A new study involving patients with chronic graft-versus-host disease (cGVHD) found fatigue was associated with multiple patient-reported factors, but not with any examined cGVHD-related biomarkers or survival outcomes. Results of the study were reported in the journal Bone Marrow Transplantation.

The study investigators explained that fatigue in patients with cGVHD is commonly linked to a decreased health-related quality of life and that patients with cGVHD show higher levels of fatigue than is seen in the general population. However, factors associated with fatigue in patients with cGVHD have been unclear.

This National Institutes of Health (NIH) study on cGVHD natural history (ClinicalTrials.gov Identifier: NCT00092235) included patients who had moderate-to-severe cGVHD based on NIH criteria. Patient-reported outcome measures were used to assess patient symptoms, dietary intake, and several other features. Fatigue in patients in this study was defined by a short form 36 health survey (SF-36) vitality score less than 40. Several clinical and laboratory characteristics, including levels of cytokine biomarkers, were compared between a total of 109 patients considered fatigued and 72 patients considered nonfatigued, to identify factors associated with fatigue.

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Several factors were found by univariate analysis to be associated with fatigue in this study population. Some of these included self-reported SF-36 physical and mental health scores, NIH joint-fascia score, 2-minute walk test distance, human activity profile scores, Karnofsky performance status, and several Lee symptom scores.

Multivariable analysis identified the following predictors of fatigue: patient-generated subjective assessment tool (PG-SGA) activities and function score (odds ratio [OR], 2.05; 95% CI, 1.35-3.10; P =.0007), difficulty sleeping (OR, 1.82; 95% CI, 1.30-2.54; P =.0004), NIH joint-fascia score (OR, 1.49; 95% CI, 1.04-2.15; P =.03), and depression (OR, 1.48; 95% CI, 1.04-2.11; P =.03).

The researchers did not identify any cGVHD biomarkers linked to fatigue, and overall survival rates did not appear to differ between fatigued and nonfatigued groups. Depression and insomnia were reportedly more common among fatigued than nonfatigued patients, but both groups used antidepressants and sleep aids at similar rates.

The researchers concluded that fatigue with cGVHD may be related to factors beyond disease activity. “Clinical characteristics such as NIH joint score, PG-SGA activity and function scores, and Lee sleep and depression scores are significantly associated with presence of fatigue in cGVHD indicating points for targeted therapeutic interventions,” the researchers concluded.


Goklemez S, Saligan LN, Pirsl F, et al. Clinical characterization and cytokine profile of fatigue in hematologic malignancy patients with chronic graft-versus-host disease. Bone Marrow Transplant. Published online August 25, 2021. doi:10.1038/s41409-021-01419-2