Acute myeloid leukemia (AML) is notably more difficult to treat in aging patients due to a complex interplay of biological, clinical, and functional factors that worsen with age. As people grow older, their bodies and disease characteristics change in ways that reduce the effectiveness and tolerability of standard AML treatments, making management more challenging.
One major reason is that older AML patients often have **poorer overall health and more comorbidities**—other chronic illnesses such as heart disease, diabetes, or kidney problems—that complicate treatment. These additional health issues limit the intensity of chemotherapy or other aggressive therapies that can be safely administered. Older adults frequently have reduced organ function and diminished physiological reserves, so they are less able to tolerate the toxic side effects of intensive chemotherapy regimens that younger patients might endure. This leads to a higher risk of treatment-related complications, including infections, organ damage, and early mortality.
Another critical factor is the **biological nature of AML in older adults**. The leukemia cells in elderly patients often carry more adverse genetic mutations and cytogenetic abnormalities, which make the disease more aggressive and less responsive to conventional treatments. These high-risk molecular features are more common with aging and contribute to poorer outcomes. Additionally, older patients tend to have a higher frequency of secondary AML, which arises from prior blood disorders or previous chemotherapy, and this form is typically more resistant to treatment.
Physical function and cognitive status also play a significant role. Many older AML patients experience **declines in mobility, strength, and cognitive abilities**, which can worsen during treatment. These impairments affect their ability to tolerate therapy and recover from side effects. Functional assessments have shown that a large proportion of elderly AML patients have limitations in daily activities and physical performance even before treatment starts. These deficits often worsen during therapy, leading to increased frailty and vulnerability.
Because of these challenges, treatment strategies for older AML patients often differ from those for younger individuals. Intensive chemotherapy, which is standard for younger patients, may not be feasible or safe for many elderly patients. Instead, **lower-intensity therapies**, such as hypomethylating agents combined with targeted drugs like venetoclax, are more commonly used. These regimens aim to balance efficacy with tolerability but still carry risks of prolonged myelosuppression (low blood counts) and infections, which are particularly dangerous in frail older adults.
Moreover, the heterogeneity among older AML patients means that treatment must be highly individualized. Geriatric assessments that evaluate comorbidities, physical and cognitive function, and social support are increasingly used to guide treatment decisions. Patients who score well on these assessments may tolerate more intensive therapies, while those with significant impairments are better suited for less aggressive approaches.
In summary, AML is harder to treat in aging patients because their bodies are less resilient, their leukemia is biologically more aggressive, and they often have multiple health and functional issues that limit treatment options. This combination results in lower survival rates and higher treatment-related risks compared to younger patients. The medical community continues to develop and refine therapies that are better tolerated by older adults, but managing AML in this population remains a significant clinical challenge.