title: Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease.
abstract: Cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) are important complications after allogeneic hematopoietic stem cell transplantation (HSCT) with a clear link. Multiple studies show that GVHD and its treatment put patients at risk for CMV replication. Data on CMV replication as a cause of GVHD, in contrast, are controversial. We analyzed the reciprocal association of CMV replication with acute GVHD (aGVHD) in 515 patients treated with allogeneic HSCT between 1993 and 2008. Cumulative incidences at day 100 were 17% for CMV replication, 68% for aGVHD grade I-IV, and 48% for GVHD grade II-IV. Multivariate time-dependent analyses revealed that the presence of GVHD increased the risk of CMV replication in a dose-dependent manner: hazard ratio (HR) for CMV replication for patients with aGVHD grade I was 1.35 (95% confidence interval [CI] 0.82-2.21); HR for patients with aGVHD grade II-IV was 1.61 (95% CI 1.11-2.36, P-value for trend = .01). During phases of CMV replication, patients were at increased risk of developing aGVHD (HR 2.18, 95% CI 1.30-3.65, P < .01). These data confirm that GVHD and its therapy can induce CMV replication. They further demonstrate the reciprocal novel finding that patients are at significantly increased risk of developing aGVHD during CMV replication.
authors.affiliation: Division of Hematology, University Hospital Basel, Petersgraben 4, Basel, Switzerland. ncantoni@uhbs.ch
authors.forename: Nathan
authors.initials: N
authors.lastname: Cantoni
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Nina
authors.initials: N
authors.lastname: Khanna
authors.forename: Sabine
authors.initials: S
authors.lastname: Gerull
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.forename: Christoph
authors.initials: C
authors.lastname: Bucher
authors.forename: Jörg
authors.initials: J
authors.lastname: Halter
authors.forename: Dominik
authors.initials: D
authors.lastname: Heim
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014779:Virus Replication; D055815:Young Adult