Frailty and Fitness in Older Adults With Acute Myeloid Leukemia: From Chronological Age to Multiparametric Assessment

Acute Myeloid Leukemia predominantly affects older adults, who often present with comorbidities, functional impairment, and frailty, limiting eligibility for intensive chemotherapy or allogeneic transplantation. Historically, treatment options were restricted to hypomethylating agents, low-dose cytarabine, hydroxyurea, or supportive care, with poor outcomes. The introduction of hypomethylating agents combined with Venetoclax and the availability of targeted therapies have expanded therapeutic possibilities, challenging the notion that elderly AML is uniformly incurable. In this evolving context, accurate assessment of fitness and frailty is essential to guide treatment decisions. This review summarizes current concepts of frailty in older AML patients, including general geriatric tools and hematology-specific indices. It discusses the role of Comprehensive Geriatric Assessment, frailty phenotypes, and comorbidity scores such as the transplantation-specific comorbidity index and the Charlson index, alongside AML-focused tools like the Ferrara criteria and integrated molecular risk models. Most existing tools were developed in intensively treated cohorts, and their applicability to patients receiving non-intensive regimens remains uncertain. Fitness is increasingly recognized as a dynamic, multidimensional construct incorporating clinical, functional, cognitive, social, and biological factors. A multiparametric approach is proposed, integrating these variables into decision-making models, potentially enhanced by artificial intelligence to optimize treatment selection in older AML patients.