title: Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors.
abstract: The impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft-versus-host disease (GVHD) and graft failure after reduced-intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50% in those with two- to three-loci-mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II-IV aGVHD (P=0.01), chronic GVHD (cGVHD) (P=0.05) and graft failure (P=0.033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one-locus-mismatched RICT (51%) and HLA-matched RICT (48%) (P<0.0001). A two- to three-loci mismatch was identified as an independent risk factor for OS (P<0.001), but there was no significant difference in OS between HLA-matched and one-locus-mismatched RICT. HLA incompatibility between the donor and recipient is an important risk factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients with high-risk malignancies who lack HLA-matched related donors.
authors.affiliation: Centre for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan. tteshima@cancer.med.kyushu-u.ac.jp
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kosei
authors.initials: K
authors.lastname: Matsue
authors.forename: Fumio
authors.initials: F
authors.lastname: Kawano
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Wake
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ishida
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kasai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
mesh_terms: D000208:Acute Disease; D002908:Chronic Disease; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents