Modifiable Factors Associated With Aging Phenotypes Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia

Abstract

Purpose: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for low bone mineral density (BMD) and frail health, outcomes potentially modifiable by altering health behaviors and/or treating endocrine abnormalities. We evaluated associations between lifestyle and hormonal deficits with risk of low BMD and frailty among survivors of ALL.

Patients and methods: Participants included 862 survivors of ALL (median age, 31.3 years [range, 18.4 to 59.7 years]) enrolled in the St Jude Lifetime Cohort study. Bone density was measured using quantitative computed tomography of L1 through L2 vertebrae; low BMD was defined as an age- and sex-standardized z score < -1. The presence of frailty or prefrailty was defined as having at least two of the following: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Hormonal deficiencies were determined according to medical history, medications, and laboratory findings (insulin-like growth factor 1, follicle-stimulating hormone, luteinizing hormone, and testosterone levels). Logistic regression was used to examine associations between lifestyle (smoking, alcohol consumption, and activity levels) and deficiencies in growth hormone (GHD) and/or sex steroids with low BMD and frailty.

Results: Thirty percent of survivors met criteria for low BMD, and 18.6% for frailty/prefrailty. After adjusting for body mass index, low BMD was associated with GHD (odds ratio [OR], 1.59; 95% CI, 1.02 to 2.13) and current smoking (OR, 1.71; 95% CI, 1.02 to 2.85) among men; and GHD (OR, 2.18; 95% CI, 1.26 to 3.78) and moderate alcohol consumption (OR, 2.09; 95% CI, 1.14 to 3.83) among women. After adjusting for current age, the odds of frailty/prefrailty were increased among men with GHD (OR, 2.97; 95% CI, 1.56 to 5.67) and those who smoked (OR, 3.26; 95% CI, 1.65 to 6.43); there were no significant associations among women.

Conclusion: The findings suggest that survivors of ALL should receive counseling regarding lifestyle and undergo screening for hormonal deficits to minimize the risk of low BMD and frailty.

Fig 1.

Study diagram for participation in St Jude Lifetime Cohort Study (SJLIFE). ALL, acute lymphoblastic leukemia; QCT, quantitative computed tomography.

Fig A1.

Reduced-form directed acyclic graph illustrating dependency assumptions for the relations between cranial radiation and low bone mineral density or frailty and hypothesized mediation by hormonal deficiency. Note: The direct effect of cranial radiation on low bone mineral density or frailty was estimated after adjusting for hormonal deficiency (the intermediate). Z1 and Z2 represent covariate vectors on biasing pathways for the exposure-outcome relation and the intermediate-outcome relation, respectively.