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    Journal of Geriatric Oncology xxx (2019) xxx
    Contents lists available at ScienceDirect
    Journal of Geriatric Oncology
    Age-related cytokine effects on cancer-related fatigue and quality of life in acute myeloid leukemia
    Shabbir M.H. Alibhai a,b,c, , Henriette Breunis a, John Matelski a,d, Narhari Timilshina a, Arjun Kundra e, Chieh-Hsin Lee f, Madeline Li e
    a Department of Medicine, University Health Network, Toronto, Canada
    b Department of Medicine, University of Toronto, Toronto, Canada
    c Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Canada
    d Biostatistics Research Unit, University Health Network, Toronto, Canada
    e Department of Psychiatry, University Health Network, Toronto, Canada
    f Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada
    Article history:
    Received in revised form 20 February 2019 Accepted 9 April 2019 Available online xxxx
    Acute myeloid leukemia
    Cancer-related fatigue
    Quality of life
    Tumor necrosis factor
    Objectives: We determined whether cytokines are a potential target to improve cancer-related fatigue (CRF) and quality of life (QOL) in acute myeloid leukemia (AML).
    Methods: 219 patients age 18+ undergoing intensive chemotherapy for AML were assessed at up to 4 time points (pre-treatment, 1 month, 6 months, 12 months). CRF and QOL were assessed with validated patient-reported outcome measures with minimum clinically important differences (MCID) of 4 and 10 points, respectively. A panel of 31 plasma cytokines was measured. CRF and QOL were regressed against scaled cytokine values, adjusting for age, gender, time, remission status, and hemoglobin in linear models.
    Results: 498 cytokine samples were available. For CRF, the model R2 was 25.3%, with cytokines explaining 6.9% of the variance. For QOL, corresponding values were 27.9% and 7.4%, respectively. A shift from the 30th to 70th centile distribution of all cytokines was associated with an improvement in CRF by 5.2 points and a 10.2-point improvement in QOL. A shift from 5th to 95th centile in TNF-α but no other single cytokine was associated with a change of NMCID in CRF, but there was no similar association with QOL. Cytokines had greater explanatory power for CRF in older versus younger adults and the most influential cytokines differed by age, particularly TNF-α.