High Prevalence of Chronic Fatigue in Adult Long-Term Survivors of Acute Lymphoblastic Leukemia and Lymphoma During Childhood and Adolescence

Purpose: Chronic fatigue (CF) is a frequent late effect of cancer, but has been poorly studied in adult survivors of childhood cancer. This cross-sectional study compares the prevalence of CF among adult survivors (childhood leukemia/lymphoma survivors; CLSs) of childhood acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) to controls, and explored CF's association with disease characteristics, treatment, mental and somatic late effects, and selected markers of low-grade inflammation. Methods: A total of 143 male and 147 female CLSs participated in this study, which comprised a questionnaire, clinical examination, and blood samples. The control group consisted of 1405 individuals from the Norwegian general population. The Chalder Fatigue Questionnaire assessed CF. Results: Median age at survey and observation time was 29.6 years and 21.1 years, respectively. The prevalence of CF was 27% among CLSs (ALL 22%, NHL 30%, HL 34%) versus 8% among controls. Compared to controls and adjusting for age and sex, the probability of having CF among CLS was elevated (odds ratio [OR] = 4.5; 95% confidence interval [CI]: 3.1-6.4). In lymphoma survivors, presence of B-symptoms at diagnosis predicted CF in univariate analysis. Elevated levels of anxiety and depression predicted CF in multivariate analysis. Disease characteristics and treatment or somatic late effects were not associated with CF. Leukocyte, neutrophil, and trombocyte counts were elevated among subjects with CF. Conclusion: At a median of 20 years after diagnosis, the prevalence of CF in CLSs is more than three times that of the general population. A persistent low-grade inflammatory response may be involved in the pathogenesis of CF.