title: Negative Impact of Unidirectional Host-versus-Graft Killer Cell Immunoglobulin-like Receptor Ligand Mismatch on Transplantation Outcomes after Unmanipulated Haploidentical Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia.
abstract: This study explored the influence of mismatched inhibitory killer cell immunoglobulin-like receptor (KIR) ligands on the outcome of haploidentical transplantation using T cell-replete, granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in adult patients with acute myeloid leukemia (AML). Three groups were examined: unidirectional graft-versus-host KIR ligand mismatched (GVH-KIR-MM; n = 33), bidirectional KIR ligand matched (KIR-M; n = 41), and unidirectional host-versus-graft KIR ligand mismatched (HVG-KIR-MM; n = 26). All recipients were treated with the same conditioning regimen (800 cGy total body irradiation, fludarabine, busulfan, and antithymocyte globulin). After a median follow-up of 26 months, the 2-year cumulative incidence of relapse was significantly higher in HVG-KIR-MM (40.3% ± 10.3%) versus others (18.9% ± 4.8%, P = .044). In the standard-risk group, the 2-year disease-free survival (DFS) was significantly lower in HVG-KIR-MM (51.8% ± 11.2%) compared with GVH-KIR-MM (88% ± 8.1%, P = .025). Multivariate analysis showed that HVG-KIR-MM was significantly associated with higher relapse (hazard ratio [HR], 10.7; P = .002) and lower DFS (HR, 3.4; P = .012). Subgroup analysis revealed increased DFS with higher doses of CD3(+)CD8(+) and CD3(-)CD56(+) grafts in GVH-KIR-MM (90.9% ± 8.7%, P = .006); there was no such effect in the other groups. Although our conclusions are limited by the absence of donor KIR genotype data, our study suggests unidirectional KIR ligand incompatibility in the host-versus-graft vector has a detrimental effect on T cell-replete haploidentical transplantation outcomes in adult patients with AML.
authors.affiliation: Department of Hematology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yahng
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Jeon
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Hematology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Cho
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ki-Seong
authors.initials: KS
authors.lastname: Eom
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Cancer Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: cumckim@catholic.ac.kr.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D006086:Graft vs Host Disease / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*; D055815:Young Adult
keywords: Acute myeloid leukemia; Haploidentical hematopoietic stem cell transplantation; Killer cell immunoglobulin–like receptor; T cell–replete