Novel Data on Rare Gene Mutation in Children With AML Indicate Need for High-Risk Status

The clinical understanding of acute myeloid leukemia (AML) has evolved exponentially in the last few decades, according to Adam Lamble, MD, Attending Physician, Assistant Professor of Pediatrics, Cancer & Blood Disorders Center, High-Risk Leukemia Program, Leukemia & Lymphoma Program, Seattle Children's Hospital.

"As we learn more, it's getting even more and more complicated, but I think that's also allowing us to really fine tune our treatment approaches and make them more patient-specific," he said in an interview.

Lamble led the largest investigation of TP53 mutations in pediatric patients with acute myeloid leukemia and presented the data at the American Society of Hematology (ASH) Annual Meeting and Exposition. The team's findings confirmed that this gene mutation is incredibly rare in children with the condition (1.5%), which is divergent from the prevalence seen in adults with AML.

"Until now, we didn't really know what to do with a patient with a TP53 mutation," he said. "But when you see that their outcomes are inferior to other patients with high risk disease, I think that that's really informative that these patients probably deserve to be considered high risk."

Despite scarcity of the TP53 mutation in pediatric AML, Lamble noted that pediatric oncologists are likely to treat a child with this genetic mutation at least once in the span of their career.

"We did see an association with something called complex cytogenetics—when a patient has 3 or more structural alterations in their karyotype," he explained. "This is very well described in adults, and so it wasn't too surprising to us."

The results demonstrated that these patients are just as likely to achieve remission, however, they're much more likely to relapse.

"Of the patients that we had data available, 77% of them ultimately relapsed, which led to an event-free survival of only 13%, and 13% event-free survival is definitely inferior when you compare it to patients without TP53 mutation," he said. "But, I think what was really informative to us is, this is even inferior to those patients that we have temporarily defined as high risk."

Learn more about Dr. Adam Lamble's study in HCPLive's interview.