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Acute Myeloid Leukemia 

Acute myeloid leukemia (AML) is a disease that can progress very rapidly. In a short time, there may be differences in blood values ​​and symptoms. The treatment of acute myeloid leukemia (AML), which manifests itself with symptoms such as sudden onset of weakness, fatigue, infection, cough, bone pain, constipation, nausea and vomiting, requires long-term and patience. The primary goal in the treatment of acute myeloid leukemia (AML) is to reduce the rate of leukemia cells (blasts) detected in the bone marrow over 20% at the time of diagnosis to 5%. Many different ways can be used to achieve this goal.

What is acute myeloid leukemia (AML)?

Acute leukemia is a type of bone marrow cancer that causes a group of cells in the bone marrow that make up the cells we call white blood cells in the blood, to become abnormal in a short time and to proliferate excessively, and with the effect of this proliferation, the blood production in the bone marrow decreases. The word “acute” means that these types of leukemia can progress quickly if left untreated and possibly be fatal within a few months.

There are 2 types:

  1. acute myeloid leukemia (AML)

  2. acute lymphoblastic leukemia (ALL)

AML is also referred to by many other names, such as "acute myelocytic leukemia", "acute myelogenous leukemia", "acute granulocytic leukemia" and "acute non-lymphocytic leukemia". “Myeloid” refers to the type of cell in which this leukemia begins in the bone marrow. Most cases of AML develop from cells that will develop into white blood cells (other than lymphocytes), but some cases of AML can also develop from other blood-forming cells.

What are the causes of acute myeloid leukemia (AML)?

First of all, we should point out that there is no definite known cause of AML. It would be more accurate to gather the causes of acute myeloid leukemia under two main headings. These:

  1. Genetic causes

  2. Effect of environmental factors

When it comes to genetic causes, it is generally not meant to be congenital and known as hereditary causes. Genetic disorders that occur in these diseases are mostly acquired disorders in any period of life. It can be seen in one or more of the genes that make up the chromosomes. Sometimes, genetic disorders can be seen in the form of breaks in the chromosomes and the placement of the broken piece on another chromosome. This can lead to the development of leukemia by causing the cell to become cancerous and have the ability to proliferate excessively.

Among the most common causes of environmental factors, exposure to high doses of radiation (usually it occurs many years after this exposure), smoking or some chemicals that disrupt the structure of cells can be counted. Apart from these, it is known that the incidence of leukemia increases in the course of some blood diseases that we can express as bone marrow laziness. Leukemia may occur in the following years in patients who have received chemotherapy for any type of cancer. Some microbes that we call viruses can trigger the formation of leukemia.

What are the types (classification) of acute myeloid leukemia (AML)?

As our knowledge about AML increases, the classification of the disease also changes. In acute myeloid leukemia (AML), a classification previously called FAB classification based on cell morphologies (structural appearance of the cell) was used more frequently, but after it became clear that genetic and molecular disorders are more important in the onset and clinical course of the disease, the World Health Organization (WHO = WHO) ) made a classification based on genetics.

 

In the FAB classification, there are 8 subtypes (M0, M1, M2, M3, M4, M5, M6, M7) starting from M0 to M7. Except for M3, the treatments are similar.

 

The WHO classification was updated in 2008, 2016 and 2022. In the latest updated version, subtypes are given according to each genetic disorder. In addition, in some genetic anomalies, the blast rate (leukemic cell rate) required for the diagnosis of the disease has been reduced from 20% to 10%.

What are the symptoms of acute myeloid leukemia (AML)?

AML and all acute leukemias are types of leukemia with a very rapid course. While there were no symptoms a week ago or the blood counts were completely normal, both the blood count levels may deteriorate and some symptoms may be observed suddenly within a week. Therefore, attention should be paid to the symptoms mentioned below.

The most common of these symptoms are:

  1. Sudden onset of weakness and fatigue:  It occurs due to the disruption of blood production by leukemia cells invading the bone marrow and the resulting decrease in the number of red blood cells. The decrease in the number of red blood cells of these people also causes a decrease in a protein that carries oxygen to the organs called hemoglobin. Decreased hemoglobin levels can cause fatigue and fatigue, shortness of breath while walking, palpitations and drowsiness.

  2. Bleeding:  Leukemia cells that invade the bone marrow may cause a tendency to bleed by causing a decrease in the production of cells called "platelets", known as coagulation cells. Therefore, these patients may have bleeding gums, bruising on the body, and nosebleeds.

  3. Infection/Inflammation:  Again, leukemia cells that invade the bone marrow disrupt the production of cells called "leukocytes", known as warrior cells, and reduce their number. These cells are the body's defense cells. Defects in their production can lead to the development of infection. Depending on the location of the current infection, symptoms such as fever, sore throat, cough, runny nose, post-nasal drip, inflammation of the skin, ie soft tissue, can be observed.

Acute leukemias start in the bone marrow, but in most cases quickly pass into the blood. Sometimes it can spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles. In this case, some symptoms may occur depending on the organ where the disease has spread. It should be noted that the presence of one or more of the following symptoms does not make a diagnosis of acute leukemia. It should be checked whether these symptoms are accompanied by abnormalities in the blood count. We can list the mentioned symptoms as follows:

  • Cough, hiccups:  It may occur due to the spread of the disease to the lungs or enlargement of the lymph nodes in the chest cavity.

  • Shortness of breath:  It may also occur due to the spread of the disease to the lungs or the enlargement of the lymph nodes in the chest cavity, as well as the decrease in blood values ​​or lung infection.

  • Enlargement in the liver, spleen or lymph nodes:  It can be seen due to the invasion of leukemia cells from the bone marrow and invading these organs via blood or lymph.

  • Headache, dizziness, balance disorder, low back pain, drowsiness:  It can be seen due to the spread of leukemia cells to the nervous system, especially the brain, or to the spinal cord.

  • Bone pains:  Leukemia cells that invade the bone marrow can cause all kinds of bone pain.

  • Abdominal pain, constipation, nausea, vomiting:  Acute leukemias may rarely spread to the gastrointestinal system, which is expressed as the "gastro intestinal system", and may cause the symptoms mentioned.

How is acute myeloid leukemia (AML) diagnosed?

Your doctor can diagnose acute leukemia based on a physical exam, medical questions, and tests that look at the person's blood and bone marrow cells.

Medical History

  • Your medical history is questioned by your doctor and information about your health habits, past illnesses and treatments is collected.

Physical Examination

  • Your general body examination is done by your doctor. This exam checks your physical health for unusual signs or symptoms. During the physical examination, your lymph nodes, spleen and liver will be examined for enlargement.

Complete Blood Count (CBC)

  • A blood sample is collected and examined to measure various parameters:

• The amount of red blood cells (red blood cells), white blood cells (white blood cells), and platelets (clotting cells)

• The amount of hemoglobin bound to red blood cells

• The ratio of the sample consisting of red blood cells, called hematocrit, is determined by this examination.

Blood and Urine Biochemistry Tests

  • It is a blood sample analysis to measure the levels of certain substances that organs and tissues release into the bloodstream. Unusually high or low levels of these substances may be helpful in diagnosing the disease.

Peripheral Blood Smear

  • Your doctor will examine your blood sample under a microscope for changes in the shape of the blood cells. It is very important in the diagnosis of acute myeloid leukemia. Your doctor can also determine the amount, type, and platelet count of white blood cells this way.

Bone Marrow Aspiration and Biopsy Procedure

  • Bone marrow aspiration and biopsy is a procedure to collect and examine bone marrow, a spongy tissue found in some of your large bones. It is used to diagnose and follow up acute leukemia. Bone marrow biopsy and bone marrow aspiration are often done at the same time.

  • Bone marrow aspiration and biopsy are usually taken from the apex of the posterior part of the pelvis. By entering this area with the needle to be used in the procedure, the skin and subcutaneous tissues are passed, first the bone is reached, and the needle is inserted into the bone marrow region by advancing. The hematologist or oncologist who performed your biopsy adds a syringe (syringe) to the needle and takes a sample from the liquid portion of the bone marrow. Aspiration takes only a few minutes. If it is understood that there is no marrow tissue, the process can be repeated. Sometimes the bone marrow fluid may not be drawn into the injector at all due to the condition of your disease. In this case, only a biopsy is taken. In a bone marrow biopsy, a sample of bone marrow tissue is taken by entering the bone. For bone marrow biopsy, a larger needle is used and a piece of at least 1.5 cm (1.5-3.5 cm) is taken from the solid bone marrow tissue to be sufficient for the sample with this needle. Like aspiration, a biopsy takes only a few minutes. Both samples are then examined under a microscope by the hematologist and pathologist to look for bone marrow cancer cells and monitor for healthy blood cells. A diagnosis of acute leukemia can be made with the presence of leukemia cells above a certain rate in the bone marrow.

Genetic analysis

  • After your bone marrow sample is taken, the tissue cells are analyzed under a microscope to look for the genetic abnormalities we mentioned at the beginning of the article.

Immunohistochemistry

  • It is the analysis of antigens on the surface of bone marrow cells, which we can call a kind of identity marker.

Flow cytometry

  • The flow cytometry test reveals other characteristics of cells, such as the size, shape, and presence of tumor markers on the cell surface. For this test, cells are marked with a fluorescent dye and placed in a liquid. The properties of the cells can be determined by passing a light beam through the cells and looking at the scattering of the light. It is an indispensable analysis in the diagnosis of acute leukemia.

How is acute myeloid leukemia (AML) treated?

The treatment of acute leukemia requires patience both for the patient, their relatives and the healthcare team that treats them. The treatment takes a long time.

 

The primary goal in treatment is to reduce the rate of leukemia cells (blasts) detected in the bone marrow over 20% at the time of diagnosis to 5%. 

 

To achieve this goal, the following path is followed:

  1. Standard Remission Induction therapy:  It is the treatment to put the disease into remission, that is, to reduce the leukemia cells below the target rate. It is the standard treatment for patients under 60 years of age and with good clinical performance. Treatment may include both chemotherapy and smart drugs that target existing surface antigens or genetic disorders. The duration of chemotherapy is 7 days. 8-21 if a mutation called smart drug FLT-3 is detected. available between days. It takes approximately 1 month for the leukemia cells in the bone marrow to be destroyed and replaced by normal cells, if no additional complications occur. During this period, the patient should be followed up in an inpatient setting.

  2. Consolidation therapy:  If the rate of leukemia cells has fallen below 5%, that is, remission has been achieved, this is the treatment to maintain remission. It can also be called reinforcement therapy.

  3. Maintenance treatment: In patients who have undergone transplantation and have FLT-3 mutation, maintenance treatment with smart drugs can be performed. There is no clear consensus on how long this treatment will last.

FREQUENTLY ASKED QUESTÄ°ONS ABOUT ACUTE MYELOÄ°D LEUKEMÄ°A (AML)

How is the risk group determined in AML?

In AML, the risk group is determined according to the genetic and molecular disorders revealed by the examination of samples taken from the bone marrow or blood.

 

Basically, there are 3 risk groups:

  • good risk group

  • medium risk group

  • bad risk group.

What is the life expectancy of acute myeloid leukemia?

In acute myeloid leukemia, life expectancy is associated with treatment success. It is not correct to give a clear life expectancy, as the success of treatment varies according to the clinical characteristics of both the patient and the disease. For this reason, it would be a more rational approach to completely get rid of the disease, that is, to give healing rates. While the chance of cure in AML was around 10-50% in the 1970s, it has approached around 70% after the 2010s with the introduction of stem cell transplantation and smart drugs. This increase is more pronounced especially in patients under 60 years of age.

Is there any chance of recovery from acute myeloid leukemia (AML)?

AML is a type of hematological cancer that has a chance to be completely cured. There is almost no risk of recurrence after 5 years in patients whose treatment is completed.

What is acute myeloid leukemia (AML) m3?

AML-M3 is a subtype of AML given according to the FAB classification. It is also called acute promyelocytic leukemia. It arises with the change between the two chromosomes of the genetic region broken from the 15th and 17th chromosomes. This change stops white blood cell maturation in the bone marrow, causing accumulation and excessive proliferation of promyelocytes, a group of cells in the developmental stages. Treatment differs from other types of AML.

What is acute myeloid leukemia (AML) Staging?

There is no staging in all acute leukemias, including AML. The disease starts quickly and spreads quickly. For this reason, no staging is performed as in other hematological cancers or oncological cancers.

Can bone marrow transplant be performed in acute myeloid leukemia (AML)?

Not every AML patient is transplanted. Allogeneic stem cell transplantation is recommended for patients under 60 years of age with a risk score of medium or high risk. Considering the clinical performance in patients over 60 years of age, transplantation can be considered according to the risk group.

How should patients be followed up?

It would be more correct to gather the recovery under 2 headings. We can say that the first is remission, that is, taking the disease under control. In this case, if the remission is maintained with consolidation or stem cell transplantation, the patients are followed up for up to 5 years with monthly or, depending on the situation, 3-month follow-ups. At the end of the fifth year, we can talk about the cure of the disease, namely sipa, in which case the follow-ups are made annually. These follow-ups are carried out in order to observe the advanced complications of the treatments rather than the recurrence of the disease.

What is the treatment like in elderly patients diagnosed with acute myeloid leukemia (AML)?

In elderly patients diagnosed with AML, standard remission induction therapy is generally not appropriate because the treatment cannot be tolerated. In these patients, more targeted therapies and smart drugs are used. The most commonly used regimen is the combination therapy of venetoclax and azacitidine.

What should patients pay attention to during the treatment of acute myeloid leukemia (AML)?

Morale comes first at the beginning of the points to be considered in the treatment process of AML. Patients should be aware that they will recover and should always keep their morale high. Since patients are hospitalized during the one-month remission induction treatment period, they should fully comply with the recommendations of the healthcare team and doctors, especially in terms of hygiene. Any additional medication or food supplement should not be used -due to possible drug interactions- without the knowledge of the doctor and healthcare team. In addition, patients receiving chemotherapy develop fatigue and this fatigue does not go away by lying down and sleeping, contrary to expectations. On the contrary, walking and exercising, even if it is short, helps to pass the fatigue.

What are the risks of acute myeloid leukemia (AML)?

The risks of acute myeloid leukemia (AML) can be listed as follows;

  • The person's previous radiotherapy or working in places with high levels of radiation such as nuclear power plants may increase the risk of acute myeloid leukemia (AML).

  • Benzene exposure is also a risk factor for acute myeloid leukemia (AML). It should be noted that cigarettes contain benzene.

  • Congenital DNA disorders, that is, congenital DNA disorders, may pose a risk of developing acute myeloid leukemia (AML).

  • People with pre-existing haematological diseases such as Myelodysplastic Syndrome, Essential thrombocytosis, Polystemia Vera or Myelofibrosis are at higher risk of developing Acute myeloid leukemia (AML).

  • Acute myeloid leukemia (AML) may occur in patients who have received cancer treatment, especially chemotherapy.

  • There is no genetic transmission in acute myeloid leukemia (AML). However, the risk of developing acute myeloid leukemia (AML) increases in those with a family history of hematological cancer.

  • The risk of acute myeloid leukemia (AML) is slightly higher in men than in women.

  • Acute myeloid leukemia (AML) can be seen in young and old age. However, it can also be seen in childhood. However, acute myeloid leukemia (AML) is more common in advanced ages.

​What should be considered before treatment of acute myeloid leukemia (AML)?

  • In the treatment of acute myeloid leukemia (AML), there is not much that the patient should pay particular attention to. The patient should be more careful about hygiene after starting the treatment.

  • It is not recommended to consume too much raw vegetables and fruits, especially in nutrition, as it is thought to increase the risk of infection in patients. However, raw vegetables and fruits with thick skins, of which hygiene is assured, can be consumed.

  • Chemotherapy is often used to treat acute myeloid leukemia (AML). If some genetic mutations are detected, smart drugs can be added to the treatment. The possibility of interaction of previously used drugs with drugs used during treatment should be evaluated. For this reason, it is important for patients to tell their doctor about any medications or supplements they have used before.

  • If the patient is using it, it is important to stay away from smoking and alcohol.

However, during the treatment of acute myeloid leukemia (AML), there are issues that the treating doctor should pay attention to.

The patient's liver and kidney functions should be checked.

It is important to review chronic diseases. .

Previous medications used by the patient should be checked.

It may be vital to control conditions such as severely uncontrolled hypertension or lung disease before treatment.

Who can be recipient for a bone marrow transplant and how is it done?

  • The question of who and how bone marrow transplantation is performed in acute myeloid leukemia (AML) disease may vary according to the risk group of the patient.

  • Patients are divided into risk groups according to their current genetic mutations and chromosome breaks. Stem cell transplantation is not performed for low risk groups. These patients are mostly treated with chemotherapy and consolidation treatment, that is, consolidation treatments. Stem cell transplantation may not be preferred because of the complications that may occur in patients whose course of the disease can go well.

  • Patients in the middle and high risk groups are first taken to stem cell transplantation after they are brought to normal, that is, after remission is achieved.

Is acute myeloid leukemia (AML) dangerous?

Acute myeloid leukemia (AML) is a rapidly growing cancer. While no abnormality is observed in the person in the controls made recently, millions of leukemia cells can multiply in the body for a short time. Acute myeloid leukemia (AML), which also collapses the immune system because of its rapid course, is a disease that can be fatal if treatment is not started immediately.

What does AML FLT3 positive mean?

FLT3 is an acquired genetic mutation in acute myeloid leukemia (AML). FLT3 is a genetic mutation that is also responsible for the formation mechanism of the disease. If the disease cannot be controlled, it may develop later. FLT 3 positivity has two significance in AML.

The presence of AML FLT3 puts the patient in the high-risk group. In this case, patients need a stem cell transplant.

There are smart drugs that can correct the AML FLT3 mutation. In addition to normal chemotherapy, smart drugs are given that can correct the AML FLT3 mutation, both in first-line therapy and in subsequent reinforcement treatments.

What is the difference between ALL and AML?

​ALL is the abbreviation for Acute Lymphoblastic Leukemia. Acute Lymphoblastic Leukemia (ALL) and Acute myeloid leukemia (AML) are both acute leukemia. Both diseases are cancers that originate from primitive cells where the white blood cells in the blood are produced in the bone marrow. ALL originates from lymphoid cells, whereas AML originates from myeloid cells. The difference in their names is due to the cells from which they originate. Considering their treatment and follow-up, both are different from each other.

What does acute mean in cancer?

In cancer, acute means rapid course, that is, sudden onset. Acute in the definition of acute leukemia means the sudden onset of the disease in a person who had everything normal recently. Catching acute leukemia in routine blood checks depends on luck. There can be very different results between two routine blood counts.

Is acute leukemia contagious?

Acute leukemia is not a microbial disease. It is not contagious. There is no hereditary hereditary transmission. The disease is not transmitted by contact with the sick person or by breathing.

In which blood is cancer detected?

Cancers can be divided into two main groups. Oncological, that is, cancers arising from organs and hematological cancers arising from cells in the bone marrow and blood.

In cancers that develop in oncological organs, cancer may be suspected by blood count or other tests. However, the main thing in organ cancers is the detection of a mass or a lesion in any part of the body.

Acute myeloid leukemia (AML) may raise suspicion with the data revealed in the complete blood count test. Low white blood cell (WBC) or high white blood cell (WBC) and accompanying low hemoglobin and thrombocyte levels can create suspicion for AML.

AML is one of the first diseases that come to mind if the patient has weakness, fatigue, bleeding gums, bruising, fever, bone pain, together with the data in the blood values.

What is the first sign of blood cancer?

​The first symptom of blood cancer is fatigue. But fatigue may not always be the first sign of blood cancer. Bruising, bleeding gums, fever, bone pain may also be the first symptoms.

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