Persistent Fatigue in Stem Cell Transplant Survivors: A Biobehavioral Perspective

Topic Significance & Study Purpose/Background/Rationale 

Fatigue is a highly prevalent symptom following hematopoietic stem cell transplantation (HCT) that has been described as intense and lasting for years following treatment.  It is not known why some HCT survivors continue to experience persistent fatigue in the absence of cancer/cancer treatment and how this fatigue compares to occasional tiredness found in the general population. To gain an understanding of persistent fatigue as a biobehavioral phenomenon, this pilot study compared fatigue, physical activity, sleep, emotional distress, cognitive functioning, and biological measures in HCT survivors with persistent fatigue (n=25) to matched healthy controls (HC) with occasional tiredness (N=25). 

Methods, Intervention, & Analysis 

This comparative, descriptive study collected data using a multi-pronged approach: (1) computerized real-time assessments of fatigue over 7 days; (2) objective, real-time assessments of physical activity and sleep over 7 days; (3) patient-reported fatigue assessment using a psychometrically sound questionnaire (Chalder Fatigue Scale) and computerized Adult Short Forms of the PROMIS system (fatigue, sleep disturbances, and emotional distress); (4) computerized objective testing of cognitive functioning to assess sustained attention, memory and executive function; and, (5) biological measures (CBC/Differential, CRP, TNF alpha, and IL-6).  Descriptive statistics were calculated for all measures.  Differences between the HCT survivors and HC were examined using MANOVA. 

Findings & Interpretation 

HCT survivors with persistent fatigue reported increased physical (p < .001), mental (p <.001), and overall fatigue (p < .001) as well as increased anxiety (p < .05) and depression (p< .01) compared to the matched HC group with occasional tiredness.  These differences were clinically significant.  RBC levels were significantly lower in the HCT survivors although levels for both groups were in the normal range.  TNF alpha was significantly higher in the HCT survivors (p < .001).

Discussion & Implications 

These findings provide preliminary evidence for a biobehavioral model of persistent fatigue in HCT survivors.  Persistent fatigue reported by HCT survivors is accompanied by increased anxiety and depression along with decreased RBC levels.  Elevated TNF alpha levels may represent an important biomarker. The role of physical activity, sleep, and cognitive functioning is less clear.  These findings may have important implications for interventions designed to reduce fatigue in HCT survivors.