title: Association of disparities in known minor histocompatibility antigens with relapse-free survival and graft-versus-host disease after allogeneic stem cell transplantation.
abstract: Allogeneic stem cell transplantation (allo-SCT) can induce remission in patients with hematologic malignancies due to graft-versus-tumor (GVT) responses. This immune-mediated antitumor effect is often accompanied by detrimental graft-versus-host disease (GVHD), however. Both GVT and GVHD are mediated by minor histocompatibility antigen (MiHA)-specific T cells recognizing peptide products from polymorphic genes that differ between recipient and donor. In this study, we evaluated whether mismatches in a panel of 17 MiHAs are associated with clinical outcome after partially T cell-depleted allo-SCT. Comprehensive statistical analysis revealed that DNA mismatches for one or more autosomal-encoded MiHAs was associated with increased relapse-free survival in recipients of sibling transplants (P = .04), particularly in those with multiple myeloma (P = .02). Moreover, mismatches for the ubiquitous Y chromosome-derived MiHAs resulted in a higher incidence of acute GVHD grade III-IV (P = .004), whereas autosomal MiHA mismatches, ubiquitous or restricted to hematopoietic cells, were not associated with severe GVHD. Finally, we found considerable differences among MiHAs in their capability of inducing in vivo T cell responses using dual-color tetramer analysis of peripheral blood samples collected after allo-SCT. Importantly, detection of MiHA-specific T cell responses was associated with improved relapse-free survival in recipients of sibling transplants (P = .01). Our findings provide a rationale for further boosting GVT immunity toward autosomal MiHAs with a hematopoietic restriction to improve outcomes after HLA-matched allo-SCT.
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Willemijn
authors.initials: W
authors.lastname: Hobo
authors.forename: Kelly
authors.initials: K
authors.lastname: Broen
authors.forename: Walter J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: Annelies
authors.initials: A
authors.lastname: Greupink-Draaisma
authors.forename: Niken
authors.initials: N
authors.lastname: Adisty
authors.forename: Yannick
authors.initials: Y
authors.lastname: Wouters
authors.forename: Michel
authors.initials: M
authors.lastname: Kester
authors.forename: Hanny
authors.initials: H
authors.lastname: Fredrix
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
authors.forename: Bert
authors.initials: B
authors.lastname: van der Reijden
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Frank
authors.initials: F
authors.lastname: Preijers
authors.forename: Ton
authors.initials: T
authors.lastname: Schattenberg
authors.forename: Ton
authors.initials: T
authors.lastname: Feuth
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Blijlevens
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Schaap
authors.forename: Harry
authors.initials: H
authors.lastname: Dolstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D055815:Young Adult