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.
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.
Morishima
Yasuo
Y
Aichi Cancer Center Hospital, Department of Hematology and Cell Therapy, Nagoya, Japan. ymorisim@aichi-cc.jp <ymorisim@aichi-cc.jp>
Yabe
Toshio
T
Matsuo
Keitaro
K
Kashiwase
Koichi
K
Inoko
Hidetoshi
H
Saji
Hiroh
H
Yamamoto
Ken
K
Maruya
Etsuko
E
Akatsuka
Yoshiki
Y
Onizuka
Makoto
M
Sakamaki
Hisashi
H
Sao
Hiroshi
H
Ogawa
Seishi
S
Kato
Shunichi
S
Juji
Takeo
T
Sasazuki
Takehiko
T
Kodera
Yoshihisa
Y
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
D006680:HLA Antigens; D015236:HLA-C Antigens; D006682:HLA-DP Antigens; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR