title: Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients.
abstract: The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.
authors.affiliation: Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. ahmet.elmaagacli@uni-duisburg-essen.de
authors.forename: Ahmet H
authors.initials: AH
authors.lastname: Elmaagacli
authors.forename: Nina K
authors.initials: NK
authors.lastname: Steckel
authors.forename: Michael
authors.initials: M
authors.lastname: Koldehoff
authors.forename: Yael
authors.initials: Y
authors.lastname: Hegerfeldt
authors.forename: Rudolf
authors.initials: R
authors.lastname: Trenschel
authors.forename: Markus
authors.initials: M
authors.lastname: Ditschkowski
authors.forename: Sandra
authors.initials: S
authors.lastname: Christoph
authors.forename: Tanja
authors.initials: T
authors.lastname: Gromke
authors.forename: Lambros
authors.initials: L
authors.lastname: Kordelas
authors.forename: Hellmut D
authors.initials: HD
authors.lastname: Ottinger
authors.forename: Rudolf S
authors.initials: RS
authors.lastname: Ross
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000150:complications; D015536:Down-Regulation; D005260:Female; D020544:Graft vs Leukemia Effect / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous; D014779:Virus Replication / Q000502:physiology*; D055815:Young Adult