Persistent Low Level Epstein-Barr Virus DNAemia in Childhood Cancer Survivors

Clinical ascertainment of health outcomes in Asian survivors of childhood cancer: a systematic review

“…A total of 13,442 subjects were represented by the included studies. The majority of the studies were conducted in the following developed countries ( n = 52, 88%): Japan [ 27 , 29 , 30 , 33 , 35 , 38 – 40 , 42 , 43 , 45 , 49 , 54 , 57 , 59 , 61 , 63 , 64 , 67 – 69 , 78 , 80 ] ( n = 24, 41%), South Korea [ 24 , 26 , 31 , 32 , 34 , 37 , 46 , 53 , 55 , 56 , 58 , 60 , 62 ] ( n = 13, 22%), Hong Kong [ 41 , 50 – 52 , 72 – 75 , 76 , 77 , 79 , 81 , 82 ] ( n = 12, 20%), Taiwan [ 47 , 48 ] ( n = 2, 3%), Singapore [ 36 ] ( n = 1, 1.5%). Only seven studies (12%) were conducted in developing countries [ 25 , 28 , 44 , 65 , 66 , 70 , 75 ] (Thailand and Malaysia).…”

“…Only seven studies (12%) were conducted in developing countries [ 25 , 28 , 44 , 65 , 66 , 70 , 75 ] (Thailand and Malaysia). Half of the studies focused on either survivors of childhood leukemia [ 25 , 27 , 28 , 40 , 44 , 46 , 48 , 49 , 58 , 63 , 66 , 70 , 71 , 73 , 74 , 77 – 79 , 81 , 82 ] ( n = 20, 34%) or CNS tumors [ 43 , 45 , 47 , 51 , 52 , 60 , 65 , 67 ] ( n = 8, 13.5%), while the remainder included study samples with heterogeneous cancer diagnoses [ 24 , 26 , 29 – 38 , 41 , 50 , 53 – 57 , 59 , 61 , 62 , 64 , 68 , 69 , 72 , 75 , 76 , 80 ] ( n = 29, 49%) The majority of the included studies had sample sizes of 30–150 subjects ( n = 31, 52.5%), with the exception of six studies with larger cohorts (> 500 subjects) and seven studies with less than 20 subjects. Most studies reported the survivors’ mean duration of follow-up, which ranged from 5 to 15 years after the completion of cancer therapy.…”

“…The vast majority of studies were epidemiological and explicit about the main objectives of reporting the prevalence and risk factors of the following organ-specific toxicities: cardiac [ 72 – 80 ] ( n = 9, 15%); endocrine, fertility, and metabolic [ 53 – 71 ] ( n = 19, 32%); neurologic [ 43 – 45 , 49 , 51 , 52 , 81 , 82 ] and neurocognitive [ 46 – 48 , 50 ] ( n = 12, 20%) and SMN [ 36 – 42 ] ( n = 7, 12%). Clinical endpoints such as dental [ 33 – 35 ], hepatic [ 31 , 32 ], renal [ 30 ], and immunological [ 28 , 29 ] outcomes were less commonly reported (combined n = 8, 14%). Four studies (7%) reported the clinical endpoints of multiple organ systems [ 24 – 27 ].…”

“…Two studies examined the immunological outcomes of survivors [ 28 , 29 ]. Azanan et al reported higher levels of inflammatory cytokines and T cell responses specific to cytomegalovirus among survivors of childhood leukemia relative to non-cancer controls, while Mahmoud et al detected chronically elevated levels of Epstein–Barr virus DNA in 20% of the survivors [ 28 , 29 ].…”

“…Two studies examined the immunological outcomes of survivors [ 28 , 29 ]. Azanan et al reported higher levels of inflammatory cytokines and T cell responses specific to cytomegalovirus among survivors of childhood leukemia relative to non-cancer controls, while Mahmoud et al detected chronically elevated levels of Epstein–Barr virus DNA in 20% of the survivors [ 28 , 29 ]. Additionally, Azanan and colleagues discussed the association between the development of age-related comorbidities and the immune phenotype of aging, as characterized by increased levels of circulating inflammatory cytokines, among survivors [ 28 ].…”