Relationship between Fatigue and Cytokine Levels in Patients Age 50+ with Acute Myeloid Leukemia (AML).
Authors: Panju Abbas H. , Kelvin David , Minden Mark D. , Alibhai Shabbir M.H. 
Published: October 2019

Abstract
Several studies have found fatigue to be the most common, persistent, and disabling symptom affecting patients with AML. Effective measures to prevent or treat fatigue have yet to be found. Cytokines, biological markers of inflammation, may represent one potential intervention target, but data on the fatigue-cytokine relationship in AML are limited to one small published study. We examined this relationship in patients age 50 or older with AML, fluent in English, within one year of AML diagnosis, and free of any other active malignancy. Fatigue was measured using the Functional Assessment of Cancer Therapy (FACT) Fatigue subscale and a single-item global fatigue scale. Quality of life (QOL) and depression were assessed using the European Organization for the Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the Hospital Anxiety and Depression Scale (HADS), respectively. Blood was simultaneously drawn for quantitative measurement of a panel of cytokines. Patients were reassessed 4–6 weeks later, and the same set of questionnaires were administered and a second blood sample drawn. Pearson’s correlation was used to examine relationships between individual cytokines and fatigue scores. Variables were transformed as necessary. For patients with data at two time points, changes in fatigue scores were correlated with changes in cytokines.
At the time of submission, 31 patients (20 males; 11 females) have been enrolled (mean age 67 y; range 52–84). 32% had not started active chemotherapy or were receiving best supportive care, while the remainder were undergoing active chemotherapy. At the first time point (t1), no moderate or strong correlations were observed with any of the cytokines and at least one fatigue score. Weak correlations (0.30<r<0.50) were seen with interleukin(IL)-5, IL-6, IL-8, and IL-10 with at least one fatigue measure. No correlations (r<0.30) were observed with any of the other cytokines tested (interferon (IFN)-γ, IL-1β, IL-2, IL-4, IL-12, interferon-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, monokine induced by gamma-IFN (MiG), and tumour necrosis factor (TNF)-α). Among patients with follow-up data, a moderate correlation (0.50<r<0.70) was noted between changes in IL-6 level and fatigue scores. Changes in concentrations of IFN-γ, IL-1β, IL-2, IL-5, IL-8, IL-10, IP-10, and MiG showed weak correlation with changes in at least one fatigue measure. A moderate correlation was observed between age and IL-1β but no age relationship was noted for any of the other cytokines. There was no correlation between fatigue and age but there were moderate to strong correlations between fatigue and depression.
Based on these data, the most consistent relationships between concentrations of cytokines and fatigue were noted with IL-5, IL-6, and IL-8, and these show the most promise for future studies. Our study bore two notable limitations: the first was the small sample size, and the second was the recruitment of patients at differing time points during their treatment course. Further patient enrolment and data collection are underway to validate our findings and clarify the significance of these preliminary results.