Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease.
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.
Cantoni
Nathan
N
Division of Hematology, University Hospital Basel, Petersgraben 4, Basel, Switzerland. ncantoni@uhbs.ch
Hirsch
Hans H
HH
Khanna
Nina
N
Gerull
Sabine
S
Buser
Andreas
A
Bucher
Christoph
C
Halter
Jörg
J
Heim
Dominik
D
Tichelli
André
A
Gratwohl
Alois
A
Stern
Martin
M
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