Abstract
Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.
Highlights
Persistent fatigue is a subjective experience of tiredness, exhaustion and lack of energy that has a negative impact on daily life and functioning
The defects in energy metabolism could be responsible for post exertional malaise, a key clinical finding associated with fatigue in chronic fatigue syndrome/myalgic encephalopathy (CFS/ME)
No similar differences in amino acid concentrations were found when we compared lymphoma survivors after HDT-ASCT that suffer from cancer-related fatigue (CF) to survivors without CF
Summary
Persistent fatigue is a subjective experience of tiredness, exhaustion and lack of energy that has a negative impact on daily life and functioning It is a common symptom in a wide variety of disorders, for instance, in patients with inflammatory or infectious diseases, depression disorder and cancer [1,2,3]. CF has been described in 25–35% of long-term survivors of breast cancer, lymphoma or testicular cancer in Norway, compared to 11% in a national representative population [7,8,9,10] These patients are cured of their malignancies but may suffer from other late effects where fatigue may be an associated symptom. Some studies point to an ongoing low grade inflammatory process in patients with CF after breast cancer or lymphoma [15,16,17]
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