title: Donor serostatus has an impact on cytomegalovirus-specific immunity, cytomegaloviral disease incidence, and survival in seropositive hematopoietic cell transplant recipients.
abstract: More cytomegalovirus (CMV)-specific T cells are transferred with grafts from CMV seropositive than seronegative donors. We hypothesized that seropositive recipients of grafts from seropositive donors (D+R+) have higher counts of CMV-specific T cells than seropositive recipients of grafts from seronegative donors (D-R+), and that this is clinically relevant in the setting of in vivo T cell depletion using rabbit-antihuman thymocyte globulin (ATG). We reviewed charts of 298 ATG-conditioned, seropositive recipients for CMV reactivation (pp65 antigenemia or CMV DNAemia above institutional threshold for preemptive therapy), recurrent CMV reactivation, CMV disease, and death. In 77 of these patients, we enumerated CMV-specific T cells. Median follow-up was 564 days. CMV-specific CD4+ and, to a lesser degree, CD8+ T cell counts were higher in D+R+ than D-R+ patients. D+R+ patients had lower cumulative incidence of CMV reactivation (21% versus 48%, P < .001), recurrent reactivation (4% versus 15%, P = .003), CMV disease (3% versus 13%, P = .005) and mortality (42% versus 56%, P = .006). We conclude that in the setting of in vivo T cell depletion using ATG, seropositive donors should be used for seropositive recipients. For scenarios where only seronegative donors are available, strategies to improve CMV-specific immunity (e.g., donor vaccination) should be explored.
authors.affiliation: Department of Medicine, University of Calgary, 3330 University Drive NW, Calgary, Alberta, Canada.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ugarte-Torres
authors.forename: Mette
authors.initials: M
authors.lastname: Hoegh-Petersen
authors.forename: Yiping
authors.initials: Y
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Williamson
authors.forename: Diana
authors.initials: D
authors.lastname: Quinlan
authors.forename: Sarah
authors.initials: S
authors.lastname: Sy
authors.forename: Lina
authors.initials: L
authors.lastname: Roa
authors.forename: Faisal
authors.initials: F
authors.lastname: Khan
authors.forename: Kevin
authors.initials: K
authors.lastname: Fonseca
authors.forename: James A
authors.initials: JA
authors.lastname: Russell
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014611:Vaccination / Q000379:methods