Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It is a rare disease, accounting for around 0.8% of all diagnosed cancers. This type of cancer affects a group of white blood cells called myeloid cells, which normally develop into various types of mature blood cells, such as red blood cells, white blood cells and platelets.
Acute myeloid leukemia occurs when a mutation changes bone marrow cells and causes them to continue growing and dividing unchecked. Normally, they grow at a set rate and die at a specified time. As the blood cell production becomes excessive, the bone marrow also starts producing immature cells that develop into leukemic white blood cells called myeloblasts. These abnormal cells are unable to function properly and can build up and crowd out healthy cells.
The accumulation of these dysfunctional blast cells in the bone marrow leads to a decrease in the production of normal blood cells, including red blood cells (causing anemia), platelets (causing bleeding problems), and functional white blood cells (weakening the immune system).
The progression of acute myeloid leukemia (AML) can vary widely from person to person. AML is considered an aggressive type of leukemia, and its progression is generally rapid compared to other forms of leukemia. The disease can evolve over a matter of weeks to a few months. However, the specific speed of progression can depend on several factors, including the subtype of AML, genetic and molecular factors, the patient’s overall health, the response to treatment, and the patient’s age.
If acute myeloid leukemia (AML) is left untreated, it can have serious and potentially life-threatening consequences. The disease is aggressive and progresses rapidly, leading to a number of complications that can significantly impact a person’s health. Some of the potential outcomes of untreated AML include low blood cell count, infections, bleeding disorders, organ dysfunction and hemorrhage.
AML Causes and Risk Factors
The exact cause of these genetic mutations that trigger AML is not always clear, but they can result from a combination of reasons. The only proven risk factors for AML are:
- Age: The risk of developing AML becomes greater as people get older.
- Gender: AML is more common in males than in females.
- Family History: Having a close relative with AML increases a person’s risk of getting the disease.
- Smoking: People who smoke are at a greater risk of developing AML.
- Exposure to Chemicals: Long-term exposure to benzene (a solvent used in the rubber industry, oil refineries, chemical plants, shoe manufacturing, and gasoline-related industries) increases a person’s risk of developing AML. It is also believed that exposure to formaldehyde increases the risk of developing AML.
- Exposure to Radiation: People who have been exposed to high-dose radiation have a greatly increased risk of developing AML.
- Blood Disorders: The risk of AML is higher among those with blood disorders, such as polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis. The risk increases if the person has been treated for these conditions with chemotherapy or radiation.
- Genetic Syndromes: Certain genetic syndromes and disorders have been associated with an increased risk of developing AML:
- Aplastic Anemia
- Ataxia Telangiectasia
- Bloom Syndrome
- Diamond-Blackfan Anemia (DBA)
- Down Syndrome (Trisomy 21)
- Familial Platelet Disorder Syndrome
- Fanconi Anemia
- Klinefelter Syndrome
- Kostmann Syndrome
- Li-Fraumeni Syndrome
- Myelodysplastic Syndrome (MDS)
- Neurofibromatosis Type-1
- Polycythemia Vera
- Shwachman-Diamond Syndrome
- Trisomy 8
- Wiskott-Aldrich Syndrome
The development of AML is complex and involves multiple genetic alterations that drive the disease’s progression, making it a challenging condition to treat.
Most symptoms of AML are caused by a reduction in the number of healthy blood cells in the body due to the crowding of leukemia cells.
A drop in red blood cell count (anemia) may cause the following signs and symptoms:
- Feeling cold
- Shortness of breath
- Dizziness or lightheadedness
- Pale skin
A drop in platelet count may cause easy bruising and bleeding, while a decrease in white blood cells can lead to frequent infections.
Early signs of AML often mimic symptoms of the flu, such as fever, fatigue, loss of appetite, bone pain, and shortness of breath.
AML may be present if certain symptoms and signs are present, but a diagnosis and subtype must be determined through specialized testing. The Hemato-Oncology Division at Sheba Medical Center carefully evaluates each patient’s case to decide which test procedures to run.
AML typically progresses quickly, so early diagnosis is essential. It is crucial to select a highly qualified medical team to manage your diagnosis because AML is also a relatively uncommon disease. Our Sheba pathologists and clinicians have extensive experience and cutting-edge tools to diagnose leukemia quickly and accurately. They have received their training at some of the best cancer centers in the world.
- Blood Tests: Blood tests are usually the first step in diagnosing leukemia. These include taking a CBC (complete blood count) and a blood smear. A CBC is a blood test that analyzes the count of red blood cells, white blood cells, and platelets in the blood, while a peripheral blood smear is a laboratory test that involves examining the blood under a microscope for changes in the number and appearance of cells. The changes in the amount and appearance of different blood cells can help diagnose leukemia.
- Bone Marrow Samples: Leukemia begins in the bone marrow, so checking bone marrow samples is a significant part of testing for cancer. Typically, both a bone marrow biopsy and a bone marrow aspiration are performed. Cytogenetic analysis is used to examine the cells in a blood or bone marrow sample, inspecting for particular changes in the chromosomes. The results of these diagnostic procedures are highly accurate for detecting AML.
- Chromosome Tests: Leukemia cells sometimes exhibit chromosomal changes that can help specialists identify the type of AML and the best course of treatment moving forward.
- Spinal Tap or Lumbar Puncture: A spinal tap or lumbar puncture may be performed to determine whether or not leukemia has spread to the central nervous system.
- Imaging Scans: May be performed to assess whether AML has spread to the area surrounding the brain and spinal cord.
- Cytochemistry: In this laboratory test, cells are exposed to a dye that only reacts with leukemia cells. The color changes in the cells indicate whether they are cancerous and if so, which type of leukemia it is.
- Flow Cytometry and Immunohistochemistry: This laboratory test uses a sample of cells that are treated with antibodies that only attach to certain proteins on the cells. This helps to determine exactly which type of leukemia a person has.
Factors that affect prognosis and treatment
The prognosis for acute myeloid leukemia (AML) can vary widely depending on several factors, including the patient’s age, overall health, specific genetic and molecular characteristics of the leukemia cells, and how well they respond to treatment. AML is a complex disease, and its prognosis can be challenging to predict accurately.
Here are some key factors that can influence the prognosis of AML:
- Age: Younger patients tend to have a better prognosis than older patients. AML is more aggressive in older individuals and can be associated with additional health issues that affect treatment options and outcomes.
- Cytogenetics and Molecular Abnormalities: The genetic and molecular characteristics of the leukemia cells play a significant role in determining prognosis. Certain genetic mutations, such as those involving genes like FLT3, NPM1, and CEBPA, can impact the response to treatment and overall outcomes.
- Response to Initial Treatment: A patient’s response to the initial induction chemotherapy is a strong indicator of prognosis. Achieving a complete remission (no evidence of leukemia cells in the bone marrow) after the initial treatment is associated with a better prognosis.
- Relapse: If AML returns after treatment (relapse), the prognosis becomes less favorable. The time between achieving remission and the occurrence of relapse can also impact prognosis.
- Cell Transplantation: For some patients, undergoing a cell transplant (bone marrow or cell transplant from a donor) can improve the chances of long-term remission and survival. The decision to undergo transplantation is influenced by various factors, including age, overall health, and availability of a suitable donor.
- Overall Health: Patients with underlying health conditions may have a more challenging time tolerating intensive treatments and may experience more complications.
- Secondary AML: AML that develops as a result of previous cancer treatments or other factors can have a different prognosis.
- New Treatment Approaches: Advances in AML treatment, including targeted therapies and immunotherapies, are continually evolving. These newer treatments can impact prognosis, especially for patients with specific genetic mutations or molecular profiles.
It’s important to note that AML treatment is complex and often involves multiple rounds of chemotherapy, potentially followed by stem cell transplantation. Prognosis is typically discussed on a case-by-case basis between the patient and their medical team, taking into consideration all relevant factors.
The progression of AML can be categorized into different stages, each with its own characteristics and implications for treatment and prognosis.
The three main stages of AML are:
Untreated (Newly-Diagnosed) AML
When an individual is first diagnosed with AML, they are in the untreated or newly-diagnosed stage. This stage is characterized by the presence of a high number of immature, abnormal white blood cells called blast cells in the bone marrow and peripheral blood. These blast cells crowd out healthy blood cells, leading to symptoms such as fatigue, anemia, increased susceptibility to infections and bleeding diathesis.
The goal of treatment during this stage is to induce remission, which means reducing the number of blast cells in the bone marrow and blood to a level where normal blood cell production can resume.
AML in Remission
After successful treatment, when the number of blast cells in the bone marrow and blood drops to a normal or near-normal level, the patient is considered to be in remission. Complete remission (CR) is achieved when fewer than 5% of the cells in the bone marrow are blast cells, and blood counts return to normal levels.
During this phase, the patient’s symptoms generally improve, and they might not require intensive treatment like they did during the initial diagnosis. However, it’s important to note that even though the symptoms might improve, the risk of recurrence remains. Patients in remission often undergo follow-up tests, including bone marrow biopsies and blood tests, to monitor for any signs of relapse.
Recurrent AML, also known as relapsed AML, occurs when the leukemia reappears after a period of remission. This can happen due to a small number of residual leukemia cells that were not completely eliminated during the initial treatment, or because of the development of new genetic mutations that make the leukemia cells resistant to the previously used treatment.
Recurrent AML presents a new challenge, as it can be more difficult to treat than the initial diagnosis. The treatment approach for recurrent AML might involve different chemotherapy regimens, targeted therapies, experimental treatments, and possibly stem cell transplantation if the patient is eligible.
It’s important to recognize that the prognosis for AML varies depending on the specific characteristics of the leukemia cells, the patient’s age and overall health, and how well they respond to treatment.
At Sheba Medical Center, world-renowned multidisciplinary specialists will collaborate to ensure that you benefit from the most progressive and personalized treatments for acute myeloid leukemia. Treatment options will vary based on the type of AML, your age, and your general state of health, among other factors. Medical oncologists, hematologists, and radiation oncologists will combine their experience and knowledge to design your integrative therapies.
Treatment options at Sheba include:
Chemotherapy is the primary treatment for most adults with AML, and it is generally divided into phases. The first phase is induction, and it is short and intensive – with the goal of killing as many leukemia cells as possible to lead to remission. The second phase is consolidation (post-remission), and it works to destroy the remaining inactive cancer cells. The third phase is maintenance. Only certain types of AML require the maintenance phase, in which the patient is treated with chemotherapy for months or years following consolidation.
Bone Marrow Transplant
A bone marrow transplant can be used as part of initial treatment for AML or part of treatment for disease relapse. This procedure involves depleting diseased bone marrow with chemotherapy or radiation and then intravenously infusing healthy cells into the patient, which then multiply and develop into healthy bone marrow.
Located within Sheba Medical Center, the largest hospital in Israel, the Department of Bone Marrow Transplantation boasts an array of 14 exclusive chambers. These are complemented by advanced and extensive laboratories and clinics, enabling the seamless execution of every phase of the transplant process on the premises.
Having successfully conducted over 2,000 transplants up to this point, the department boasts a multifaceted staff of globally acclaimed experts. This team encompasses hematologists, medical oncologists, and radiation oncologists, collaborating harmoniously to furnish top-tier, cutting-edge therapies tailored to the distinctive needs of each patient.
Find out more on why many choose Sheba for a bone marrow transplant for acute myeloid leukemia.
Radiation therapy applies high-energy x-rays to kill cancer cells. This treatment is not typically part of the primary treatment for AML, but it may be helpful for treating leukemia that has spread, to shrink a tumor, or before a bone marrow transplant.
Throughout the entire course of your treatment at Sheba Medical Center, we will stay focused on your overall quality of life. We aim to make your therapy as efficient and comfortable as possible. To that end, we offer a full range of support services – including social workers, alternative therapies, and nutritional counseling – to ensure that all of your individual needs are met as you cope with cancer.
Targeted therapy drugs work differently from chemotherapy drugs because they are made to identify, target and attack specific cancer cells without harming normal cells. In some Acute Myeloid Leukemia cases, they have been shown to be more effective than chemotherapy drugs and they often have different side effects. Examples of oral targeted agents that may be prescribed for AML include midostaurin, gilteritinib, IDH inhibitors (ivosidenib, enasidenib), and glasdegib.
CAR T-cell Therapy
CAR T-cell therapy is an innovative procedure that makes use of your own immune system to seek and destroy cancerous cells. After some blood is taken from the patient, the T-cells, a type of immune cell, are separated from the rest of the blood in a special laboratory. The T-cells are then genetically engineered to produce chimeric antigen receptors (CARs). The engineered T-cells are then given some time to multiply in the laboratory and are later injected back into the patient. The CARs allow the T-cells to recognize, target and destroy cancer cells.
Sheba is the only medical center worldwide that offers this advanced treatment to AML patients with the t(8;21) translocation as part of a clinical trial. At Sheba, CAR T-cells are engineered in-house in a specialized laboratory, and as a result the entire process, from lymphocyte collection to patient delivery, only takes about 13 days.
Holistic Approach at Sheba Medical Center
Finding the best medical staff and facilities for your treatment is crucial after receiving a leukemia diagnosis because it can be devastating. The Hemato-Oncology Division at Sheba Medical Center in Israel provides you with the most cutting-edge, customized therapies for leukemia developed by medical professionals who are world leaders in this field. Acute myeloid leukemia (AML) cases will be assessed by a multidisciplinary team of medical experts, including hematologists, radiation oncologists, and general oncologists, to determine the most effective course of treatment.
The Hemato-Oncology Division at Sheba uses cutting-edge technology and the most recent findings from clinically based research to create individualized treatment plans for each patient. We use a precise HLA laboratory and our molecular laboratory to pinpoint the best donor match in the event that a bone marrow transplant is required. Sheba is a participant in the National Marrow Donor Program as well, in case a genetically compatible donor cannot be found.
Our approach to treating cancer is holistic, considering the whole body and not just AML. Beginning with your initial consultation all the way through follow-up appointments and testing, our compassionate team of medical professionals will strive to preserve your quality of life and keep you as comfortable as possible. Cancer can have far-reaching effects on your physical and emotional well-being, which is why your treatment program at Sheba includes a variety of support services.
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Sheba Medical Center provides innovative, personalized medical care to patients from around the world. We are the largest, most comprehensive hospital in the Middle East and dedicated to providing advanced and compassionate medicine for everyone. We welcome all cases, including the rarest and the most challenging. Our medical teams collaborate to provide the best possible health outcomes. From your initial inquiry through the long-term follow-up care, we are here for you.
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