Like many rare cancers, acute myeloid leukemia (AML) presents a well-known challenge: a varying set of treatment guidelines. In this case, physicians have multiple, sometimes conflicting, sets of guidelines and classifications to sort through when caring for patients with AML.
To overcome this challenge, UVA Health hematology-oncologist Firas El Chaer, MD, led an effort to consolidate the AML classifications and guidelines into actionable recommendations that physicians can use in clinical settings.
The classification of AML is extremely important, El Chaer notes, as it determines how patients will be treated, their prognosis, and their eligibility for clinical trials.
“Not only are guidelines changing over time as we learn more about AML, but they are also diverging,” says El Chaer. “The benefit of our study, published by the American Society of Hematology, is that it brings together these classifications and guidelines and provides examples of how patients with common, challenging forms of AML can be treated in ways that align with all the guidelines — and for the better of the patient.”
A Brief History of AML Guideline Confusion
The first guidelines for classifying and treating AML emerged in 1967 from the World Health Organization (WHO). The WHO joined forces and continued to collaborate with the International Consensus Classification (ICC) to publish unified specifications for myeloid neoplasms, while a separate body, European LeukemiaNet (ELN), began posting its own recommendations in 2010. In 2022, the WHO separated from the ICC, resulting in three separate classification systems impacting AML.
“These classifications overlap, but there are specifics to each that make the diagnosis of blood cancers challenging and confusing,” says El Chaer. For example, newly discovered genetic mutations relevant to AML vary significantly as diagnostic indicators among the guidelines. And while measurable residual disease, a newly recognized factor impacting AML, has been incorporated into daily practice and as a prognostic indicator, it is not incorporated consistently into the daily practice.
These three documents update the “classification, risk stratification, prognostication, monitoring recommendations, and response assessment of patients with AML,” wrote El Chaer in his guidance. He noted that these changes have come with major shifts in how physicians understand and treat AML. Previously, guidelines for treating AML relied on morphology, but recent research has shown that morphology isn’t the only driver. Genetic abnormalities also play a role, which impacts treatment, prognosis, and clinical trial enrollment. Further, a greater understanding of AML biology has resulted in new therapies and novel clinical trials, which must be accounted for in treatment guidelines.
“With new research, we’re continuing to learn more about genetic abnormalities and how they can help to define AML,” El Chaer says. “Our goal is to try to direct clinicians on what these abnormalities mean and how they change treatment options for patients.”
Bringing Clarity to AML Guidelines
With these disparate systems in place, El Chaer and his colleagues recognized a need to incorporate these three guidelines into one paper to provide clear guidance to diagnose, classify, and develop treatment plans.
To create his updated guidance, El Chaer evaluated the most common, challenging, and controversial cases his team sees in the clinic and presented them from the point of view of each of the guidelines.
“It’s not just one message,” says El Chaer. “We tried our best to summarize the similarities and differences between the classifications while incorporating expert opinions in areas where there is not enough research to help clinicians determine the next steps in the management of AML.”
In addition to the cases, El Chaer wrote a letter for publication in The Lancet Haematology with recommendations for future iterations of AML-specific guidelines. These recommendations include:
- Agreeing to the need for a unified system among the WHO, ICC, and ELN
- Reengaging with the hematopathology societies in developing the guidelines and providing substantive revisions to help guide diagnosis and treatment plans
- Involving patient advocacy groups and other stakeholders
“We must engage with all the stakeholders impacted by AML and blood cancers when we’re creating these recommendations,” says El Chaer. “This way we can collaborate and provide feedback to promote a system that supports the needs and perspectives of those it serves.”
A Comprehensive Future for Treating AML
Given the challenges of treating AML, patients diagnosed with AML should be referred to an academic medical center where clinicians have numerous resources to diagnose and treat patients with the most advanced treatment options, including clinical trials.
“UVA Health has tailored clinical trials customized to each subclassification of AML,” says El Chaer. “These clinical trials are ongoing and support both children and adults with these rare cancers.”
Academic medical centers also bring together the numerous specialties and subspecialties involved in treating AML and other blood cancers, including:
- Hematology oncologists with specific expertise in different forms of AML
- Infectious disease specialists who support the needs of patients with suppressed immune systems
- Cardiologists and pulmonologists who address the downstream impacts of cancer treatment on the heart and lungs
These specialists work alongside pharmacists, advanced practice providers, care coordinators, and other teams who collaborate to bring comprehensive care to patients with AML.
“Everyone is involved in treatment in some way,” says El Chaer. “And our updated guidelines lay out the framework that helps these specialties to stay involved, understand new side effects, and be better prepared to participate in care.”
