title: Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome.
abstract: Outcome of unrelated donor marrow transplantation is influenced by donor-recipient matching for HLA. Prior studies assessing the effects of mismatches at specific HLA loci have yielded conflicting results. The importance of high-resolution matching for all HLA loci has also not been established. We therefore examined the effects of HLA matching (low or high resolution or both) on engraftment, graft-versus-host disease (GVHD), and mortality in 1874 donor-recipient pairs retrospectively typed at high resolution for HLA-A, -B, -C, -DRB1, -DQ, and -DP. Mismatches at HLA-A, -B, -C, and -DRB1 each had similar adverse effects on mortality. Only HLA-A mismatches demonstrated significant adverse effects on GVHD. These adverse effects on outcome were more evident in transplants with low-resolution versus only high-resolution mismatches. Mismatches for HLA-DQ or -DP did not significantly affect outcome. When high-resolution mismatches at HLA-A, -B, -C, and -DRB1 were considered together, adverse effects on survival and GVHD were observed. We therefore conclude that matching for HLA-C should be incorporated into algorithms for unrelated donor selection. High-resolution mismatches at HLA-A, -B, -C, and -DRB1 adversely affect outcome, but less so than low-resolution mismatches. When clinical circumstances allow, high-resolution class I typing may help optimize donor selection and improve outcome.
authors.affiliation: Department of Medicine and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. neal.flomenberg@mail.tju.edu
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: Dennis
authors.initials: D
authors.lastname: Confer
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Vina
authors.forename: Alexandra
authors.initials: A
authors.lastname: Filipovich
authors.forename: Mary
authors.initials: M
authors.lastname: Horowitz
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hurley
authors.forename: Craig
authors.initials: C
authors.lastname: Kollman
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Harriet
authors.initials: H
authors.lastname: Noreen
authors.forename: Ann
authors.initials: A
authors.lastname: Begovich
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmeckpeper
authors.forename: Michelle
authors.initials: M
authors.lastname: Setterholm
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Williams
authors.forename: Edmond
authors.initials: E
authors.lastname: Yunis
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
mesh_terms: D000328:Adult; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000379:methods*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006680:HLA Antigens / Q000737:chemistry*; D015234:HLA-A Antigens / Q000737:chemistry; D015235:HLA-B Antigens / Q000737:chemistry; D015236:HLA-C Antigens / Q000737:chemistry* / Q000276:immunology; D006682:HLA-DP Antigens / Q000737:chemistry; D006683:HLA-DQ Antigens / Q000737:chemistry; D006684:HLA-DR Antigens / Q000737:chemistry; D059811:HLA-DRB1 Chains; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007938:Leukemia / Q000628:therapy; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II