What is Acute Myeloid Leukemia?
Acute myeloid leukemia (AML) is a fast-growing type of blood cancer that occurs when immature blood cells known as “blasts” excessively grow in the blood and bone marrow. This rapid growth of cells affects the efficient production of red blood cells and platelets, and consequently leads to bone marrow failure faster than in slower-moving types of leukemia.
While an intense combo of chemotherapy drugs can sometimes completely clear the body from this type of leukemia, the only surefire cure is a stem cell transplant from a donor. However, despite advancements in treatment, the overall outlook, especially for older people, remains less than ideal.
What Causes Acute Myeloid Leukemia?
The European LeukemiaNet’s 2022 recommendations are an important guide for understanding and classifying a type of blood cancer called acute myeloid leukaemia (AML) based on the specific mutations present. But before health professionals can effectively use this guide, they need to understand the origins and pathways of the disease.
For instance, patients with myelodysplastic syndrome (MDS) – a group of disorders causing a drop in healthy blood cells, they are at higher risk of developing AML. Patients with MDS need close monitoring because of their greater danger.
Another group of patients potentially progressing into AML are those with myeloproliferative neoplasms, which refers to several conditions causing overproduction of blood cells. This includes conditions like myelofibrosis, essential thrombocythemia, polycythemia vera, and chronic myeloid leukemia. Signs of this transition can vary but often include drops in blood count alongside increases in immature blood cells, called blasts. Conditions like MDS and myeloproliferative neoplasms, along with other diseases such as aplastic anemia, can lead to secondary AML.
Patients who have previously undergone chemotherapy for other cancers also possess a higher risk for AML. For example, those exposed to certain types of chemotherapy or radiation might develop MDS or AML with specific chromosome abnormalities usually 5-7 years after treatment. Certain types of chemotherapy medicines can also lead to AML, characterized by a specific genetic rearrangement. These outcomes are typically referred to as therapy-related MDS or AML.
Other factors like radiation, smoking, and exposure to a chemical called benzene can also increase the risk of AML. However, despite knowing these risk factors, most AML cases still occur spontaneously without a known cause.
Risk Factors and Frequency for Acute Myeloid Leukemia
Every year, about 4.3 out of every 100,000 people in both the male and female population are diagnosed with this condition, adding up to over 20,000 new cases in the United States. The middlemost age at diagnosis is around 68, and it’s more commonly seen in non-Hispanic Whites. Also, it’s more prevalent in males compared to females, with the ratio being approximately 5 males to 3 females.
Signs and Symptoms of Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a condition where the body produces too many abnormal white blood cells. This issue impacts the creation of healthy blood cells leading to several symptoms. These symptoms may appear quickly, typically within a few days or weeks.
- Frequent illnesses due to a poor immune system
- Anemia or lack of red blood cells
- Easily getting bruises
- Severe bleeding
- Headaches
- Bone pain
- General feeling of weakness
- Constant fatigue
- Shortness of breath
- Tightness in the chest
Some patients may exhibit physical signs that medical professionals will look for. These can include pale skin, bruises, and an enlarged liver or spleen. Although swollen lymph nodes are not commonly seen in AML patients, skin lesions and symptoms of a condition called Disseminated Intravascular Coagulation (DIC), which causes problem with the body’s blood clotting process, might be present. Signs of DIC can include bleeding gums, purple spots on the skin, tiny red or purple dots on the body, and bleeding from the injecting sites in hospitals.
Testing for Acute Myeloid Leukemia
If someone is showing symptoms like unexpectedly low levels of white blood cells, hemoglobin, or platelets, easy bruising or bleeding, frequent infections, or even kidney failure, it might mean they have Acute Myeloid Leukemia (AML). Kidney failure can occur due to auto-tumor lysis syndrome (auto-TLS), a situation where the body starts destroying its own tumor cells. Even without prior chemotherapy, this can be considered a medical emergency.
Lab tests revealing high levels of LDH (a type of enzyme), uric acid, potassium, and phosphorus can be an indication of auto-tumor lysis due to rapid cancer cell decay.
When these symptoms are present, a simple blood smear test can provide important information. Blood samples might show a significant drop in platelets, the presence of immature white blood cells called blasts, and maybe even cell fragments called schistocytes which can signify clotting disorders.
A particular form of AML, acute promyelocytic leukemia (APL), shows distinctive clumps of granules in the cytoplasm of the cells known as Auer rods. If a blood test reveals blasts making up 20% or more of the cells present, it’s a sure sign of AML.
It’s important to involve specialists when AML is suspected to confirm the diagnosis.
Certain emergencies like neurological impairment and breathing difficulties can occur due to the effects of AML. Following a confirmed AML diagnosis, patients are advised to have an electrocardiogram (ECG) and a 2-dimensional (2D) echocardiogram in preparation for potential heart-related side effects from therapies, such as those using anthracyclines.
Treatment Options for Acute Myeloid Leukemia
The treatments used for acute myeloid leukemia (AML) can damage the bone marrow and cause other health problems, such as low blood counts and kidney failure. These treatments can also lead to imbalances in blood electrolytes, so it’s essential to monitor heart health through tests like ultrasound, ECG, and telemetry throughout the therapy process. It’s also important to keep a close eye on things like body temperature in a specialized oncology unit, as white blood cell recovery can take up to four weeks, during which the patient may develop a fever due to reduced immune function.
Before starting treatment, it’s crucial to involve bone marrow transplant specialists for patients with medium to high risk according to certain criteria. A type of bone marrow transplant, known as allogeneic hematopoietic stem cell transplantation (HSCT), is the only treatment for AML that has a chance of curing the disease. This should be considered for any high or medium-risk patient who reaches complete remission from their disease.
The standard treatment for AML, known as induction therapy, doesn’t merely depend on the patient’s age. For younger patients who are considered healthy and have a type of AML without multiple or high-risk features, the typical treatment plan is a “7+3” protocol. This consists of cytarabine infusion for seven days and anthracycline administration for three days. For patients with more complex or high-risk AML, a different regimen called FLAG is often used. In older patients and those who are fit for treatment, a cocktail of drugs known as a hypomethylating agent and venetoclax is often used.
If adults are not considered fit for these treatments, they can be given care that focuses on comfort and symptom management. If the patient achieves remission from their disease, the combination of the hypomethylating agent and venetoclax can be continued indefinitely. However, the doctor should balance the risks and benefits of the long-term treatment alongside the patient and their family. If the patient is suspected to have APL, a specific type of AML, the treatment should focus on managing it with all-trans retinoic acid (ATRA). Confirmation of diagnosis should be made through certain lab tests. If the WBC count exceeds a certain threshold, full therapy should not start until the diagnosis is confirmed.
For younger, fit patients receiving induction therapy, a bone marrow biopsy should ideally be performed after therapy when the neutrophil and platelet counts recover to a certain level. In these patients, complete remission is considered if the bone marrow shows no signs of leukemia with less than 5% blasts by aspirate differential. In older patients going through induction therapy with venetoclax and a hypomethylating agent, the initial bone marrow biopsy is typically conducted after at least two complete cycles of therapy, each lasting 28 days.
After achieving complete response with optimal induction therapy, residual disease often remains. Therefore, additional therapy, known as consolidation therapy, is needed to reduce the risk of a relapse. This therapy aims to eliminate any residual disease. In patients who have received 7+3 induction therapy, consolidation therapy involves a high dose of cytarabine. Those who received FLAG therapy during induction should have additional cycles of the same regimen during consolidation. Similarly, all intermediate or high-risk patients, who are otherwise suitable, should be offered allogeneic HSCT to reach a complete remission.
For patients whose AML has relapsed, several treatments are available depending on the specific mutations identified in their cells. These treatments aim to achieve higher remission rates than traditional chemotherapy. Hospitalized patients with the FLT3-ITD mutation can receive sorafenib as a maintenance therapy after transplantation.
All blood products given must be irradiated to prevent a severe complication known as transfusion-related graft versus host disease.
What else can Acute Myeloid Leukemia be?
There are other health conditions that can appear very much like Acute Myeloid Leukemia (AML). They include:
- Acute Lymphoblastic Leukemia (a type of cancer that affects white blood cells)
- Anemia (a condition characterized by lack of red blood cells)
- Aplastic Anemia (when the body stops producing enough new blood cells)
- B-cell Lymphoma (a type of cancer that begins in the lymphatic system)
- Bone Marrow Failure (when the marrow stops making enough healthy blood cells)
- Chronic Myelogenous Leukemia (a cancer of the white blood cells)
- Lymphoblastic Lymphoma (a fast-growing cancer of a type of white blood cells called lymphocytes)
- Myelodysplastic Syndromes (group of disorders caused by poorly formed or dysfunctional blood cells)
- Myelophthisic Anemia (a type of anemia caused by the displacement of the blood-making cells in the bone marrow)
- Primary Myelofibrosis (a rare bone marrow cancer)
It’s crucial for medical professionals to correctly diagnose the specific condition to ensure the appropriate treatment is given.
What to expect with Acute Myeloid Leukemia
The chance of recovery from AML (a type of blood cancer) depends on factors unique to each patient, like their genetic makeup. For example, a patient has a better chance of recovery if their AML is associated with certain changes in their chromosomes, specifically t(8;21), t(15;17), and flipped chromosome 16, or t(16;16).
However, other genetic changes, such as t(6;9)(p23.3;q34.1) or mutations in genes called ASXL1 and U2AF1, give a less promising outlook. The outlook can be less favorable for older individuals, those with an extremely high white blood cell count at diagnosis, those who’ve had AML due to previous treatment for another cancer, and those with cancer cells present in their brain or spinal cord.
Modern techniques, like PCR and flow cytometry, can help doctors identify tiny amounts of disease left behind even after a patient reaches full remission. If a patient with certain chromosomal changes (t(8;21) AML) still shows an elevated level of specific gene products (RUNX1-RUNX1T1) despite therapy, their likelihood to face a relapse is higher.
