AML is an aggressive condition of the bone marrow and may be life-threatening if left untreated. The risk increases with age, and men have a higher risk than women. The disease is classified based on various systems. Almost 50% of the patients who achieve remission may have a recurrence.
Acute myeloid leukemia, which is often called AML blood cancer, is a cancer affecting the bone marrow and blood. Patients with AML rapidly develop abnormal blood cells, i.e., platelets, red blood cells, and white blood cells. The origin of AML is in the myeloid cells that are responsible for the production of blood cells. Symptoms include frequent infections, shortness of breath, and bleeding. Diagnosis of the condition is through bone marrow and blood testing. However, other methods, such as imaging tests, may also be used to detect the involvement of other organs, especially in the final stages of acute myeloid leukemia. The prognosis of AML depends on several factors, including the type of AML, overall health, and the patient's response to treatment. AML cancer treatment involves chemotherapy, radiation therapy, and targeted therapy.
Acute myeloid leukemia is a relatively rare type of leukemia compared to other chronic types of leukemia. The risk of this disease increases with age, and men are at higher risk for AML compared to women. The incidence varies with geographical location. Further, there is an increasing proportion of AML among different types of leukemia. For instance, the ratio for AML was 18% of total leukemia cases globally. It increased to 23% in the year 2017. In India, the annual incidence is 2-3 per 100,000. AML in India is less than 1/100,000 < 30 years of age and 17/100,000 by 75 years. It accounts for < 10% of all leukemia cases in children aged <10 years and 25-30% in people aged between 10 and 15 years.
There are several methods for classifying AML. The World Health Organization system, updated in 2016, classifies AML into the following types of acute myeloid leukemia:
The following are the different stages of acute myeloid leukemia:
Untreated AML disease is a newly diagnosed disease, and the patients have not undergone any treatment. The disease is characterized by a few blood cells, i.e., platelets, red blood cells, and white blood cells. The blood sample contains immature cells, also known as blasts. In cases where leukemia is diagnosed, these blast cells are known as leukemia cells. Patients have ≥20% of the cells as blast cells in the bone marrow.
This stage is characterized by the presence of at least 5% of the cells in the bone marrow as blast cells. This stage may occur during treatment or when the cancer recurs after treatment completion.
This stage is characterized by the presence of at least 5% of the cells in the bone marrow as blast cells. This stage may occur during treatment or when the cancer recurs after treatment completion.
Remission may be divided into complete remission and particle remission. Complete remission is characterized by a platelet count greater than 100 x 109/L and a neutrophil count greater than 1 x 109/L without blood transfusion, the presence of less than 5% blast cells in the bone marrow, no AML symptoms, such as fatigue, weight loss, and fever, and the absence of any signs and symptoms of leukemia in the spinal cord and brain. Partial remission occurs when the patients have less than 2% of the bone marrow cells as blast cells and there is normal bone marrow functioning.
Leukemia cells can be identified through conventional laboratory tests, such as microscopy, and highly sensitive tests, e.g., polymerase chain reaction and flow cytometry. After the AML cancer treatment, some leukemia cells are still present in the blood. However, these cells are not identified with conventional laboratory tests but can be detected through highly sensitive techniques. AML identified through highly sensitive techniques but not through traditional techniques is known as measurable residual disease or minimal residual disease. It assists clinicians in determining the response to treatment and predicts the risk of cancer recurrence.
Relapsed AML is when the cancer recurs after remission or complete treatment. Relapsed AML is characterized by at least 5% of the bone marrow cells being blast cells, and the proportion of blast cells continues to rise.
Refractory AML is when the AML does not respond to the available treatment even after intensification. The patients are said to have refractory AML if they fail to achieve complete remission after a couple of cycles of induction chemotherapy.
Patients with AML have multiple symptoms with varying severity based on the degree of anemia. Various acute myeloid leukemia causes exist, some of which are modifiable. Identifying the causes and preventing them is important to reduce the occurrence of AML.
Acute myeloid leukemia (AML) may occur in any individual. However, certain population groups are more vulnerable to AML compared to other population groups. Adults ≥65 years of age are at higher risk of developing AML compared to those <65 years of age. Men are at higher risk of developing AML. People exposed to harmful radiation (nuclear reactor accidents), toxic chemicals (benzene), and those who smoke are more commonly affected by AML. Individuals with a history of radiation therapy or chemotherapy, underlying medical conditions, such as myelofibrosis, myelodysplasia, thrombocythemia, and polycythemia vera, and genetic conditions, such as Down syndrome, have a higher risk for AML.
The signs and symptoms of myeloid leukemia may vary from one patient to another. Following are some of the common acute myeloid leukemia symptoms:
Fever is a common acute myeloid leukemia symptom and may be due to various reasons. Leukemia cells have the potential to raise the body temperature. Most cases of fever in patients with AML are due to infection, as AML reduces the strength of the immune system and makes the patient vulnerable to infection.
Bone pain is another common acute myeloid leukemia symptom. Bone pain in patients with AML is due to various reasons. These include infiltration into bone marrow, bone marrow expansion, microscopic fractures due to weak bones, infection, and the effect of leukemia cells on the muscles.
Patients with AML also experience fatigue. Patients with AML have abnormal cells that displace the healthy cells. These patients have low levels of red blood cells, which are responsible for carrying oxygen to different tissues. Infection in these patients also imparts an excessive burden on the body. In addition, the body is also fighting against cancer, thereby consuming energy. Fatigue is also the result of emotional and psychological stress due to the disease.
Shortness of breath may also be an acute myeloid leukemia symptom. It may be for various reasons. Anemia reduces oxygen delivery to the tissues. Lack of oxygen in the tissues may lead to shortness of breath. Infections, particularly respiratory tract infections, also result in shortness of breath. The other causes of shortness of breath include infiltration of leukemia cells in the pulmonary system and fluid accumulation in the lungs in the advanced stages of the disease.
The red tint of the skin is due to the optimal level of red blood cells in the blood. However, patients with AML have reduced levels of red blood cells. Thus, the skin of patients with AML looks pale.
Healthy white blood cells fight against pathogens to protect the body from infection. However, in patients with AML, healthy white blood cells are produced in less quantity, making the patients more vulnerable to infection. In addition, chemotherapy in these patients also lowers the number of healthy white blood cells.
The burning sensation is not a common acute myeloid leukemia symptom. It may be because of inflammation, infection, or bone pain. In addition, a burning sensation may also be due to chemotherapy in this patient population.
Frequent nosebleeds in patients with AML are primarily due to thrombocytopenia (low platelet count) due to the disease itself and chemotherapy. In some cases, the mucosal membrane of the nose may also be affected by AML cells, resulting in nosebleeds.
Bleeding gums are also an acute myeloid leukemia symptom, especially in cases where the patients have significantly low levels of platelets. Leukemia cells may also infiltrate the mucosal layer of the gums, resulting in bleeding.
Some of the common acute myeloid leukemia causes include:
Smoking is a common acute myeloid leukemia cause. AML due to smoking occurs because of chronic exposure to benzene and other harmful chemicals present in cigarette smoke.
Exposure to harmful chemicals is also an acute myeloid leukemia cause. Individuals exposed to benzene for a significant period of time may develop AML.
Chemotherapy drugs, such as alkylating agents, are also acute myeloid leukemia causes. In many cases, myelodysplastic syndrome is followed by AML.
High doses of radiation, such as due to nuclear reactor accidents or radiation therapy for other cancers, could also serve as an acute myeloid leukemia cause.
Myeloproliferative disorders, such as polycythemia vera, are also acute myeloid leukemia causes. Other disorders that may cause AML include myelofibrosis and thrombocythemia.
People with a family history of AML have a higher risk of developing AML compared to people who do not have a family history of AML.
Genetic conditions, such as Down syndrome, trisomy 8, neurofibromatosis type 1, and Li-Fraumeni syndrome, are also acute myeloid leukemia causes.
If the patients experience fever, pain, fatigue, easy bruising, bleeding from the nose or gums, frequent infections, and shortness of breath, they should consult an oncologist.
Multiple advanced approaches are available for acute myeloid leukemia diagnosis and treatment. Usually, a combinatorial approach is implemented for the effective management of the condition. Acute myeloid leukemia treatment interventions are prescribed based on the type of AML, the patient’s age, and overall health.
The following are the important procedures recommended for an accurate acute myeloid leukemia diagnosis:
Although blood tests may not be enough for the definitive diagnosis of acute myeloid leukemia (AML), they may provide detailed information about the overall health of the patients. Various types of AML diagnosis blood tests are conducted on an individual suspected of AML.
A complete blood count (CBC) determines the number of different types of blood cells, i.e., red blood cells, white blood cells, and platelets. In patients with AML, there is an increase in the number of abnormal cells.
Clinicians may also advise the patient to undergo peripheral blood smear tests. The test involves the examination of blood cells under the microscope.
The doctor may also recommend the patient undergo kidney function tests and liver function tests to determine the health status of these organs. The patients may also undergo chemical analysis of the blood to check the levels of electrolytes.
Sometimes, in AML patients, the blood clotting ability may be affected. Thus, the patient may also be advised to undergo tests to determine activated partial thromboplastin time and prothrombin time.
Bone marrow aspiration and biopsy are the important tests conducted in patients suspected of having AML. These tests are performed for a definitive acute myeloid leukemia diagnosis. Bone marrow aspiration and biopsy provide detailed information about the bone marrow cells and help confirm leukemia and its subtypes. Both aspiration and biopsy involve obtaining bone marrow samples. In aspiration, the clinicians obtain the liquid bone marrow sample through a thin, hollow needle. A relatively larger needle is used to withdraw solid tissue from the bone marrow during a biopsy. These samples are further examined under a microscope for the presence of cancer cells.
The biomarker test is an important test for acute myeloid leukemia diagnosis. These tests help in the identification of the molecular and genetic characteristics of the leukemia cells. Biomarker tests help in risk stratification to determine the AML leukemia prognosis. These tests also help develop optimal treatment strategies, as certain mutations may influence the treatment choice. The tests are also helpful in monitoring minimal residual disease (MRD) to evaluate treatment efficacy.
Immunohistochemistry is the technique that determines the presence of specific proteins in the tissue under analysis by using antibodies to bind to target proteins. Although immunohistochemistry is generally used for solid tumors, it is sometimes used in certain cases for diagnosing and characterizing AML, especially while evaluating biopsy samples. Immunohistochemistry helps identify different types of cells present in the bone marrow. It also provides vital information about the type of AML and the presence of abnormal antigen expression. This information assists in characterizing the disease and has prognostic implications.
This technique involves the analysis of the chemical and physical characteristics of leukemia cells in a fluid by passing it under a laser beam. Through this technique, the specialists assess the immunophenotype of malignant cells and identify specific markers on the cell surface. Flow cytometry also determines blast percentage (blast cells in bone marrow), identifies aberrant antigen expression, and monitors minimal residual disease (to analyze treatment efficacy).
Cytogenetics is the technique used to detect changes in the chromosomes in leukemia cells. The technique looks for broken, rearranged, missing, or extra chromosomes. Cytogenetic testing in acute myeloid leukemia diagnosis examines the structure of the chromosomes along with their numbers. There is an association between specific chromosomal abnormalities and different AML subtypes. For instance, inv (16), t (8;21), or t (15;17) translocations are associated with different AML subtypes.
Molecular testing is a method for acute myeloid leukemia diagnosis that provides information about genetic mutations in leukemia cells. Molecular testing helps determine the acute myeloid leukemia survival rate, optimizes treatment strategies, and identifies targeted therapies in certain cases of AML. The AML mutations detected by molecular testing include CEBPA mutations, FLT3 mutations, IDH1 and IDH2 mutations, TP53 mutations, and NPM1 mutations.
As AML involves the bone marrow and blood, imaging tests are not often used for acute myeloid leukemia diagnosis. However, the doctor may recommend imaging tests to assess the AML complications or to determine the involvement of various organs that may affect the treatment decisions. The type of imaging tests and their requirements depend on the symptoms and overall health status of the patient.
Computed tomography uses X-rays to obtain detailed images of the target organ. In patients diagnosed with AML through biopsy and bone marrow aspiration, a CT scan allows clinicians to determine the infiltration of leukemia cells into various organs, such as the spleen, liver, and lymph nodes. A CT scan also assists in evaluating the efficacy of the treatment by comparing the images after the treatment with baseline images.
MRI is the technique to obtain clear images with powerful magnetic fields and radio waves. It helps to detect the involvement of the brain and spinal cord in AML. MRI also assists in determining the swollen lymph nodes in the abdomen or chest due to AML. MRI improves the efficiency of acute myeloid leukemia diagnosis.
A PET scan uses radioactive sugar analogs to determine the spread of cancer to various organs. The technique helps determine the extent of the spread of AML and assists in appropriately staging the disease. It also monitors the patient’s response to the treatment given. It also assesses the minimal residual disease that may predict AML relapse.
Lumbar puncture (spinal tap) involves obtaining the cerebrospinal fluid from the spinal canal with the help of a thin needle for therapeutic and diagnostic purposes. It assists clinicians in determining the involvement of the CNS in patients with acute myeloid leukemia.
The following are some of the most effective acute myeloid leukemia treatment options:
Chemotherapy is one of the most common acute myeloid leukemia treatment modalities. Chemotherapy for acute myeloid leukemia aims to eliminate or reduce the number of leukemia cells in the blood and the bone marrow and achieve remission through cytotoxic or cytostatic drugs. Chemotherapy, in some cases, may also be used in combination with targeted therapy. Chemotherapy for acute myeloid leukemia treatment may be done through the following steps:
Remission induction therapy is a critical phase in AML treatment. This therapy aims to achieve remission by lowering the number of leukemia cells to the extent that they are not detectable under the microscope.
Once the remission is achieved with remission induction therapy, the next step is consolidation therapy. It aims to remove the remaining leukemia cells to lower the risk of relapse and increase the remission period.
Maintenance therapy aims to maintain remission and minimize the risk of relapse. In contrast to induction and consolidation therapy, not all patients with AML require maintenance therapy. The decision to initiate maintenance therapy depends upon the patient's age, overall health status, leukemia characteristics, and response to prior treatment.
Targeted therapy uses drugs that target certain pathways of molecules that are vital for the growth and proliferation of leukemia cells. Unlike traditional chemotherapy, which targets both healthy and malignant cells, targeted therapy only targets the molecules and pathways specifically in the malignant cells.
Allogeneic stem cell transplantation is a potential AML cancer treatment option for certain patients. The procedure involves the transplantation of allogeneic stem cells from a healthy donor. The procedure is performed in patients with certain genetic mutations, high-risk diseases, and relapses after initial treatment.
Radiation therapy is not a standard acute myeloid leukemia therapy and is used in certain specific situations. Oncologists recommend this therapy when patients have solid organ involvement or involvement of the central nervous system. Radiation therapy is also used in conditioning before bone marrow transplantation.
HCG is an advanced center for acute myeloid leukemia diagnosis and treatment. The center has a strong reputation for managing all types of hematological malignancies. Further, the multidisciplinary team at the center comprises oncologists, hematologists, radiation specialists, and pathologists to facilitate excellent disease management in AML patients. The center also has advanced surgical facilities to perform bone marrow transplantation.
Several factors increase the risk of acute myeloid leukemia. Some of these factors, such as smoking and carcinogen exposure, are modifiable. However, other risk factors for AML, such as genetic conditions, are non-modifiable. AML risk groups include people who smoke or have undergone cancer therapy. Acute myeloid leukemia prevention measures include quitting smoking and avoiding exposure to harmful chemicals.
Some of the common acute myeloid leukemia risk factors include:
AML may occur at any age. However, individuals over 45 are at a higher risk of developing this condition. The risk of AML increases as one grows older. Studies reported that the average age of people at diagnosis was 68 years.
Evidence suggests that there is an association between cigarette smoking and an increased risk of acute myeloid leukemia. Studies also reported a higher risk among current smokers compared with former smokers. The risk of AML increases with increased frequency and duration of smoking.
Patients treated with chemotherapy drugs for other cancers, such as breast cancer or Hodgkin’s lymphoma, are at increased risk of developing AML. This is because prolonged exposure of blood cells to these agents may cause mutations, resulting in their uncontrolled growth.
Radiation therapy is another acute myeloid leukemia risk factor. People who underwent radiation therapy as a part of a cancer treatment strategy are at higher risk of developing AML compared to those who did not undergo radiation therapy. The common AML types that may develop after radiation therapy include chronic myelogenous leukemia, acute myelogenous leukemia, and acute lymphoblastic leukemia.
Chronic exposure to certain chemicals is also one of the acute myeloid leukemia risk factors. Long-term exposure to benzene significantly increases the risk of AML. This chemical is used in various industries, including the shoe industry, the rubber industry, and oil refineries.
Certain genetic disorders are also acute myeloid leukemia risk factors. Some of them include:
Children with Down syndrome are at greater risk of developing acute megakaryoblastic leukemia. Studies have shown that children with Down syndrome have a 150 times increased risk of developing AML.
It is a genetic disorder affecting the area of the brain controlling motor movement and speech. Patients with ataxia telangiectasia have a higher chance of developing AML.
The presence of Li-Fraumeni syndrome increases the risk of various types of cancer, including AML. The other cancers associated with this syndrome include adrenal cortical tumors, brain cancer, and breast cancer.
Fanconi anemia is a condition of the bone marrow characterized by reduced production of all blood cells. Patients with this condition have an increased risk for AML.
Wiskott-Aldrich syndrome is a genetic immunodeficiency condition characterized by a compromised immune system, eczema, and a decreased ability to clot blood. Wiskott-Aldrich syndrome is an acute myeloid leukemia risk factor.
Bloom syndrome is characterized by photosensitivity, telangiectatic erythema, and severe growth retardation in the postnatal period. Patients with this syndrome have an increased risk of developing various cancers, including AML.
Patients with familial platelet disorder syndrome have abnormal platelet function, mild to moderate thrombocytopenia, and a higher risk of developing hematological malignancies, including AML.
Some of the bone marrow disorders also increase the risk of AML.
Polycythemia vera is an acute myeloid leukemia risk factor characterized by an increase in all types of blood cells, especially red blood cells.
It is a condition that causes severe scarring in the bone marrow, resulting in severe anemia. The patients experience weakness and fatigue. Myelofibrosis has the potential to transform into AML.
It is a condition characterized by the production of excessive platelets in the bone marrow. Essential thrombocytosis may progress into AML in almost 1–4% of the patients.
It is a group of cancers characterized by the inability of immature bone marrow cells to mature cells. Patients with myelodysplastic syndromes are at a higher risk of developing AML.
Aplastic anemia is an acute myeloid leukemia risk factor. It is a rare and serious disease and may occur at any age.
Some of the common acute myeloid leukemia prevention measures include:
Avoiding smoking is one of the most important acute myeloid leukemia prevention measures. Quitting smoking significantly lowers the risk of various types of cancer, including AML, as it avoids exposure to harmful chemicals present in cigarette smoke.
Several chemicals, such as benzene, increase the risk of AML. Avoiding prolonged exposure to these chemicals is another important acute myeloid leukemia prevention measure.
Acute myeloid leukemia is characterized by a low count of healthy blood cells. Patients experience weakness and fatigue and have an increased risk of infection. Classification of the types of acute myeloid leukemia may be based on the cause of acute myeloid cancer, such as genetic abnormalities or cancer therapies. Stages of AML leukemia include untreated, active, relapse, remission, and refractory.
