Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy: predictors and the relationship with physical activity

Abstract

Fatigue is a common side effect of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients. However, the prevalence of TKI-induced fatigue remains uncertain and little is known about predictors of fatigue and its relationship with physical activity. In this study, 220 CML patients receiving TKI therapy and 110 gender- and age-matched controls completed an online questionnaire to assess fatigue severity and fatigue predictors (Part 1). In addition, physical activity levels were objectively assessed for 7 consecutive days in 138 severely fatigued and non-fatigued CML patients using an activity monitor (Part 2). We demonstrated that the prevalence of severe fatigue was 55.5% in CML patients and 10.9% in controls (P<0.001). We identified five predictors of fatigue in our CML population: age (OR 0.96, 95% CI 0.93-0.99), female gender (OR 1.76, 95% CI 0.92-3.34), Charlson Comorbidity Index (OR 1.91, 95% CI 1.16-3.13), the use of comedication known to cause fatigue (OR 3.43, 95% CI 1.58-7.44), and physical inactivity (OR of moderately active, vigorously active and very vigorously active compared to inactivity 0.43 (95% CI 0.12-1.52), 0.22 (95% CI 0.06-0.74), and 0.08 (95% CI 0.02-0.26), respectively). Objective monitoring of activity patterns confirmed that fatigued CML patients performed less physical activity on both light (P=0.017) and moderate to vigorous intensity (P=0.009). In fact, compared to the non-fatigued patients, fatigued CML patients performed 1 hour less of physical activity per day and took 2000 fewer steps per day. Our findings facilitate the identification of patients at risk of severe fatigue and highlight the importance to set the reduction of fatigue as a treatment goal in CML care. This study was registered at The Netherlands Trial Registry, NTR7308 (Part 1) and NTR7309 (Part 2).

Figure 1.

Flowchart of the study. CML: chronic myeloid leukemia.

Figure 2.

Predicted and observed severe fatigue. The predicted severe fatigue of the multivariable model is plotted against the observed severe fatigue. Each dot represents an individual.

Figure 3.

Activity patterns in severely fatigued and non-fatigued chronic myeloid leukemia patients. Daily time spent sleeping, sitting, performing light intensity physical activity and moderate to vigorous intensity physical activity is shown for both severely fatigued and non-fatigued chronic myeloid leukemia patients. Box and whisker plots represent the median, interquartile range, and 2.5-97.5 percentiles (lower and upper whiskers, respectively). *P<0.05, **P<0.01, ns: not significant.