Immunity in young adult survivors of childhood leukemia is more similar to elderly rather than age-matched controls: Role of cytomegalovirus (CMV)

Many treatment complications which occur late in childhood cancer survivors resemble age-related co-morbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation and accumulation of late-differentiated memory CD57⁺CD28⁻ T cells has been associated with co-morbidities 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 (hCRP) and immune activation – CD38 and HLA-DR on T cells, sCD163 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, hCRP, 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 co-morbidities in this group.

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