell transplant. They may also suggest taking part in a clinical trial.

If you or your child has AML, ask your doctor about what you can expect.

What is the survival rate of AML patients?

Acute myeloid leukemia is a complex disease. Because there are several subtypes of AML, it is difficult to give an exact prognosis.

For example, the five-year survival rate for children under 15 is 67%. But some studies suggest that the five-year survival rate for children with the subtype APL is more than 80%. Age also plays a role. On average, 30% of adults with AML survive five years after diagnosis. Remember, AML usually develops in people who are 60 years old and older, and who may also have other health problems.

It's important to remember that these survival rates reflect the experience of large groups of people with AML. This data includes survival rates from 2012 to 2018, and there are now newer, more effective treatments for AML.

Many factors affect how long you will live with acute myeloid leukemia. This means that your doctors, who know your medical history and overall health, are the best people to know about this.

Can AML be prevented?

No, acute myeloid leukemia cannot be prevented. Although experts know that AML is caused by genetic mutations, they don't know what causes it. But they do know about the risk factors that can lead to AML. Here are some risk factors that you can change:

• Smoking: This includes second-hand smoke. If you smoke, try to quit. If you live or work with someone who smokes, try to limit the time you spend with them when they are smoking.
• Long-term exposure to certain carcinogenic chemicals: especially benzene and formaldehyde. If you work with these carcinogens, take all safety precautions, such as wearing protective clothing.

How do I take care of myself? (Self-care)

Living with a cancer that can come back is not easy. Joining cancer survivorship programs is one way you can take care of yourself. You may not be able to stop acute myeloid leukemia from coming back. But you can take steps to stay as healthy as possible, no matter what. Here are some suggestions:

• Acute myeloid leukemia treatment can affect your diet. You need to eat well to stay strong. If you have trouble eating, talk to a nutritionist.
• The side effects of AML treatment can be difficult to manage. If needed, talk to your doctor about palliative care.
• Cancer is a very stressful condition. Exercise can help you manage stress. But talk to your doctor before starting a new, strenuous exercise program.
• Cancer can make you feel lonely. AML is a rare disease. You may feel nervous about talking about your condition. If so, consider joining a support group.
• Acute myeloid leukemia can make you feel very tired. The treatments can sap your energy. Remember to get as much sleep as you need.

When should I see a doctor?

You will see your doctor regularly throughout your recovery, especially if you are receiving maintenance therapy. Your doctor will tell you what symptoms may be signs that your AML is coming back. This will help you know when to contact them for new or additional treatments.

What questions should I ask my doctor?

If you have AML, you may want to ask yourself these questions:

• What type of AML do I have?
• What are my treatment options?
• What are the risks and side effects of treatment?
• How do I manage the side effects of treatment?
• What follow-up care do I need after treatment?
• Should I watch out for signs of complications?
• Are there any clinical trials I should consider?

Finally, things to remember

Acute Myeloid Leukemia (AML) is a rare cancer that affects your bone marrow and blood. AML usually affects people over the age of 65, but it can also affect children and young adults. Thanks to new treatments, more people are now living with AML in remission after treatment. Although the cancer can come back, medical researchers are continuing to research ways to treat AML that comes back.

If you or your child has acute myeloid leukemia, you may feel as if you have been thrown from solid ground into an uncertain sea. You may wonder if treatment will bring you relief. If so, you may worry about how long that relief will last. Your doctors understand how you feel. They will be with you as you deal with the challenges of AML. So stay strong and don’t hesitate to get the help you need.

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