title: Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.
abstract: Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation.
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Electronic address: bach0173@umn.edu.
authors.forename: Veronika
authors.initials: V
authors.lastname: Bachanova
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Division of Biostatistics and Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Anthony Nolan Research Institute, London, United Kingdom.
authors.forename: Steven G E
authors.initials: SGE
authors.lastname: Marsh
authors.affiliation: Center for Genetics & Center for Immunology and Vaccine Development, Children's Hospital of Oakland Research Institute, Oakland, California.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Haagenson
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.affiliation: Center for Genetics & Center for Immunology and Vaccine Development, Children's Hospital of Oakland Research Institute, Oakland, California.
authors.forename: Martha
authors.initials: M
authors.lastname: Ladner
authors.affiliation: Departments of Structural Biology and Microbiology and Immunology, Stanford University, Stanford, California.
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.affiliation: Departments of Structural Biology and Microbiology and Immunology, Stanford University, Stanford, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Cooley
mesh_terms: D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D054340:Receptors, KIR / Q000235:genetics*; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR
keywords: Allogeneic transplantation; Genotype; Killer immunoglobulin-like receptor; Natural killer (NK) cells; Non-Hodgkin lymphoma