Many treatment complications that occur late in childhood cancer survivors resemble age-related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of latedifferentiated memory CD57 + CD28 − T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age-matched controls. We found that markers of systemic inflammation-IL-6 and human C-reactive protein and immune activation-CD38 and HLA-DR on T cells, soluble CD (sCD)163 from monocytes and macrophages-were increased in survivors compared to controls. T-cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL-6, human C-reactive protein, sCD163, and CD57 + CD28 − memory T cells.Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age-related comorbidities in this group. Eur. J. Immunol. 2016Immunol. . 46: 1715Immunol. -1726 Introduction Childhood cancer survivors (CCS) have an increased risk of second neoplasms and comorbidities including cardiovascular disease, endocrine dysfunction, renal insufficiency, abnormal lung function, and neurological complications [1,2]. A study in the St. Jude Lifetime cohort also reported that the prevalence of frailty and prefrailty in young CCS (mean age 35 years) were comparable to that of controls who were aged 65 years and older [3]. In addition, CCS have also been associated with an increased risk of multiple infections [4], increased hospital admissions, as well as increased length of hospital stay [5,6]. Collectively, this suggests that the morbidities experienced in young adult CCS are remarkably similar to the spectrum of diseases seen in the elderly.
KeywordsThe increased risk of comorbidities in CCS has largely been attributed to chemotherapy-and radiation-induced damage to specific organs [7,8] and thus referred to as long-term complications of cancer treatment. Postulated reasons for the development of these comorbidities include hormone deficiencies as a result of steroid use and damage to the hypothalamus-pituitary axis following cranial radiotherapy; direct chemotherapy-induced organ damage including anthracycline-induced cardiomyopathy and vincristine-induced neuropathy; and reduced physical activity due to poor self-perception (reviewed in [8]). Most studies assessing these long-term complications in CCS have focused predominantly on the association of these comorbidities with prior exposure to specifi...