What are the other Names for this Condition? (Also known as/Synonyms)

• Acute Granulocytic Leukemia
• Acute Myelogenous Leukemia
• Acute Non-Lymphocytic Leukemia

What is Acute Myeloid Leukemia? (Definition/Background Information)

• Acute Myeloid Leukemia (AML) is a type of cancer that starts in the bone marrow, where blood cells are produced. It is characterized by the rapid growth of abnormal myeloid cells, which are a type of white blood cell responsible for fighting infections
• Acute Myeloid Leukemia typically progresses rapidly, leading to an overproduction of immature white blood cells called blasts. These blasts crowd out normal blood cells, leading to symptoms such as anemia, infections, and bleeding problems
• Acute Myeloid Leukemia originates in the myeloid cells responsible for producing red blood cells, platelets, and certain types of white blood cells. In AML, these myeloid cells become cancerous and fail to mature properly, leading to an accumulation of immature cells in the bone marrow and bloodstream
• Acute Myeloid Leukemia can be associated with certain genetic mutations affecting how blood cells develop and function. These mutations can impact the prognosis and treatment options for individuals with AML. Hence, individuals with certain genetic mutations or pre-existing blood disorders may be at increased risk of developing AML
• The risk factors for Acute Myeloid Leukemia include exposure to certain chemicals such as benzene, previous chemotherapy or radiation therapy for other cancers, genetic syndromes like Down syndrome, and older age (AML is more common in adults than in children)
• The common signs and symptoms noted with Acute Myeloid Leukemia include fatigue, shortness of breath, pale skin, easy bruising or bleeding, frequent infections, fever, and swollen lymph nodes
• A diagnosis of Acute Myeloid Leukemia involves blood tests, bone marrow biopsy, and genetic testing to confirm the presence of abnormal cells and identify specific genetic mutations that may guide treatment decisions
• The treatment measures for Acute Myeloid Leukemia typically involve chemotherapy to destroy cancer cells and allow normal blood cell production to resume. Stem cell transplantation may also be considered for certain individuals, especially those with high-risk or relapsed AML
• The prognosis varies depending on factors such as the individual's age, overall health, specific genetic mutations, and response to treatment. Advances in treatment options have improved outcomes for many individuals with Acute Myeloid Leukemia, but it remains a challenging disease to treat, especially in older adults

According to the WHO Classification of Hematolymphoid Tumors (2022), 5th Ed., Acute Myeloid Leukemia is classified in the following manner:

• Acute Myeloid Leukemia with defining genetic abnormalities        
  • Acute promyelocytic leukemia with PML::RARA fusion
  • Acute Myeloid Leukemia with RUNX1::RUNX1T1 fusion
  • Acute Myeloid Leukemia with CBFB::MYH11 fusion
  • Acute Myeloid Leukemia with DEK::NUP214 fusion
  • Acute Myeloid Leukemia with RBM15::MRTFA fusion
  • Acute Myeloid Leukemia with BCR::ABL1 fusion
  • Acute Myeloid Leukemia with KMT2A rearrangement
  • Acute Myeloid Leukemia with MECOM rearrangement
  • Acute Myeloid Leukemia with NUP98 rearrangement
  • Acute Myeloid Leukemia with NPM1 mutation
  • Acute Myeloid Leukemia with CEBPA mutation
  • Acute Myeloid Leukemia, myelodysplasia-related
  • Acute Myeloid Leukemia with other defined genetic alterations
• Acute Myeloid Leukemia, defined by differentiation          
  • Acute Myeloid Leukemia with minimal differentiation
  • Acute Myeloid Leukemia without maturation
  • Acute Myeloid Leukemia with maturation
  • Acute basophilic leukemia
  • Acute myelomonocytic leukemia
  • Acute monocytic leukemia
  • Acute erythroid leukemia
  • Acute megakaryoblastic leukemia

Who gets Acute Myeloid Leukemia? (Age and Sex Distribution)

Acute Myeloid Leukemia (AML) can affect individuals of various ages and sexes.

• It is more common in adults than in children. A majority of AML cases occur in adults, particularly those over the age of 60
• The median age at diagnosis is around 68 years, with a higher incidence observed in older adults
• While AML is relatively rare in children, it can still occur, especially in infants and adolescents. The incidence in children peaks during the first few years of life and then again during adolescence
• AML affects both males and females, with no significant predilection for either sex. However, certain subtypes of AML may show slight variations in incidence between males and females

Overall Incidence:

• Acute Myeloid Leukemia accounts for approximately 1% of all cancers and is considered one of the more common types of leukemia in adults
• The incidence of AML has been relatively stable over the years, with slight variations in specific age groups and populations

Worldwide, Acute Myeloid Leukemia can occur in individuals of any racial or ethnic background.

What are the Risk Factors for Acute Myeloid Leukemia? (Predisposing Factors)

Acute Myeloid Leukemia (AML) has several risk factors that can predispose individuals to develop this type of leukemia. The key risk factors include:

Family history:

• Having a family history of leukemia or other blood disorders may increase the risk of developing AML
• Inherited genetic mutations related to blood cell production and function can contribute to the familial clustering of leukemia cases

Immune system suppression:

• Conditions or treatments that suppress the immune system, such as organ transplantation and certain autoimmune diseases, can elevate the risk
• Immunosuppression can disrupt normal immune surveillance mechanisms, allowing abnormal cells to proliferate unchecked

Exposure to certain chemicals:

• Prolonged exposure to benzene, a chemical found in some workplaces such as factories, refineries, and chemical plants, is a known risk factor for AML
• Other chemicals like formaldehyde and certain pesticides have also been linked to an increased risk

Previous chemotherapy or radiation therapy:

• Individuals who have undergone previous chemotherapy or radiation therapy for other cancers may have an increased risk of developing AML as a secondary malignancy
• Certain chemotherapy drugs, such as alkylating agents and topoisomerase II inhibitors, are known to increase the risk

Genetic syndromes:

• Genetic syndromes such as Down syndrome, Bloom syndrome, Fanconi anemia, and Li-Fraumeni syndrome are associated with an elevated risk of developing AML
• These syndromes often involve genetic mutations that affect the functioning of blood cells and increase the likelihood of leukemia

Age:

• AML is more common in older adults, particularly those over the age of 60
• Age-related changes in the bone marrow and cumulative exposure to environmental factors over time may contribute to the increased risk in older individuals

Smoking:

• Cigarette smoking has been linked to an increased risk, especially in individuals with long-term smoking habits
• The chemicals in tobacco smoke, including benzene and other carcinogens, can contribute to the development of leukemia

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Acute Myeloid Leukemia? (Etiology)

Acute Myeloid Leukemia (AML) can be caused by various factors, including genetic mutations and environmental exposures.

Genetic mutations:

• Mutations in specific genes involved in cell growth, differentiation, and apoptosis (programmed cell death) can lead to the development of AML
• Common genetic mutations associated with AML include mutations in the FLT3, NPM1, and CEBPA genes, among others
• These mutations can disrupt normal cell functions and promote the uncontrolled growth of immature myeloid cells

Chromosomal abnormalities:

• Chromosomal abnormalities, such as translocations, deletions, and duplications of genetic material, are frequently found in AML cells
• These chromosomal changes can alter the expression of critical genes involved in hematopoiesis (blood cell formation) and contribute to leukemic transformation

Environmental exposures:

• Prolonged exposure to certain chemicals, such as benzene, formaldehyde, and certain pesticides, has been linked to an increased risk of developing AML
• Occupational exposure to these chemicals in industries like manufacturing, agriculture, and petroleum refining can pose a risk to workers

Previous cancer treatments:

• Some chemotherapy drugs used to treat other cancers, particularly alkylating agents and topoisomerase II inhibitors, can cause damage to DNA and increase the risk of secondary AML
• Radiation therapy, especially when administered to the bone marrow or surrounding tissues, can also predispose individuals to AML

Genetic syndromes:

• Certain genetic syndromes, such as Down syndrome, Bloom syndrome, and Fanconi anemia, are associated with an increased risk of AML
• These syndromes involve inherited mutations that affect DNA repair mechanisms and cell proliferation, contributing to leukemia development

Age and immune system changes:

• Aging is a risk factor for AML, as age-related changes in the bone marrow microenvironment and immune system can create conditions favorable for leukemic transformation
• Immunosuppression, whether due to medical conditions, treatments like organ transplantation, or medications that suppress the immune system, can also play a role in AML development

Family history:

• While most cases of AML are not inherited, a positive family history of leukemia or other blood disorders may indicate a genetic predisposition to the disease
• Inherited genetic mutations related to blood cell development and function can contribute to familial clustering of AML cases

What are the Signs and Symptoms of Acute Myeloid Leukemia?

Acute Myeloid Leukemia (AML) presents with a range of signs and symptoms. this may vary from one individual to another and can be mild or severe in presentation. These may also vary depending on the subtype of AML.

General symptoms:

• Fatigue and weakness are common early signs of AML due to decreased red blood cell production (anemia)
• Unexplained weight loss and loss of appetite may occur as the disease progresses

Hematologic symptoms:

• Low platelet counts can result in easy bruising or bleeding, such as frequent nosebleeds, bleeding gums, or petechiae (small red spots on the skin)
• Excessive bleeding may occur after minor injuries or surgeries

Infections:

• AML can weaken the immune system, leading to frequent infections like pneumonia, urinary tract infections, and skin infections
• Fever and chills may accompany these infections, which may be difficult to resolve

Bone and joint pain:

• Bone pain, especially in the long bones of the arms and legs, can occur as leukemia cells infiltrate the bone marrow
• Joint pain and swelling, resembling arthritis symptoms, may also be present

Enlarged organs:

• Enlarged lymph nodes, particularly in the neck, armpits, and groin, may be noticeable due to increased white blood cell production
• The liver and spleen may also enlarge, causing abdominal discomfort or fullness

Skin changes:

• Pallor (pale skin) is common due to anemia, and individuals with AML may appear unusually pale
• Easy bruising and tiny red spots on the skin (petechiae) may be visible

Respiratory symptoms:

• Shortness of breath, especially with exertion, can occur due to anemia and reduced oxygen-carrying capacity of the blood
• A persistent cough or difficulty breathing may indicate lung complications or infections

Neurological symptoms:

• Headaches, dizziness, and confusion may occur in some cases, particularly if leukemia cells have spread to the central nervous system
• Neurological symptoms are less common but should be evaluated promptly if present

Other symptoms:

• Swollen gums and frequent infections in the mouth or throat may occur, affecting dental health
• Unexplained fevers, night sweats, and overall malaise (feeling unwell) are nonspecific but may accompany AML

How is Acute Myeloid Leukemia Diagnosed?

Diagnosing Acute Myeloid Leukemia (AML) involves several steps and tests to confirm the presence of leukemia cells and determine the subtype of AML. These include:

Medical history and physical examination:

• The healthcare provider will review the patient's medical history, including any symptoms and risk factors for leukemia
• A thorough physical examination will be conducted to assess for signs of leukemia, such as enlarged lymph nodes, spleen, or liver

Blood tests:

• A complete blood count (CBC) test is performed to evaluate the levels of red blood cells, white blood cells, and platelets
• Abnormalities in blood cell counts, such as low red blood cell count (anemia), low platelet count (thrombocytopenia), and abnormal white blood cell counts, can indicate the presence of leukemia

Bone marrow aspiration and biopsy:

• Bone marrow aspiration and biopsy are key diagnostic procedures for AML
• A needle is used to remove a small sample of bone marrow from the hip bone (pelvic bone) or sternum (breastbone) for examination under a microscope
• The samples are analyzed to determine the number and appearance of blood cells, detect leukemia cells (blasts), and assess for genetic abnormalities

Cytogenetic testing:

• Cytogenetic testing involves analyzing the chromosomes in leukemia cells to identify specific genetic abnormalities
• This testing helps classify AML into subtypes based on chromosomal changes and can guide treatment decisions

Molecular testing:

• Molecular testing, such as polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH), is used to detect specific genetic mutations associated with AML
• Mutations in genes like FLT3, NPM1, and CEBPA are commonly tested for to determine prognosis and guide targeted therapies

Lumbar puncture (spinal tap):

• In some cases, a lumbar puncture may be performed to collect cerebrospinal fluid (CSF) from around the spinal cord
• This test evaluates whether leukemia cells have spread to the central nervous system, a condition known as central nervous system (CNS) leukemia

Imaging studies: Imaging studies such as X-rays, computed tomography (CT) scans, and magnetic resonance imaging (MRI) may be done to assess for organ enlargement, lymph node involvement, or other complications of AML.

Flow cytometry:

• Flow cytometry is a laboratory technique that analyzes the characteristics of cells, including their surface markers and internal components
• It helps identify abnormal cells, such as leukemia blasts, based on their unique cell surface protein patterns

Pathology and hematology consultation:

• Pathologists and hematologists work together to interpret the results of bone marrow tests, cytogenetic analyses, molecular testing, and other diagnostic studies
• Their expertise is crucial in confirming the diagnosis of AML, determining disease subtypes, and formulating an appropriate treatment plan

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Acute Myeloid Leukemia?

Acute Myeloid Leukemia (AML) can lead to various complications due to the effects of the disease on the blood and bone marrow, as well as its impact on other organs and systems. The potential complications include:

Infections:

• A weakened immune system in AML patients can lead to frequent and severe infections
• Infections may affect the respiratory tract, urinary tract, skin, and other body areas, requiring prompt medical attention and treatment with antibiotics or antifungal medications

Bleeding disorders:

• Low platelet counts (thrombocytopenia) in AML can result in bleeding disorders
• Patients may experience easy bruising, petechiae (small red spots on the skin), nosebleeds, bleeding gums, and prolonged bleeding after minor injuries or procedures

Anemia:

• AML often leads to low red blood cell counts (anemia), which can cause fatigue, weakness, pale skin, shortness of breath, and dizziness
• Severe anemia may necessitate blood transfusions to improve oxygen delivery to tissues and alleviate symptoms

Organ enlargement:

• AML can cause enlargement of organs such as the spleen and liver
• Enlarged organs may lead to abdominal discomfort, fullness, and potential complications such as portal hypertension (high blood pressure in the portal vein) and splenic rupture

CNS involvement:

• In some cases, leukemia cells can spread to the central nervous system (CNS), leading to complications such as headaches, vision changes, seizures, and neurological deficits
• Central nervous system (CNS) leukemia requires specialized treatment and monitoring

Coagulopathies:

• AML patients may develop coagulopathies, including disseminated intravascular coagulation (DIC), a serious condition characterized by widespread blood clotting and bleeding
• DIC can lead to organ damage and requires intensive medical management

Chemotherapy side effects:

• Treatment with chemotherapy, a standard approach for AML, can cause side effects such as nausea, vomiting, hair loss, fatigue, and increased susceptibility to infections
• Chemotherapy-related complications may require supportive care and adjustments to treatment regimens

Secondary cancers:

• Some AML treatments, particularly radiation therapy and certain chemotherapy drugs, can increase the risk of developing secondary cancers later in life
• Regular monitoring and follow-up care are essential to detect and manage any potential secondary malignancies

Endocrine disorders:

• AML can affect hormone production and lead to endocrine disorders, such as thyroid dysfunction and adrenal insufficiency
• Monitoring hormone levels and addressing endocrine abnormalities are important aspects of comprehensive AML care

Psychosocial impact: Acute Myeloid Leukemia and its treatments can have a significant psychosocial impact on patients and their families, including emotional distress, anxiety, depression, and challenges related to coping with the disease and treatment-related changes.

How is Acute Myeloid Leukemia Treated?

Treating Acute Myeloid Leukemia (AML) involves a combination of therapies aimed at eliminating leukemia cells, restoring normal blood cell production, and preventing disease recurrence. The key treatment approaches include:

Chemotherapy:

• Induction therapy: The initial phase of treatment involves intensive chemotherapy to induce remission by destroying leukemia cells in the bone marrow and bloodstream
• Consolidation therapy: After achieving remission, consolidation therapy aims to eliminate any remaining leukemia cells and reduce the risk of relapse
• Chemotherapy regimens: Common chemotherapy drugs used in AML treatment include cytarabine, daunorubicin, idarubicin, and anthracyclines. Combination chemotherapy regimens may be customized based on factors such as age, overall health, and genetic risk

Stem cell transplantation:

• Allogeneic transplant: In some cases, especially for high-risk or relapsed AML, a stem cell transplant (also called bone marrow transplant) may be recommended
• Autologous transplant: Rarely used in AML, an autologous transplant involves using the patient's own stem cells collected before chemotherapy for later transplantation
• Donor selection: Allogeneic transplants require finding a suitable donor (typically a matched sibling or unrelated donor) whose stem cells can replace the diseased bone marrow and produce healthy blood cells

Targeted therapy:

• FLT3 inhibitors: Drugs targeting the FLT3 mutation, such as midostaurin and gilteritinib, are used in AML with FLT3 mutations to inhibit abnormal cell growth
• IDH inhibitors: For AML with IDH1 or IDH2 mutations, medications like ivosidenib and enasidenib target the mutated enzymes to promote normal cell differentiation
• Other targeted therapies: Venetoclax, a BCL-2 inhibitor, may be used in combination with chemotherapy for older adults with AML or those ineligible for intensive chemotherapy

Supportive care:

• Blood transfusions: Red blood cell and platelet transfusions may be needed to manage anemia and bleeding complications
• Antibiotics and antifungals: Prophylactic or therapeutic antibiotics and antifungal medications help prevent and treat infections, a common complication of AML
• Growth factors: Granulocyte colony-stimulating factors (G-CSF) or erythropoiesis-stimulating agents (ESA) may be used to stimulate blood cell production
• Symptom management: Medications and supportive care measures address symptoms such as pain, nausea, and fatigue associated with AML and its treatment

Clinical trials:

• Participation in clinical trials offers access to innovative therapies and investigational drugs that may improve outcomes for AML patients
• Trials may evaluate new chemotherapy regimens, targeted therapies, immunotherapy approaches, and novel treatment combinations

Monitoring and follow-up:

• Regular blood count monitoring, bone marrow assessments, and genetic testing help track treatment response and detect disease recurrence
• Long-term follow-up care focuses on managing treatment-related side effects, monitoring for late effects, and supporting overall well-being

How can Acute Myeloid Leukemia be Prevented?

Preventing Acute Myeloid Leukemia (AML) involves reducing exposure to risk factors and adopting healthy lifestyle practices. The following strategies may be considered:

Avoiding benzene exposure:

• Minimize exposure to benzene, a known risk factor for AML, by following safety guidelines in workplaces where benzene is present (e.g., factories, refineries, chemical plants)
• Use protective equipment such as masks and gloves when working with benzene-containing products

Chemical safety:

• Be cautious with chemicals like formaldehyde and certain pesticides, which are also associated with an increased risk of AML
• Follow safety protocols, use protective gear, and ensure proper ventilation when handling potentially harmful chemicals

Smoking cessation:

• Quit smoking and avoid exposure to secondhand smoke, as cigarette smoke contains carcinogens like benzene that can contribute to AML risk
• Seek support from healthcare professionals or smoking cessation programs to quit smoking successfully

Healthy lifestyle choices:

• Maintain a healthy diet rich in fruits, vegetables, whole grains, and lean proteins. A balanced diet supports overall health and immune function
• Engage in regular physical activity to promote cardiovascular health, strengthen the immune system, and reduce stress

Occupational safety:

• Follow occupational safety guidelines and regulations to minimize exposure to hazardous substances and ensure a safe work environment
• Use protective equipment and adhere to proper handling procedures for chemicals, radiation, and other potential carcinogens

Genetic counseling:

• Consider genetic counseling and testing if there is a family history of inherited genetic syndromes associated with AML, such as Down syndrome, Fanconi anemia, or Li-Fraumeni syndrome
• Genetic counseling can help assess individual risk factors, provide information about hereditary conditions, and guide decision-making regarding preventive measures

Regular health check-ups:

• Attend regular health check-ups and screenings to monitor overall health, detect any abnormalities early, and address potential risk factors promptly
• Discuss personal and family medical history with healthcare providers to identify any factors that may increase AML risk

Environmental awareness:

• Stay informed about environmental factors and potential carcinogens in the surrounding environment, such as air pollution, industrial emissions, and water contaminants
• Advocate for policies and initiatives that promote environmental protection and reduce exposure to harmful substances

What is the Prognosis of Acute Myeloid Leukemia? (Outcomes/Resolutions)

The prognosis of Acute Myeloid Leukemia (AML) can vary widely depending on several factors.

Overall survival rates:

• The prognosis for AML is influenced by factors such as age, overall health, genetic abnormalities, response to treatment, and the presence of additional complications or comorbidities
• Overall survival rates for AML have improved in recent years due to advances in treatment options and supportive care measures

Age as a prognostic factor:

• Younger age at diagnosis is generally associated with better outcomes in AML
• Children and younger adults tend to have higher remission rates and overall survival compared to older adults, especially those over the age of 60 or 65

Genetic risk profile:

• Genetic mutations and chromosomal abnormalities play a significant role in determining AML prognosis
• Favorable genetic features, such as the absence of certain high-risk mutations or the presence of favorable cytogenetics like inv(16) or t(8;21), are associated with better responses to treatment and improved outcomes

Response to treatment:

• Achieving complete remission (no evidence of leukemia cells in the bone marrow) after induction chemotherapy is a positive prognostic factor
• Patients who respond well to initial treatment and proceed to consolidation therapy have a higher likelihood of long-term remission and improved survival

High-risk features:

• High-risk genetic mutations, such as FLT3-ITD, TP53 mutations, and complex karyotype abnormalities, are associated with poorer outcomes and higher rates of relapse
• Patients with high-risk AML may require more intensive treatment approaches, including stem cell transplantation, to achieve durable remission

Relapse and recurrence:

• The risk of AML relapse after achieving remission varies depending on factors such as genetic risk profile, response to initial therapy, and type of treatment received
• Early relapse within months of completing treatment is associated with a poorer prognosis compared to late relapse

Transplantation as a treatment option:

• Allogeneic stem cell transplantation (SCT) can offer curative potential for eligible AML patients, especially those with high-risk features or relapsed/refractory disease
• The success of SCT depends on factors such as donor compatibility, disease status at transplantation, and post-transplant complications

Supportive care and symptom management:

• Optimal supportive care measures, including infection prevention, blood transfusions, and management of treatment-related side effects, contribute to improved outcomes and quality of life for AML patients
• Addressing psychosocial needs and providing comprehensive supportive care throughout the treatment journey are essential for overall well-being

Advancements in treatment:

• Ongoing research and advancements in AML treatment, including targeted therapies, immunotherapy approaches, and precision medicine, hold promise for improving outcomes and survival rates
• Clinical trials and personalized treatment strategies based on individual patient characteristics are important avenues for further improving AML prognosis

Additional and Relevant Useful Information for Acute Myeloid Leukemia:

Minimal residual disease (MRD) monitoring: MRD refers to the small number of leukemia cells that may remain in the body after treatment. Monitoring MRD levels through sensitive laboratory tests, such as flow cytometry and polymerase chain reaction (PCR), helps assess treatment response and predict the risk of relapse in AML patients.