PURPOSE:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) relies heavily on donations from unrelated donors (UDs). This study aimed to examine longitudinal changes in symptoms among UDs and identify associated predictors from the initiation of mobilization through the first post-donation year. METHODS:UDs registered with the China Marrow Donor Program who were scheduled to donate hematopoietic stem cells at a public hospital in China were enrolled. A total of 139 UDs completed the Allo-HSCT Donor Symptom Assessment Scale at nine time points. Repeated-measures analysis of variance and linear mixed-effects models were used to analyze changes in symptoms over time and associated predictors. RESULTS:The total symptom score and all seven symptom dimensions changed significantly over time. Overall symptom burden followed an inverted U-shaped temporal pattern (F = 151.934, P < 0.001), peaking on day 4 of mobilization and declining to near-baseline levels by two weeks post-donation. The pain-related symptom dimension showed the greatest fluctuation (F = 210.642, P < 0.001), followed by the morbid sensation and body temperature symptom dimensions (F = 66.929, P < 0.001; F = 17.671, P < 0.001, respectively). The peripheral sensory symptom dimension showed a distinct pattern, peaking on the day of apheresis. Individual symptoms within dimensions demonstrated considerable heterogeneity. Higher symptom burden was associated with older age and higher BMI. Protective factors included being male, engaging in regular physical activity, and having blood type A (vs. type O). CONCLUSION:This study provides the first detailed longitudinal characterization of symptom changes in UDs, revealing distinct phase-specific patterns. Regular physical activity may represent a potentially modifiable protective factor for reducing symptom burden.