Abstract
Objective: Circadian rhythm disruption has been implicated in the progression of hematologic malignancies, yet its physiological impact remains poorly understood. This study aimed to evaluate the prevalence of circadian rhythm disruption and investigate its association with hematopoietic and systemic physiological functions in patients with hematologic malignancies.
Design: Cross-sectional study.
Setting: Tertiary hospitals in Hubei Province, China; data collected between January 2025 and July 2025.
Participants: 212 patients diagnosed with hematologic malignancies and receiving treatment at three tertiary hospitals.
Main outcome measures: Circadian rhythm disruption was assessed using the Pittsburgh Sleep Quality Index (PSQI), focusing on the sleep disturbance and daytime dysfunction dimensions. Higher scores indicated greater disruption. Concurrent hematologic and biochemical parameters were collected, and key biomarkers were classified into four pathophysiological dimensions: hematopoietic function, inflammatory response, metabolic stress, and coagulation function. Principal component analysis (PCA) was applied within each dimension to derive composite indices by weighting the first two components based on their explained variance and standardizing the results. Restricted cubic spline (RCS) models were applied to examine non-linear associations between circadian disruption and hematopoietic function, adjusting for treatment and disease subtype. Interaction effects with age, sex, and diagnosis were explored. The primary outcome was hematopoietic function; secondary outcomes included indices of inflammation, metabolism, and coagulation.
Results: Among 212 patients (59.6% male; median age 60), 63.4% had poor sleep quality and 84.6% reported daytime dysfunction. Baseline demographics showed no significant differences. PCA-derived indices captured substantial domain variance (97.85%, 59.53%, 78.66%, 71.52% for hematopoiesis, inflammation, metabolism, and coagulation, respectively). RCS models showed no multicollinearity and normally distributed residuals. Daytime dysfunction exhibited a progressively decreasing non-linear association with hematopoietic function, with a pronounced decline observed above a score of 1 (β = -0.38, 95% CI:-0.49 to -0.27, p = 9.65e-12). Nighttime rhythm disruption showed a steep initial negative effect that plateaued beyond a score of 2 (β = -0.24, 95% CI:-0.36 to -0.13, p = 3.62e-05), suggesting early-effect saturation. No significant interactions were found with age or sex, but the adverse effect of circadian disruption on hematopoietic function was more pronounced in patients with myelodysplastic syndromes. No significant associations were observed between circadian disruption and inflammation or metabolism; however, a negative association with coagulation function was noted at lower levels of sleep disturbance (<2 points).
Conclusions: Circadian rhythm disruption was non-linearly associated with impaired hematopoietic function in patients with hematologic malignancies, particularly in cases of moderate to severe daytime dysfunction and early-stage sleep disturbance. These associations were stronger in patients with myelodysplastic syndromes, suggesting greater vulnerability to circadian disruption in this subgroup.
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