title: Survival of AML patients receiving HLA-matched sibling donor allogeneic bone marrow transplantation correlates with HLA-Cw ligand groups for killer immunoglobulin-like receptors.
abstract: The reactivity of natural killer cells and some T-cell populations is regulated by killer immunoglobulin-like receptors (KIR) interactions with target cell HLA class I molecules. Such interactions have been suggested to influence outcomes after allogeneic hematopoietic stem cell transplantation, particularly for myeloid malignancies and with T-cell depletion. Donor KIR genotypes and recipient HLA KIR ligands were analyzed in 60 AML patients receiving T-cell replete, HLA-matched-related donor allogeneic bone marrow transplants. Patients were categorized according to their HLA inhibitory KIR ligand groups by determining whether or not they expressed: HLA-A3 or -A11; HLA-Bw4 and HLA-Cw groups (homozygous C1, homozygous C2 or heterozygous C1/C2). Heterozygous C1/C2 patients had significantly worse survival than those homozygous for C1 or C2 (5.8 vs 43.5 months, respectively, P=0.018) and the C1/C2 group had a higher relapse rate (47 vs 31%, respectively, P=0.048). Multivariate analysis found C1/C2 status to be an independent predictor for mortality (P=0.007, HR 2.54, confidence interval 1.29-5.00). C1/C2 heterozygosity was also associated with a delayed time to platelet engraftment, particularly for those with concurrent HLA-Bw4 expression (P=0.003). Since C1/C2 heterozygotes have a greater opportunity to engage inhibitory KIRs than do C1 or C2 homozygotes, they may more effectively inhibit KIR-positive NK- and T-cell populations involved in graft vs leukemia responses.
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: J P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: L A
authors.initials: LA
authors.lastname: Rybicki
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
authors.forename: B
authors.initials: B
authors.lastname: Pohlman
authors.forename: S
authors.initials: S
authors.lastname: Andresen
authors.forename: K S
authors.initials: KS
authors.lastname: Theil
authors.forename: R
authors.initials: R
authors.lastname: Dean
authors.forename: B J
authors.initials: BJ
authors.lastname: Bolwell
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D005260:Female; D020544:Graft vs Leukemia Effect; D015236:HLA-C Antigens / Q000096:biosynthesis*; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D015236:HLA-C Antigens