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Acute myeloid leukemia

Acute myeloid leukemia
Acute myeloid leukemia (AML) is one of the types of blood cancer that start from cells that normally develop into white blood cells other than lymphocytes. Acute myeloid leukemia is sometimes called acute myelogenous leukemia, acute non-lymphocytic leukemia or acute granulocytic leukemia. The term “Acute’’ simply means leukemia can progress quickly, and without treatment it is likely to be fatal within a few months although if treated in time, most cases of AML respond to treatment very well. To understand leukemia, it is important for one to know blood first.

Blood is a fluid flowing in our bodies and it is the one that usually conveys nutrients and oxygen. In the body blood is carried in specified tubes known as vessels (veins and arteries). Blood is pumped around your body by a muscular organ called heart. Blood is made up of blood cells carried in a clear fluid called plasma. Blood cells are mainly of three types, red blood cells, white blood cells and platelets.
• Red blood cells. These carry oxygen around the body
• White blood cells. These are responsible for fighting infections
• Platelets. These help in blood clotting.
All these blood cell types have a limited life span, hence they are continuously replaced. Most are made in the bone marrow, which is the spongy part in the center of the bones such as the skull, ribs, hip bones, shoulder blades and backbones (vertebrae). Since leukemia is a blood cancer that mainly involves white blood cells, it is important to have a bit more knowledge on white blood cells.

Types of white blood cells
• Lymphocytes. These are the cells responsible for fighting infections and they develop from stem cells known as lymphoblast. Lymphocytes are the cells that mainly make up lymphoid tissues, which are major part of the immune system. The two main types of lymphocytes are;
• B- Cell lymphocytes. These cells make antibodies that fight germs and other infections. These are also called B-Cells.
• T-Cell lymphocytes. These are responsible for destroying germs and they also trigger B-cell lymphocytes to produce antibodies
• Granulocytes. These are mature cells that are responsible for fighting infections. These cells develop from myeloblasts. They are known as granulocytes because they have granules that show up as spots under the microscope. Types of white blood cells known as granulocytes include; neutrophils, eosinophils and basophils. These three differ in color and size of granule.
• Monocytes. These develop from blood-forming monoblasts in the bone marrow. After sometime in the blood stream, monocytes will enter body tissues to become macrophages. Macrophages destroy germs but also they help lymphocytes recognize germs.

About leukemia
Leukemia is a term used to describe blood cancer. Leukemia originates from the term leucocytes meaning white blood cells. Leukemia begins in the bone marrow, the spongy part in the center of the bone where blood cells are produced.
Bone marrow contains stem cells. These are unspecialized blood cells that first develop into immature cells known as blast cells. Normally, the blast cells then become mature red or white blood cells or platelets and carry out their set functions but if the blasts fail to mature properly or if they are too many in the blood, it may also result into leukemia. There are two types of stem cells;
• Myeloid stem cells. This develop into myeloblast cells that further develop to form red blood cells, platelets and most forms of white blood cells.
• Lymphoid stem cells. This develop into lymphoblast cells which then becomes lymphocytes which are type of white blood cells.
Following failure to mature properly into normal blood cells, myeloblast cells will result in
to development of type of leukemia known as myeloid leukemia while lymphoblast cells will result into lymphoblastic leukemia. In leukemia, abnormal white blood cells grow out of control and multiply in such a way that they crowd the bone marrow. This affectsbone marrow’s ability to produce normal levels of other blood cells, hence affecting the way the rest of the body work.
As leukemia progresses, more abnormal blood cells and fewer normal blood cells are produced in the marrow. Those abnormal cells in the marrow will spill out into the blood stream and build up in the blood, which may spread to other parts of the body such as lymph nodes, lungs, liver, spleen and kidneys.

Risk factors of acute myeloid leukemia
When dealing with cancer, anything that increases your probability of developing cancer is called a risk factor. Risk factor only influence development of cancer but it does not directly cause cancer. Sometimes people with risk factors do not develop the disease while those with no risk factors do develop the disease. Knowing risk factors will help you live your life making some better healthy choices to reduce the risk. The risk factors for acute myeloidleukemia (ALM) include the following;
• Radiation exposures. Exposure to high levels of radiation increases chance for someone to develop leukemia. This include long term survivors of atomic bombs and victims of radiation accidents (high energy radiation) such as those working with radiations. Also, treatment of cancer by using radiations is said to increase someone`s chance of developing AML.
• Genetic conditions. There are some genetic conditions that are highly linked to development of leukemia. These conditions include, Down syndrome, neurofibromatosis, Klinefelter syndrome, ataxia-telangiectasia, li-fraumen syndrome, fanconi anemia and familial platelet disorder syndrome.
• Chemical exposure. Exposure to some chemicals such as benzene which is used in various places such as oil refining plants, rubber processing industries and shoe manufacturing industries, will increase the chance for developing leukemia at some point in life.
• Cigarette smoking. Cigarette smoke also contains benzene which is one of the chemicals linked to leukemia. Smokers have an increased risk of developing AML compared to non-smokers.
• Gender. Statistics shows that, number of men affected by AML is slightly higher compared to that of women.
• Bone marrow disorders. Some bone marrow (blood) disorders are linked to the development of AML. Those conditions include myelofibrosis, aplastic anemia, myelodysplastic syndrome and essential thrombosis.

Prevention of acute myeloid leukemia
To prevent something, you first need to know its cause. But since the specific cause of acute myeloid leukemia is still unknown, there is no way of completely preventing the development of this cancer.
In addition to that, many of the risk factors of AML cannot be changed, hence even reducing risk of developing this cancer becomes very difficult. The only known risk factor that can be changed is cigarette smoking, so by avoiding and quitting cigarette smoking, you will reduce your chance of developing AML as a result of smoking.

Early detection and screening of AML
When it comes to cancer, early detection normally provide better treatment outcome. When acute myeloid leukemia (AML) is found early, chances for better treatment outcome are very high. For most cancers, early detection has been greatly contributed by the presence of screening process.
Screening is the process of running some tests to someone with no symptoms of the disease with the intention of determining presence or absence of the disease. Unfortunately, currently there are no widely recommended screening tests for this leukemia (AML). In order to detect this type of leukemia at an early stage, it is recommended to report to the hospital immediately upon experiencing any possible signs or symptoms of leukemia.
For those known to have higher risk of developing AML including those with inherited genetic disorder like Downs syndrome, Klinefelters syndrome and those with bone marrow disorders, it is recommended they should have regular clinical checkups.

Signs and symptoms of acute myeloid leukemia
Those with AML normally experience the following signs and symptoms. But sometimes those changes are caused by medical condition that is not cancer, having clinical checkups upon experiencing any of those symptoms is strongly advised. Signs and symptoms of AML include the following;
• Fatigued
• Easily bruising and bleeding
• Fever
• Dizziness
• Blurred vision
• Persistent infections
• Shortness of breath
• Frequent or severe nosebleed
• Enlarged liver and spleen
• Unexpected weight loss
• Enlarged lymph nodes
• Headaches
• Nausea and vomiting

Diagnosis of acute lymphocytic leukemia
Following suspicion of acute myeloid leukemia, various tests are used to verify the suspicion, learn if the disease has spread to other organs of the body and some tests will help to determine prognosis of the disease. When running those diagnostic tests, the doctor will consider some of the factors including;
• Results of the previous tests
• General health condition
• Type of cancer suspected
The following are some of the diagnostic tests for acute myeloid leukemia (AML) although not everyone will need to go through all those tests during diagnosis.
• Medical history and physical examination. The doctor will review patient`s history for risk factors but also do some physical examinations to check if there is any enlarged lymph nodes (lymphadenopathy) and abdominal swelling which can be a result of enlarged liver (hepatomegaly) and spleen (spleenomegaly).
• Blood tests. Blood samples will be taken and checked in the laboratory for full blood count (FBC). The results will reveal whether the levels of blood cells are normal or not. Blood sample may also be used to find if the blood cells are normal or abnormal (leukemia cells).
• Bone marrow tests. If the blood test shows abnormalities in the number or appearance of the white blood cells, the doctor may take some bone marrow sample to check for signs of leukemia. There are two main procedures used in taking bone marrow samples for testing;
• Bone marrow aspiration. This involves the removal of a fluid sample by using a needle (fluid part of bone marrow).
• Bone marrow biopsy. This involves the removal of a small amount of solid tissue using a needle.
If the results from blood tests suggest presence of leukemia, bone marrow tests are advised to be done at the hospital where treatment will be given so as not to do these tests twice.
• Cytochemistry. This diagnostic test is used to find out the specific subtype of AML. During the test, cells are exposed to chemical stains (dyes) that react with onlysome types of leukemia cells and become colored. After the reaction, cells are viewed under microscope and the doctor will be able to know the exact type of cells that are present. Stains can also help distinguish AML cells from ALL cells.
• Immunophenotyping. This test is also known as flow cytometry. It uses a machine (flow cytometer) to look for certain markers or signals (antigens) on the surface of the cell. This test can indicate the subtype of AML you have.
• Genetic tests. These include cytogenetics and molecular tests. Genetic makeup of cancer cells is different to that of normal cells as cancer cells have some faults to their genetic makeup. The study of these gene changes is called cytogenetics or molecular tests. These tests are normally done before treatment starts.
• Lumbar puncture. Lumber puncture is a procedure in which a doctor uses a needle to take a sample of cerebral spinal fluid (CSF) from the spine for examining presence of cancer cells. AML has a tendency of spreading to the CSF, which is the fluid that flows around the brain and spinal cord, so by taking the CSF sample for tests will help reveal if the disease has spreads to the fluid or not.
• Imaging tests. Imaging tests like CT scan, MRI scan, chest X-ray and PET scan are used to determine if the disease has spread to other structures of the body such as lymph nodes, liver and spleen.

Classification of acute myeloid leukemia (AML)
There are various classification systems used when dealing with acute myeloid leukemia (AML) but FAB classification system is most preferred. FAB classification system stands for French-American-British classification system. It was established in the 1970s when group of French, American, and British leukemia experts divided AML into subtypes, M0 through M7.

French-American-British classification system (FAB)
FAB classify AML into subtypes basing on the type of cell from which the leukemia develops and how mature the cells are. This depend on the appearance of leukemia cells under microscope. The subtypes are as follows;
M0: Undifferentiated acute myeloblastic leukemia
M1: Acute myeloblastic leukemia with minimal maturation
M2: Acute myeloblastic leukemia with maturation
M3: Acute promyelocytic leukemia (APML)
M4: Acute myelomonocytic leukemia
M4 eos: Acute myelomonocytic leukemia with eosinophilia
M5a: Acute monocytic leukemia without differentiation (monoblastic)
M5b: Acute monocytic leukemia with differentiation
M6: Acute erythroid leukemia
M7: Acute megakaryoblastic leukemia.
From M0 to M5, cancer start from immature white blood cells while M6 and M7, cancer start from immature red blood cells and platelets respectively.
Treatment of acute myeloid leukemia
Following cancer diagnosis, the doctor will break the news and it is normally not very easy to accept that it is cancer. The doctor will be there to help the patient process the news and to help the patient in taking the next steps.
After the patient receives and processes the news that he/she has cancer, one of the most important steps that will follow is decision making. The doctor will present to the patient (relatives/parents/guardians) with all the possible treatment options and explain what they mean. Then with the help of the doctor, the patient (relatives/parents/guardian) will have to choose which treatment option is good depending on benefits of such option.
Despite all the information given by the doctor, sometimes the patient may still be unsatisfied with what he/she has been told. In such situation, the patient is free and advised to seek a second opinion. Second opinion is the opinion that the patient may seek from another specialist (doctor) regarding his/her health problem and in this case it is cancer. Second opinion may include confirmation of the diagnosis, more clarification on your primary doctor recommendations or even reassurances that all the options have been explored.
In addition to standard care treatment options, sometimes there are those new treatments or drugs or combination of treatments that have not been approved yet to be used as standard care treatments for a particular cancer (disease) but have shown some promising results that they may help. These type of treatments are called clinical trials.
If there are some clinical trials for your case, the doctor may present to the patient or the patient may ask if there are any clinical trials for the particular cancer case. Over the years, have improved treatments and led to better outcomes to people diagnosed with various diseases including cancer. If you have decided to take part in clinical trial, you can also withdraw at any time

Treatment options
Treatment of AML requires a team of doctors and other health care professionals. This team work together and it is called multidisciplinary team. Team may vary depending on the treatment option for a particular case. But generally multidisciplinary team for treatment of AML includes hematologist, medical oncologist, radiation oncologist and other health care professionals like oncology nurses and palliative care team. Treatment options of AML include the following;
Chemotherapy is an option that involve the use of drugs to destroy cancer cells or slow its growth. It is given by a specialized doctor known as medical oncologist or hematologist. Chemotherapy is normally given through injection into veins (intravenously) and rarely swallowed as pill or capsule.
Normally, chemotherapy schedule consists number of cycles given over a specific period of time. AML patients, normally receive several different drugs throughout their treatment.

Side effects of chemotherapy
Side effects of chemotherapy depends on type of drug used, dose given and periodic time by which the drug has been used. Some of the possible side effects of this treatment option include the following;
• Loss of hair
• Fatigue
• Mouth sores
• Nausea and/or vomiting
• Diarrhea
• Risk of infections
• Easily bruised and bleeding

Radiation therapy
Radiation therapy is an option that involve using high energy x-rays or other radiation particles to destroy cancer cells. It is a treatment option given by a specialized doctor known as radiation oncologist. Between the two types of radiation therapy, external beam radiation therapy (source outside the body) is the one that is used for management of AML and it is used when leukemia cells have spread to the brain or when aiming to shrink a myeloid sarcoma.
If stem cell transplantation is the treatment of choice, radiation therapy is sometimes given to the whole body (total body irradiation), before transplantation starts. The aim of giving radiation therapy before transplantation is to kill remaining cancer cells in the bone marrow and also weakening body immunity to prevent rejection of transplanted cells.
The treatment is usually given as multiple small doses over several days or weeks to maximize the effect of the radiotherapy and reduce side effects.

Side effects of radiation therapy
Side effects of radiation therapy will depend on the site of treatment and dose of radiations given. Some of the possible side effects of radiation therapy include the following;
• Mild skin reactions
• Loss of hair
• Feeling tired
• Upset stomach
• Loose bowel movement

Stem cell transplant
Stem cell transplantation is an option that involve replacing a patient`s bone marrow by highly specialized cells called hematopoietic stem cells. Bone marrow that contain cancer cells is destroyed first by using high dose of chemotherapy or radiation therapy, then replaced by healthy stem cells.
This treatment option is sometimes called bone marrow transplantation. These cells will mature into heathy bone marrow. Hematopoietic stem cells are blood forming cells in the bone marrow.
A transplant is normally done in several stages and the entire procedure, including recovery, can take months. There are two types of stem cell transplantation;
• Autologous stem cell transplantation. This involves the use of stem cells that were previously removed from the patient`s blood stream and later transplanted (rein fused) back into the body.
• Allogeneic transplantation. This involve the use of stem cells taken from another person (donor). The donor may be a family member or from a donor registry.
For treatment of AML, allogeneic stem cell transplantation is the one normally used.

Side effects of stem cell transplantation
Most of the side effects of this treatment option resemble to those of chemotherapy but with this treatment options the side effects may be a little bit severe. Some of those possible side effects include the following;
• Nausea and vomiting
• Hair loss
• Risk of infection
• Easily bruising and bleeding
• Fatigue.
Targeted therapy Targeted therapy is an option that involve targetingspecific molecules in the cancer cells using drugs. The drug will stop the growth and spread of cancer cells and at the same time limit harm to normal cells. Drugs for this kind of treatment work differently to that of normal chemotherapy drugs. The drugs for this option can sometimes help even when chemo isn’t, but they can also be used along with normal chemotherapy to help it work better. Some of the drugs for targeted therapy used in treatment of AML include Midostaurin and Enasidenib. These two drugs are taken as pill once a day.

Side effects of targeted therapy
Some of the possible side effects of targeted therapy include the following;
• Nausea and/or vomiting
• Mouth sores
• Muscle or bone pain
• Increased risk of infection
• Upper respiratory infection
• High blood sugar level
• Increased level of bilirubin
• Loss of appetite
• Diarrhea
• Bruising

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