Findings from a study published by Eisfeld et al in the journal Leukemia could refine an important set of prognostic and treatment recommendations for younger adult patients with acute myeloid leukemia (AML).
The retrospective study evaluated the molecular characteristics and outcomes of 863 patients with AML who were treated according to 2017 European LeukemiaNet (ELN) recommendations. The patients were all younger than age 60, with a median age of 45 years. ELN recommendations are internationally used for diagnosing and managing people with AML and other leukemias. Only 35% to 40% of patients with AML younger than 60 achieve long-term survival, the researchers noted.
Methods
The research team detected 2,354 mutations, for an average of 3 per patient. The researchers also determined the frequency of mutations additional to those used to define current ELN risk groups, and mutations in several “functional group” categories: RAS pathway mutations; kinase- and methylation-related mutations; and mutations in genes encoding for spliceosomes, transcription factors, and tumor suppressors.
They compared the frequencies of the mutations within each ELN risk group—favorable, intermediate, and high—to learn which were associated with better or worse outcomes and might therefore help refine the 2017 ELN classification.
Findings and Reclassifications
The study found that 9% of favorable-risk and 53% of intermediate-risk patients should be reclassified as adverse-risk; and 4% of favorable-risk and 9% of adverse-risk patients should be reclassified as intermediate-risk.
Other key findings include:
- BCOR- or SETBP1-mutated favorable-risk patients with non–core-binding factor AML and IDH-mutated adverse-risk patients had intermediate-risk outcomes.
- Outcomes of NPM1/WT1 comutated patients and those of ZRSR2-mutated patients resembled outcomes of adverse-risk patients.
- FLT3-ITD–high allelic ratio conferred adverse risk, rather than intermediate risk, regardless of NPM1 mutation status.
- DNMT3A mutations signaled very poor survival.
“If verified, our findings may refine the ELN risk stratification of younger [patients with] acute myeloid leukemia, which could improve patients' treatment choices and outcomes,” said first author Ann-Kathrin Eisfeld, MD, in a statement.
Disclosure: For full disclosures of the study authors, visit nature.com.
