title: Clinical assessment of anti-viral CD8+ T cell immune monitoring using QuantiFERON-CMV® assay to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications.
abstract: The reconstitution of anti-viral cellular immunity following hematopoietic stem cell transplantation (HSCT) is crucial in preventing cytomegalovirus (CMV)-associated complications. Thus immunological monitoring has emerged as an important tool to better target pre-emptive anti-viral therapies. However, traditional laboratory-based assays are too cumbersome and complicated to implement in a clinical setting. Here we conducted a prospective study of a new whole blood assay (referred to as QuantiFERON-CMV®) to determine the clinical utility of measuring CMV-specific CD8+ T-cell responses as a prognostic tool. Forty-one evaluable allogeneic HSCT recipients underwent weekly immunological monitoring from day 21 post-transplant and of these 21 (51.2%) showed CMV reactivation and 29 (70.7%) developed acute graft-versus-host disease (GvHD). Patients with acute GvHD (grade ≥ 2) within 6 weeks of transplant showed delayed reconstitution of CMV-specific T-cell immunity (p = 0.013) and a higher risk of CMV viremia (p = 0.026). The median time to stable CMV-specific immune reconstitution was 59 days and the incidence of CMV reactivation was lower in patients who developed this than those who did not (27% versus 65%; p = 0.031). Furthermore, a failure to reconstitute CMV-specific immunity soon after the onset of CMV viraemia was associated with higher peak viral loads (5685 copies/ml versus 875 copies/ml; p = 0.002). Hence, QuantiFERON-CMV® testing in the week following CMV viremia can be useful in identifying HSCT recipients at risk of complicated reactivation.
authors.affiliation: Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia ; Department of Haematology and Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia ; School of Medicine, University of Queensland, Herston, Queensland, Australia.
authors.forename: Siok-Keen
authors.initials: SK
authors.lastname: Tey
authors.forename: Glen A
authors.initials: GA
authors.lastname: Kennedy
authors.forename: Deborah
authors.initials: D
authors.lastname: Cromer
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Susan
authors.initials: S
authors.lastname: Walker
authors.forename: Linda I
authors.initials: LI
authors.lastname: Jones
authors.forename: Tania
authors.initials: T
authors.lastname: Crough
authors.forename: Simon T
authors.initials: ST
authors.lastname: Durrant
authors.forename: James A
authors.initials: JA
authors.lastname: Morton
authors.forename: Jason P
authors.initials: JP
authors.lastname: Butler
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Misra
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001681:Biological Assay; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003587:Cytomegalovirus / Q000472:pathogenicity / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D014184:Transplantation, Homologous; D019562:Viral Load; D014775:Virus Activation