title: The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality.
abstract: Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007 to 2014. We used quantitative PCR to test for cytomegalovirus, BK polyomavirus, human herpesvirus 6B, HHV-6A, adenovirus, and Epstein-Barr virus between days 0 and 100 post-HCT. We evaluated risk factors for detection of multiple viruses and association of viruses with mortality through day 365 post-HCT with Cox models. Among 404 allogeneic HCT recipients, including 125 cord blood, 125 HLA-mismatched, and 154 HLA-matched HCTs, detection of multiple viruses was common through day 100: 90% had ≥1, 62% had ≥2, 28% had ≥3, and 5% had 4 or 5 viruses. Risk factors for detection of multiple viruses included cord blood or HLA-mismatched HCT, myeloablative conditioning, and acute graft-versus-host disease (Pvalues < .01). Absolute lymphocyte count of <200 cells/mm3was associated with greater virus exposure on the basis of the maximum cumulative viral load area under the curve (AUC) (P= .054). The maximum cumulative viral load AUC was the best predictor of early (days 0-100) and late (days 101-365) overall mortality (adjusted hazard ratio [aHR] = 1.36, 95% confidence interval [CI] [1.25, 1.49], and aHR = 1.04, 95% CI [1.0, 1.08], respectively) after accounting for immune reconstitution and graft-versus-host disease. In conclusion, detection of multiple dsDNA viruses was frequent after allogeneic HCT and had a dose-dependent association with increased mortality. These data suggest opportunities to improve outcomes with better antiviral strategies.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.|Vaccine and Infectious Disease Division and.
authors.forename: Joshua A
authors.identifier: 0000-0002-7665-7100
authors.initials: JA
authors.lastname: Hill
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Mayer
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Hu
authors.initials: H
authors.lastname: Xie
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA.
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Vaccine and Infectious Disease Division and.
authors.forename: Terry
authors.initials: T
authors.lastname: Stevens-Ayers
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Filippo
authors.initials: F
authors.lastname: Milano
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.affiliation: Chimerix Inc., Durham, NC; and.
authors.forename: Garrett
authors.initials: G
authors.lastname: Nichols
authors.affiliation: Seattle Children's Research Institute, Seattle, WA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Zerr
authors.affiliation: Vaccine and Infectious Disease Division and.|Department of Laboratory Medicine, University of Washington, Seattle, WA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.|Vaccine and Infectious Disease Division and.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Schiffer
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.|Vaccine and Infectious Disease Division and.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000302:isolation & purification; D000257:Adenoviridae Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality* / Q000821:virology; D000328:Adult; D019540:Area Under Curve; D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification; D002648:Child; D036101:Cord Blood Stem Cell Transplantation / Q000401:mortality; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006566:Herpesviridae Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality* / Q000821:virology; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D019562:Viral Load
chemical_list: D004279:DNA, Viral