title: Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age-matched controls: Role of cytomegalovirus.
abstract: 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 late-differentiated 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.
authors.affiliation: University Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.|Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Paediatric Oncology Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Mohamad Shafiq
authors.initials: MS
authors.lastname: Azanan
authors.affiliation: Centre of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Noor Kamila
authors.initials: NK
authors.lastname: Abdullah
authors.affiliation: University Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Chua
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Paediatric Oncology Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Su Han
authors.initials: SH
authors.lastname: Lum
authors.affiliation: University Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sayyidatul Syahirah
authors.initials: SS
authors.lastname: Abdul Ghafar
authors.affiliation: Centre of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.|Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shahrul
authors.initials: S
authors.lastname: Kamaruzzaman
authors.affiliation: Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.affiliation: University Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.|Centre of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.|Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Yin Ling
authors.initials: YL
authors.lastname: Woo
authors.affiliation: University Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.|Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Paediatric Oncology Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Hany
authors.initials: H
authors.lastname: Ariffin
authors.affiliation: Centre of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.|Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Reena
authors.initials: R
authors.lastname: Rajasuriar
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D006801:Humans; D007109:Immunity; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000209:etiology; D007938:Leukemia / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D017741:Survivors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007074:Immunoglobulin G
keywords: Childhood cancer survivors; Cytomegalovirus; Immune activation; Immunologic aging; Systemic inflammation