How Highly Sensitive Genetic Testing Can Help Shape AML Treatment Decisions

A highly sensitive test that measures very small amounts of a genetic mutation called FLT3-ITD for people with acute myeloid leukemia (AML) could help guide treatment decisions and determine prognosis. New research presented at the 2025 American Society of Hematology (ASH) conference compares FLT3-ITD-positive AML patients with those who expressed very small amounts of FLT3-ITD. 

What is FLT3-ITD-positive AML?

FLT3-ITD is a genetic mutation found in some people with AML. FLT3 is a gene that helps control how blood cells grow, reproduce, and divide. When a change called an internal tandem duplication (ITD) occurs on this gene, leukemia cells grow and divide too quickly. Mutations to the FLT3 gene are associated with poor outcomes among people with acute myeloid leukemia (AML) and may require more aggressive treatment.  

AML is considered FLT3-ITD-positive if a certain amount of mutated cells are found in the bone marrow. In 2022, the European LeukemiaNet (ELN) published new recommendations for the treatment of AML that included updates to genetic risk classifications. The guidelines classify cases of AML with FLT3-ITD mutations as intermediate risk. Classifying AML into separate risk categories helps to inform prognosis, whether a stem cell transplant is feasible, and treatment pathways.  

FLT3-ITD-positive AML is treated with a combination of chemotherapy and an FLT3 inhibitor. FLT3 inhibitors target the mutated FLT3 gene and helps to reduce the growth of AML cells. 

Some people express very small amounts of cells with the FLT3-ITD mutation. They do not express enough FLT3-ITD to be considered FLT3-ITD-positive, but still have small, measurable amounts called microclones. Researchers have wondered if these small amounts of FLT3-ITD could help predict prognosis and guide treatment decisions. 

Comparing FLT-ITD-positive AML with AML with the presence of FLT-ITD microclones

A recent study presented at the ASH Annual Meeting compared outcomes among people with FLT3-ITD-positive AML versus those of people with lower levels of FLT3-ITD. 

The study included 212 patients (32%) with microclones, or low levels of the mutation. It included 446 patients (68%) with higher levels of the mutation.     

Most study participants (76%) received intensive chemotherapy. Others were managed with less intensive treatments because they were unable to receive the intensive chemotherapy due to other health challenges. 

Researchers looked at complete response (CR), a measure that shows there are no remaining cancer cells present on standard tests. 

For the people with higher levels of FLT3-ITD who were treated with intensive treatment, the CR was 88% compared to 74% among those with lower levels. 

The study showed that the following factors were associated with achieving CR:

• Younger age
• Presence of certain gene changes (NMP1)
• Absence of certain gene changes (DNMT3A and MR)
• A high level of FLT3-ITD 
• Being classified as favorable or intermediate risk on the ELN risk scale

Another measure, overall survival, or how long a person survives after treatment, was 58% after 3 years among patients who received intensive treatment.

It is important to note that factors like older age and higher white blood cell counts made a significant impact on prognosis and were more likely to lead to worse outcomes. 

Additionally, relapse or return of disease symptoms occurred in 27% of people at a median of 8 months. After three years, fewer than half of the study participants were disease-free after being treated. 

This highlights that even after receiving intensive therapy, microclones can survive treatment and lead to relapse.

What this means for patients

For now, if low levels of FLT3-ITD are found during genetic testing, it could help doctors predict prognosis and plan treatment. More research is needed to more fully understand whether people with low-level FLT3-ITD would benefit from treatment with FLT3-ITD inhibitors. 

Studying genetic mutations and how they respond to different treatments can help researchers better understand AML and prognosis. These types of studies emphasize the importance of sensitive testing and targeted therapies and the impact they can have on outcomes for people with AML. 

Questions to ask your care team

Consider asking these questions about your AML diagnosis: 

• What type of genetic testing will I receive?
• Do I have FLT3-ITD-positive AML?
• Were low levels of FL53-ITD found during testing?
• What does this mean for my prognosis or treatment?

Connect your records

When you securely connect your records to the HealthTree Cure Hub, all of your health information is in one place. You can monitor your labs, see out of range values, and also learn about what has worked for others with AML. Additionally, researchers can use the anonymized data in the portal to make important scientific discoveries that can help improve treatment and ultimately lead to cures. Follow the link below to connect your records.

Connect Your Records

Sources: 

• Diagnostic evaluation methods and prognostic impact of FLT3-ITD microclones in AML 
• HealthTree What are FLT3 Inhibitors, and How are They Used in AML?
• 2022 ELN recommendations for the diagnosis of AML in adults