title: Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor.
abstract: The responsible human leukocyte antigen (HLA) locus and the role of killer immunoglobulin-like receptor (KIR) ligand matching on transplantation outcome were simultaneously identified by multivariate analysis in 1790 patients with leukemia who underwent transplantation with T-cell-replete marrow from an unrelated donor (UR-BMT) through the Japan Marrow Donor Program. The graft-versus-leukemia (GVL) effect depended on leukemia cell type. HLA-C mismatch reduced the relapse rate in acute lymphoblastic leukemia (ALL) (hazard ratio [HR] = 0.47; P = .003), and HLA-DPB1 mismatch reduced it in chronic myeloid leukemia (CML) (HR = 0.35; P < .001). In contrast, KIR2DL ligand mismatch in the graft-versus-host (GVH) direction (KIR-L-MM-G) increased in ALL (HR = 2.55; P = .017). An increased rejection rate was observed in KIR2DL ligand mismatch in the host-versus-graft direction (HR = 4.39; P = .012). Acute GVH disease (GVHD) was increased not only in the mismatch of HLA-A, -B, -C, and -DPB1, but also in KIR-L-MM-G. As a whole, the mismatch of HLA-A, -B, and -DQB1 locus and KIR-L-MM-G resulted in increased mortality. In conclusion, not only the mismatch of HLA-C and -DPB1, but also KIR-L-MM-G affected leukemia relapse, which should be considered based on leukemia cell type. Furthermore, KIR-L-MM induced adverse effects on acute GVHD (aGVHD) and rejection, and brought no survival benefits to patients with T-cell-replete UR-BMT.
authors.affiliation: Aichi Cancer Center Hospital, Department of Hematology and Cell Therapy, Nagoya, Japan. ymorisim@aichi-cc.jp <ymorisim@aichi-cc.jp>
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Toshio
authors.initials: T
authors.lastname: Yabe
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Koichi
authors.initials: K
authors.lastname: Kashiwase
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Hiroh
authors.initials: H
authors.lastname: Saji
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Etsuko
authors.initials: E
authors.lastname: Maruya
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakamaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sao
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
authors.forename: Takeo
authors.initials: T
authors.lastname: Juji
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015236:HLA-C Antigens; D006682:HLA-DP Antigens; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000628:therapy*; D008024:Ligands; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D015236:HLA-C Antigens; D006682:HLA-DP Antigens; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR