Diagnosing acute myeloid leukaemia requires a combination of blood tests, bone marrow examination, and genetic analysis to confirm the disease and guide treatment decisions.

Introduction: When to Seek Diagnostic Testing

People who should consider diagnostic testing for acute myeloid leukaemia, also called AML, are those experiencing symptoms that persist or worsen over time. Early on, symptoms may feel similar to having a cold or flu that simply won’t go away. Because AML is an aggressive cancer, these symptoms can develop and intensify quite rapidly, making timely medical attention important.^[2]

Anyone experiencing ongoing symptoms such as unusual tiredness, frequent infections that don’t respond to treatment, easy bruising or bleeding without clear cause, unexplained fever, or weight loss should speak with their doctor. While these symptoms are common to many less serious conditions, they warrant proper investigation to rule out blood cancers like AML.^[4]

People at higher risk may need to be more vigilant about seeking diagnostics. This includes individuals who have previously undergone chemotherapy or radiation therapy for another cancer, those who smoke (especially after age 60), people with a history of blood disorders such as myelodysplastic syndromes, and those exposed to certain chemicals like benzene. However, most people diagnosed with AML have no identifiable risk factors, and the condition can appear in anyone, although it is most commonly diagnosed in people over 60 years of age.^[6]

It’s also worth noting that some people are diagnosed without having any noticeable symptoms at all. AML can sometimes be detected during routine blood tests performed for unrelated reasons. This is why regular health check-ups can be valuable, as they may catch abnormalities before symptoms become severe.^[2]

Classic Diagnostic Methods for Identifying AML

When a doctor suspects acute myeloid leukaemia, the diagnostic process typically begins with a physical examination and a thorough review of the person’s medical history. During the exam, the doctor will look for signs such as pale skin, bruising, bleeding in the mouth or gums, infections, or swollen lymph nodes. These physical findings, combined with the patient’s symptoms, help guide the next steps in testing.^[14]

Blood Tests

The first laboratory test is usually a complete blood count, often abbreviated as CBC. This test measures the number of different types of cells in a blood sample, including red blood cells, white blood cells, and platelets. In people with AML, the results often show abnormal levels: there may be too many or too few white blood cells, not enough red blood cells (leading to anaemia), and not enough platelets (which help blood clot).^[14]

Another key finding in blood tests is the presence of myeloblasts, which are immature white blood cells. Normally, these cells are not found circulating in the blood because they should remain in the bone marrow until they mature. However, in AML, these abnormal blast cells can appear in the bloodstream, which is a strong indicator of leukaemia.^[6]

Bone Marrow Examination

Even if blood tests suggest leukaemia, doctors need to examine the bone marrow to confirm the diagnosis and understand the specific type of AML. The bone marrow is the soft, spongy tissue inside bones where blood cells are produced. Two procedures are typically performed together: bone marrow aspiration and bone marrow biopsy.^[14]

During bone marrow aspiration, a thin needle is used to remove a small amount of liquid bone marrow, usually from a spot in the back of the hip bone. A bone marrow biopsy involves removing a small piece of bone tissue along with the enclosed marrow. Both samples are sent to a laboratory where specialists examine them under a microscope to look for leukaemia cells and determine how many blast cells are present.^[14]

A diagnosis of AML is typically confirmed when more than 20% of the cells in the bone marrow are blast cells. The appearance of these cells, along with other features, helps doctors classify the specific subtype of AML, which is important for planning treatment.^[3]

Genetic and Molecular Testing

Modern AML diagnosis goes beyond simply counting cells. Doctors also look for specific genetic and chromosomal changes within the leukaemia cells. These tests examine the DNA of the cancer cells to identify mutations in certain genes or abnormalities in chromosomes. These findings are crucial because they help predict how the disease will behave and how well it might respond to treatment.^[2]

For example, one common genetic finding is a change where parts of chromosomes 15 and 17 switch places. This specific genetic abnormality defines a subtype called acute promyelocytic leukaemia, or APL, which requires different treatment from other forms of AML.^[6]

Understanding the genetic profile of AML cells allows doctors to classify the disease into risk groups. Some genetic changes indicate a more favourable outlook, while others suggest the disease will be harder to treat. This information directly influences treatment decisions and helps doctors provide more accurate information about what to expect.^[3]

Additional Testing to Check for Spread

Once AML is diagnosed, doctors may perform additional tests to determine whether the leukaemia has spread beyond the blood and bone marrow. Although AML primarily affects the blood and bone marrow, the leukaemia cells can sometimes spread to other parts of the body, including the central nervous system (brain and spinal cord), skin, or gums.^[6]

A lumbar puncture, also known as a spinal tap, may be performed to collect and test cerebrospinal fluid from around the spinal cord. This test checks whether leukaemia cells have reached the central nervous system. During this procedure, a needle is inserted into the lower back to collect a small amount of fluid for examination.^[14]

Imaging tests such as chest X-rays, CT scans (computed tomography), or ultrasound may also be used to look for signs of leukaemia in organs or to identify any solid tumours formed by leukaemia cells. These tumours, called myeloid sarcomas, are rare but can occur in people with AML.^[6]

Flow Cytometry and Other Laboratory Techniques

Laboratories use sophisticated techniques to analyse blood and bone marrow samples in detail. One important method is called flow cytometry, which uses special markers to identify and count different types of cells. This technique can detect even small numbers of leukaemia cells and is particularly useful for monitoring how well treatment is working.^[3]

Another technique called polymerase chain reaction, or PCR, can detect genetic material from leukaemia cells with extreme sensitivity. These advanced tests allow doctors to find tiny amounts of disease that might remain after treatment, even when standard microscope examination shows the bone marrow looks normal. This is called measurable residual disease, or MRD, and detecting it helps doctors adjust treatment plans if needed.^[16]

Diagnostic Testing for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or compare different treatment approaches for AML. People who participate in clinical trials often gain access to the newest therapies before they become widely available. However, not everyone with AML qualifies for every clinical trial, as studies have specific requirements to ensure the safety of participants and the reliability of results.^[7]

To determine whether someone is eligible for a particular clinical trial, doctors use many of the same diagnostic tests described earlier, but they look at the results in very specific ways. Each clinical trial has what are called inclusion and exclusion criteria—detailed requirements about who can and cannot participate based on their test results, overall health, and other factors.

Blood and Bone Marrow Assessment for Trials

Clinical trials for AML typically require confirmation of the diagnosis through blood and bone marrow testing. The percentage of blast cells in the bone marrow is often a key criterion. Some trials may specifically seek participants with newly diagnosed AML who haven’t yet received treatment, while others may focus on people whose disease has come back after initial treatment (called relapse) or hasn’t responded to standard therapy (called refractory disease).^[3]

Trials may also require specific blood cell counts at the time of enrolment. For example, a trial might only accept participants whose white blood cell count, red blood cell count, or platelet count falls within certain ranges. These requirements help ensure that participants are healthy enough to tolerate the experimental treatment and that researchers can accurately measure its effects.

Genetic and Molecular Profiling Requirements

Many modern clinical trials for AML focus on treatments that target specific genetic mutations or chromosomal abnormalities. For these trials, detailed genetic testing of the leukaemia cells is essential. Doctors must identify whether the participant’s AML has the particular genetic features that the experimental treatment is designed to target.^[3]

For instance, a trial might test a new drug designed specifically for AML with mutations in a gene called NPM1, or for AML with certain chromosomal changes. Participants would need to have genetic test results showing these specific features to qualify. This approach, called precision medicine or personalised medicine, aims to match patients with treatments most likely to work for their specific type of AML.

Assessment of Overall Health and Organ Function

Beyond confirming the AML diagnosis and its characteristics, clinical trials also require assessment of a person’s overall health and how well their organs are functioning. This typically involves blood tests to check kidney and liver function, as many cancer treatments are processed through these organs. People with severely impaired kidney or liver function might not be able to safely participate in certain trials.^[7]

Heart function is another important consideration, as some AML treatments can affect the heart. Tests such as an electrocardiogram (ECG or EKG), which records the electrical activity of the heart, or an echocardiogram, which uses ultrasound to create images of the heart, may be required before someone can join a trial.^[14]

Additionally, trials often use a system called performance status to measure how well someone can carry out daily activities. This helps researchers assess whether participants are strong enough to undergo the study treatment. The evaluation considers factors like whether the person spends most of the day in bed, needs assistance with self-care, or is able to work and carry on normal activities.

Testing for Measurable Residual Disease

Some clinical trials specifically enrol people who have achieved a complete remission, meaning their blood counts have returned to normal and less than 5% of bone marrow cells are blast cells. However, these trials may use highly sensitive tests to look for measurable residual disease—tiny numbers of leukaemia cells that can’t be seen with standard microscope examination but can be detected with techniques like flow cytometry or PCR.^[16]

Studies focusing on MRD-positive patients aim to develop treatments that can eliminate these remaining cells and reduce the chance of the disease coming back. Qualifying for these trials requires the advanced testing capabilities to detect and measure residual disease accurately.

Monitoring and Follow-up Testing in Clinical Trials

Once enrolled in a clinical trial, participants undergo regular monitoring to track how they respond to treatment and watch for any side effects. This involves repeated blood tests, bone marrow examinations at specific time points, and other assessments as outlined in the study protocol. These tests serve dual purposes: ensuring participant safety and gathering data about the experimental treatment’s effectiveness.^[16]

The frequency and type of monitoring tests in a clinical trial are often more intensive than in standard care. Participants should expect more frequent hospital or clinic visits and more regular blood draws. This level of monitoring is necessary to carefully evaluate new treatments and understand exactly how they work in the body.