An international investigation carried out by the Alliance for Clinical Trials in Oncology and the Acute Myeloid Leukemia Cooperative Group indicates that categorizing acute myeloid leukemia (AML) patients by age may no longer be appropriate.
AML is a rapidly progressing blood and bone‑marrow cancer that predominantly affects older adults. Past guidelines have used age as a key determinant of treatment intensity, eligibility for clinical studies, and the use of targeted drugs. However, this new evidence shows that age alone does not reliably indicate the biology of the disease or its outlook.
"Our results support a shift toward a biology‑driven strategy for AML treatment and for designing studies. Age should never be the sole barrier to life‑saving therapies," explained lead author Ann‑Kathrin Eisfeld, MD, associate professor of Internal Medicine and director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University.
"By prioritizing molecular and genetic profiles over chronological age, clinicians can more accurately personalize therapy, improving outcomes and widening access to novel treatments," Eisfeld added.
The study, published in Leukemia, reviewed data from 2,823 adult AML patients who received frontline therapy in large cooperative group trials in the United States (CALGB/Alliance) and Germany (AMLCG). It identified subtle, age‑related differences in genetic mutations and survival that question current clinical norms. This is the first extensive, cross‑continental study to examine mutational patterns and outcomes across all age groups in AML.
LeukemiaThe analysis encompassed patients treated with standard cytarabine‑based chemotherapy from 1986 to 2017. Targeted sequencing identified genomic features, and outcomes were evaluated using the 2022 European LeukemiaNet (ELN) genetic‑risk system.
The research found no distinct age cut‑off that could separate patients into separate biological or prognostic categories. Instead, genetic mutations and survival outcomes varied continuously with age, undermining the common practice of using arbitrary thresholds such as 60 or 65 years for decision making.
Survival rates steadily decreased with age even in cases of favorable genetic risk. For example, 18‑ to 24‑year‑olds with favorable‑risk AML had a five‑year overall survival of 73%, whereas patients 75 and older had only 21%. This pattern persisted across all risk categories, showing that age negatively affects prognosis irrespective of genetic classification.
"Our findings arrive at a pivotal moment in oncology as precision medicine reshapes cancer care," said Dr. Eisfeld. "Many targeted agents remain available only to patients above a certain age, dictated by inclusion criteria of major trials, even though patients outside that range could also benefit from less toxic options."