title: Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia.
abstract: Killer cell Ig-like receptors (KIRs) interact with HLA class I ligands to regulate NK cell development and function. These interactions affect the outcome of unrelated donor hematopoietic cell transplantation (HCT). We have shown previously that donors with KIR B versus KIR A haplotypes improve the clinical outcome for patients with acute myelogenous leukemia by reducing the incidence of leukemic relapse and improving leukemia-free survival (LFS). Both centromeric and telomeric KIR B genes contribute to the effect, but the centromeric genes are dominant. They include the genes encoding inhibitory KIRs that are specific for the C1 and C2 epitopes of HLA-C. We used an expanded cohort of 1532 T cell-replete transplants to examine the interaction between donor KIR B genes and recipient class I HLA KIR ligands. The relapse protection associated with donor KIR B is enhanced in recipients who have one or two C1-bearing HLA-C allotypes, compared with C2 homozygous recipients, with no effect due to donor HLA. The protective interaction between donors with two or more, versus none or one, KIR B motifs and recipient C1 was specific to transplants with class I mismatch at HLA-C (RR of leukemia-free survival, 0.57 [0.40-0.79]; p = 0.001) irrespective of the KIR ligand mismatch status of the transplant. The survival advantage and relapse protection in C1/x recipients compared with C2/C2 recipients was similar irrespective of the particular donor KIR B genes. Understanding the interactions between donor KIR and recipient HLA class I can be used to inform donor selection to improve outcome of unrelated donor hematopoietic cell transplantation for acute myelogenous leukemia.
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Steven G E
authors.initials: SG
authors.lastname: Marsh
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Haagenson
authors.forename: Koy
authors.initials: K
authors.lastname: Saeturn
authors.forename: Martha
authors.initials: M
authors.lastname: Ladner
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
mesh_terms: D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000401:mortality* / Q000628:therapy; D008297:Male; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D015996:Survival Rate; D061349:Unrelated Donors
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR
references.citation: Immunity. 1997 Dec;7(6):739-51
references.pmid: 9430220
references.citation: Blood. 2009 Dec 10;114(25):5182-90
references.pmid: 19828694
references.citation: Nat Immunol. 2003 Feb;4(2):175-81
references.pmid: 12496964
references.citation: Blood. 2008 Sep 15;112(6):2369-80
references.pmid: 18583565
references.citation: N Engl J Med. 2012 Aug 30;367(9):805-16
references.pmid: 22931314
references.citation: Blood. 2009 Jan 15;113(3):726-32
references.pmid: 18945962
references.citation: Science. 2002 Mar 15;295(5562):2097-100
references.pmid: 11896281
references.citation: Blood. 1999 Jul 1;94(1):333-9
references.pmid: 10381530
references.citation: J Immunol. 2012 Aug 1;189(3):1418-30
references.pmid: 22772445
references.citation: Br J Haematol. 2005 Nov;131(4):483-6
references.pmid: 16281939
references.citation: PLoS One. 2010 Dec 29;5(12):e15115
references.pmid: 21206914
references.citation: Blood. 2011 Jan 6;117(1):98-107
references.pmid: 20935255
references.citation: Br J Haematol. 2011 Oct;155(1):14-29
references.pmid: 21812770
references.citation: Mol Immunol. 2002 May;38(14):1007-21
references.pmid: 11955593
references.citation: J Immunol. 2002 Jul 1;169(1):239-47
references.pmid: 12077250
references.citation: J Immunol. 1998 Jul 15;161(2):571-7
references.pmid: 9670929
references.citation: J Immunol. 1997 Jun 1;158(11):5237-41
references.pmid: 9164941
references.citation: Curr Opin Oncol. 2007 Mar;19(2):142-7
references.pmid: 17272987
references.citation: Blood. 2003 Aug 1;102(3):814-9
references.pmid: 12689936
references.citation: Biol Blood Marrow Transplant. 2006 Aug;12(8):876-84
references.pmid: 16864058
references.citation: Blood. 2007 Jul 1;110(1):433-40
references.pmid: 17371948
references.citation: Immunogenetics. 2010 Dec;62(11-12):729-40
references.pmid: 20878401
references.citation: J Exp Med. 1995 Mar 1;181(3):1133-44
references.pmid: 7532677
references.citation: Eur J Immunol. 2004 Jun;34(6):1673-9
references.pmid: 15162437
references.citation: J Immunol. 2007 Jan 1;178(1):33-7
references.pmid: 17182537
references.citation: Immunogenetics. 2009 Oct;61(10):663-71
references.pmid: 19789864
references.citation: Blood. 2010 Oct 7;116(14):2411-9
references.pmid: 20581313
references.citation: Blood. 2004 Feb 15;103(4):1521-6
references.pmid: 14504099
references.citation: Blood. 2010 Apr 15;115(15):3162-5
references.pmid: 20124216
references.citation: Curr Opin Immunol. 2008 Oct;20(5):588-93
references.pmid: 18674615
references.citation: Biol Blood Marrow Transplant. 2006 Aug;12(8):828-36
references.pmid: 16864053
references.citation: J Immunol. 2008 Mar 15;180(6):3969-79
references.pmid: 18322206
references.citation: Mol Immunol. 2005 Feb;42(4):531-4
references.pmid: 15607809
references.citation: Blood. 2010 Feb 11;115(6):1166-74
references.pmid: 19903900
references.citation: Blood. 2010 Nov 11;116(19):3853-64
references.pmid: 20696944
references.citation: J Immunol. 2013 Jun 15;190(12):6198-208
references.pmid: 23686481
references.citation: Immunogenetics. 2007 Jul;59(7):525-37
references.pmid: 17464504