title: Bone marrow may be the preferable graft source in recipients homozygous for HLA-C group 2 ligands for inhibitory killer Ig-like receptors.
abstract: HLA class I molecules participate in natural killer cell regulation by acting as ligands for inhibitory killer cell Ig-like receptors (KIRs). One individual may express one or more inhibitory KIR lacking the corresponding HLA ligand. The role of this 'missing KIR ligand' constellation in hematopoietic SCT (HSCT) remains controversial and depends on incompletely defined transplant variables. We have retrospectively analyzed the effects of missing HLA-C group 1/2 and Bw4 KIR ligands in the recipients on the outcome in 382 HSCT, comparing 118 BMT to 264 PBSC transplants (PBSCT). In the multivariate Cox analysis of PBSCT, poor PFS was observed in homozygous HLA-C group 2 (C2/2) recipients (risk ratio (RR), 1.59; P=0.026). In contrast, C2 homozygosity was not unfavorable after BMT (RR, 0.68; P=0.16). C2 homozygous recipients (n=68) had better PFS after BMT than after PBSCT (RR, 0.17; P=0.001), due to fewer relapses (RR, 0.27; P=0.018). Missing Bw4 favorably influenced PFS after BMT (RR, 0.56; P=0.04), but not after PBSCT. These data suggest opposite effects of missing KIR ligands in BMT vs PBSCT. Larger studies are required to reassess whether BMT should be preferred to PBSCT as an option for C2/C2 recipients.
authors.affiliation: Department of Internal Medicine V, Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria. jo.clausen@salk.at
authors.forename: J
authors.initials: J
authors.lastname: Clausen
authors.forename: B
authors.initials: B
authors.lastname: Kircher
authors.forename: J
authors.initials: J
authors.lastname: Auberger
authors.forename: P
authors.initials: P
authors.lastname: Schumacher
authors.forename: C
authors.initials: C
authors.lastname: Grabmer
authors.forename: A
authors.initials: A
authors.lastname: Mühlbacher
authors.forename: G
authors.initials: G
authors.lastname: Gastl
authors.forename: D
authors.initials: D
authors.lastname: Nachbaur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow; D016026:Bone Marrow Transplantation; D002648:Child; D005260:Female; D015236:HLA-C Antigens; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D054340:Receptors, KIR; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR