Biobehavioral mechanisms underlying symptoms in cancer patients with chronic graft-versus-host disease

Abstract

Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplant (HCT) and is associated with morbidity and high symptom burden. This study evaluated two biobehavioral mechanisms, inflammation and circadian rest-activity rhythms, that may underly commonly reported psychological and physical symptoms in cGVHD patients. Adults with cGVHD (N=57) wore a wrist actigraph for 7 days, provided a blood sample, and completed patient-reported outcome (PRO) measures. 24-hour rest-activity indices were derived from actigraphy. Cytokines and chemokines relevant to cGVHD were measured in peripheral blood plasma using multi-analyte immunoassays. Multiple regression evaluated the extent to which rest-activity indices and inflammatory biomarkers predicted PROs. Higher levels of circulating IL-8 and MIP-1α were associated with worse depression (β = 0.35, p = 0.01; β = 0.33, p = 0.02) and sexual function (β = -0.41, p = 0.01; β = -0.32, p = 0.03). MIP-1α was associated with more severe insomnia (β = 0.36, p = 0.01). Higher circulating MIF was associated with more severe anxiety (β = 0.28, p = 0.048) and fatigue (β = 0.35, p = 0.02). Il-6, TNFα, and MCP-1 showed few associations with PROs. There were few associations between actigraphy indices and PROs; however, participants with a later daily activity peak (acrophase) reported poorer sexual function (β = -0.31, p = 0.04). Models covarying for age, cGVHD severity, and time since HCT yielded a similar pattern of results. Results suggest that pro-inflammatory cytokines and chemokines associated with cGVHD may contribute to PROs, identifying a biobehavioral mechanism that may be a useful target for future interventions.