Age-related cytokine effects on cancer-related fatigue and quality of life in acute myeloid leukemia.

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 R 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 >MCID 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.

Conclusion: Cytokines explain a relatively small amount of CRF and QOL scores in patients with AML and effects differ by age group. For cytokine-targeted therapies to improve either outcome, multiple cytokines may need to be substantially altered and therapeutic targets may vary with age.