title: Expansion of recipient-derived antiviral T cells may influence donor chimerism after allogeneic stem cell transplantation.
abstract: Donor chimerism (DC) analysis is an important marker in the hematopoietic stem cell transplant follow-up. Here, we present evidence for a possible relationship of infectious complications and declines in DC. We analyzed the DC in patients experiencing cytomegalovirus (CMV) reactivation. In addition, in some patients chimerism analyses of T-cell subsets were performed. CMV-specific cytotoxic T-lymphocytes (CMV-CTL) were monitored using human leukocyte antigen-restricted multimer staining. Interestingly, CMV reactivation was accompanied by changes in DC in 11 of 67 patients transplanted. For example, DC declined in a cord blood recipient, in both total leukocytes and CD4 and CD8 T-cell subsets upon CMV reactivation. The latter was controlled after only 5 days through expanding CMV-CTL of 96% recipient origin, according to chimerism analysis of CMV-CTL (enriched beyond 50%). In another patient, transplanted after reduced-intensity conditioning from a DQB1 mismatched, CMV seronegative donor, incipient CMV reactivation was completely aborted by CMV-CTL of recipient origin. However, at the same time, mixed chimerism dropped from 51% to 0% donor type, resulting in late graft rejection. Our data indicate that chimerism analyses in subset populations lead to a better understanding of declining total leukocyte chimerism. Furthermore, recipient-derived CMV-CTL may be able to control CMV reactivation after reduced-intensity conditioning. We speculate that autologous CMV-CTL may be instrumental to overcome recurrent CMV reactivations, especially in patients transplanted from CMV-seronegative donors. In addition, the expansion of recipient-derived CMV-CTL may contribute to both, graft failure or to conversion to full DC.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Borchers
authors.forename: E M
authors.initials: EM
authors.lastname: Weissinger
authors.forename: B
authors.initials: B
authors.lastname: Pabst
authors.forename: T
authors.initials: T
authors.lastname: Ganzenmueller
authors.forename: E
authors.initials: E
authors.lastname: Dammann
authors.forename: S
authors.initials: S
authors.lastname: Luther
authors.forename: H
authors.initials: H
authors.lastname: Diedrich
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.forename: M
authors.initials: M
authors.lastname: Stadler
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D046528:Chimerism; D003586:Cytomegalovirus Infections / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019172:Transplantation Conditioning; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
keywords: CMV; cytomegalovirus; cytotoxic T-lymphocytes; donor chimerism; stem cell transplantation