Estimating the burden of chronic stress through allostatic load in patients with chronic myeloid leukemia

Abstract

Despite advances in tyrosine kinase inhibitor (TKI) therapy, outcomes in chronic myeloid leukemia remain (CML) highly variable, underscoring the need to explore determinants beyond conventional clinical indicators. This study examined the relationship between allostatic load (AL), a biomarker-based index of cumulative chronic stress, social determinants of health (SDH), and treatment outcomes. In a retrospective cohort of 194 patients, AL was calculated using 23 biomarkers spanning cardiovascular, metabolic, hematologic, renal, and hepatic systems. Higher AL was associated with adverse SDH and behavioral factors, including greater extreme poverty (p = 0.02), limited transportation access (p = 0.02), reliance on public health coverage (p = 0.03), and physical inactivity (p = 0.05). Each unit increase in AL reduced the odds of achieving optimal molecular response by 18% (p = 0.02). All 11 disease progressions to advanced CML and all 9 deaths occurred in the high AL group, who also had higher rates of composite adverse events, including loss of molecular response, TKI failure, disease progression, and mortality (p = 0.03). These findings position AL as a promising integrative biomarker to identify high-risk patients facing combined physiological stress burden and social disadvantage, enabling oncology practices to refine risk stratification and implement personalized, multidisciplinary interventions.