Pilot study: Assessing allostatic load score and outcomes in Acute Myeloid Leukemia patients in North Carolina

Abstract Background: Allostatic load (AL) represents the cumulative systemic stress burden on an individual's body, involving neuroendocrine and immune mediators such as cortisol, catecholamines, and inflammatory cytokines. Increased AL contributes to dysfunction in metabolic, cardiovascular, and immune systems, and has been associated with increased cancer incidence, aggressive tumor phenotypes, and worse clinical outcomes, particularly in solid tumors. However, associations of AL in hematologic malignancies, including acute myeloid leukemia (AML), remain unclear. Objective: To examine AL scores in a small cohort of AML patients in North Carolina, focusing on identifying opportunities for understanding the relationship between AL and outcomes in AML. Methods: We retrospectively analyzed data from 40 randomly selected AML patients diagnosed between 2018–2023. Data collected included: patient demographics, comorbidities, molecular and cytogenetic profiles, and available biomarker variables (body mass index, lactate dehydrogenase, albumin, creatinine, estimated glomerular filtration rate, resting heart rate, baseline systolic/diastolic blood pressure, and fasting glucose). The AL score was constructed using a commonly applied approach of summing indicator scores derived from each variable. Linear regression was used to assess the relationship between the individual indicators and probability of mortality at any time point after diagnosis. Results: The cohort included 20 males (median age 64 years), 20 females (median age, 58.5 years), 29 Non-Hispanic White patients, and 20 patients from other ethnic backgrounds. Key AL biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6), and cholesterol levels were largely missing in this retrospective data set.The median AL score was 6 (range: 3–10), and a score ≥ 6 was defined as high. Patients with high AL scores had a significantly increased probability of mortality at any time point after diagnosis (p = 0.01). AL scores did not differ significantly by sex or ethnicity, but adverse molecular and cytogenetic profiles (p = 0.002) and smoking status (p = 0.049) were also associated with increased mortality. Conclusion: The preliminary findings from this pilot study suggest a relationship between high AL score and mortality in AML patients. Additional investigations with an expanded cohort are warranted to further assess the relationship between high AL scores, outcomes, and survival. While the absence of key biomarkers like CRP, IL-6, and cholesterol limits comprehensive assessment of AL scoring in this cohort, future research will focus on prospectively incorporating comprehensive biomarker data to better define the prognostic role of AL in AML. Integrating AL assessment into clinical care may enhance risk stratification, guide treatment decisions, and support a more holistic approach to AML management.