title: Influence of killer immunoglobulin-like receptor/HLA ligand matching on achievement of T-cell complete donor chimerism in related donor nonmyeloablative allogeneic hematopoietic stem cell transplantation.
abstract: Achievement of complete donor chimerism (CDC) after allogeneic nonmyeloablative hematopoietic stem cell transplantation (NMHSCT) is important for preventing graft rejection and for generating a graft-vs-malignancy effect. The alloreactivity of NK cells and some T-cell subsets is mediated through the interaction of their killer immunoglobulin-like receptors (KIRs) with target cell HLA/KIR ligands. The influence of KIR matching on the achievement of T-cell CDC after NMHSCT has not been previously described. We analyzed 31 patients undergoing T-cell replete related donor NMHSCT following fludarabine and 200 cGy TBI. Recipient inhibitory KIR genotype and donor HLA/KIR ligand matches were used to generate an inhibitory KIR score from 1 to 4 based upon the potential number of recipient inhibitory KIRs that could be engaged with donor HLA/KIR ligands. Patients with a score of 1 were less likely to achieve T-cell CDC (P=0.016) and more likely to develop graft rejection (P=0.011) than those with scores greater than 1. Thus, patients with lower inhibitory KIR scores may have more active anti-donor immune effector cells that may reduce donor chimerism. Conversely, patients with greater inhibitory KIR scores may have less active NK cell and T-cell populations, which may make them more likely to achieve CDC.
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195, USA. sobeckr@ccf.org
authors.forename: R M
authors.initials: RM
authors.lastname: Sobecks
authors.forename: E J
authors.initials: EJ
authors.lastname: Ball
authors.forename: M
authors.initials: M
authors.lastname: Askar
authors.forename: K S
authors.initials: KS
authors.lastname: Theil
authors.forename: L A
authors.initials: LA
authors.lastname: Rybicki
authors.forename: D
authors.initials: D
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
authors.forename: S
authors.initials: S
authors.lastname: Andresen
authors.forename: B
authors.initials: B
authors.lastname: Pohlman
authors.forename: R
authors.initials: R
authors.lastname: Dean
authors.forename: J
authors.initials: J
authors.lastname: Sweetenham
authors.forename: R
authors.initials: R
authors.lastname: Macklis
authors.forename: L
authors.initials: L
authors.lastname: Bernhard
authors.forename: K
authors.initials: K
authors.lastname: Cherni
authors.forename: E
authors.initials: E
authors.lastname: Copelan
authors.forename: J P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: B J
authors.initials: BJ
authors.lastname: Bolwell
mesh_terms: D000328:Adult; D046528:Chimerism; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D054340:Receptors, KIR