The effect of missing KIR ligands, activating KIR genotype and haplotype on the outcome of T-cell-replete hematopoietic stem cell transplantation from HLA-identical siblings in Thai patients.
This study was a retrospective analysis of Thai patients undergoing T-replete hematopoietic stem cell transplant from human leukocyte antigen (HLA)-identical sibling donors. We investigated 66 patients, including 40 patients with acute myeloid leukemia (AML), 12 patients with acute lymphoblastic leukemia and 14 patients with chronic myeloid leukemia. Killer cell immunoglobulin-like receptor (KIR) genes and HLA ligands were typed by polymerase chain reaction-sequence specific oligonucleotide probes. We analyzed the effect of the number of missing KIR ligands (Bw4, C1 and C2) on clinical outcomes. A beneficial effect of missing KIR ligand was not observed in both univariate and multivariate analysis. When we analyzed the effect of specific missing KIR ligand on clinical outcomes, there was a trend that patients with missing A11 ligand had lower relapse rate (P = 0.076). Therefore, we also conducted the analysis by including the group with missing KIR ligands of Bw4, C1, C2 and A11. Patients with two or more than two missing KIR ligands had a trend for better clinical outcome including reduced relapse (P = 055) and statistically significant in terms of reduced acute graft-vs-host disease (aGVHD) rate (P = 0.013). In multivariate analysis, patients with two or more than two missing KIR ligands had a statistically significant better clinical outcome in terms of reduced aGVHD rate (HR = 0.155, 95%CI = 0.040-0.605, P = 0.007). The association between clinical outcome with KIR haplotypes, centromeric B haplotype and activating KIR was not observed here. Although the sample size in this study is rather limited, these data can later be subjected to meta-analysis to help reach the conclusion of the usefulness of this additional promising KIR genotyping in various hematopoietic stem cell transplantation types.
Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.|Histocompatibility and Immunogenetics Laboratory, National Blood Centre, Thai Red Cross Society, Bangkok, Thailand.
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Khanuntong
Histocompatibility and Immunogenetics Laboratory, National Blood Centre, Thai Red Cross Society, Bangkok, Thailand.
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Kuptawintu
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Upaisilpsathaporn
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Poolchareon
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Bunworasate
Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Hirankarn
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D015788:HLA-A1 Antigen / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D054340:Receptors, KIR / Q000145:classification / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D035781:Siblings; D013785:Thailand; D014019:Tissue Donors; D016896:Treatment Outcome
D015788:HLA-A1 Antigen; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; D054340:Receptors, KIR
HLA ligand; acute myeloid leukemia; graft-vs-host disease; killer cell immunoglobulin-like receptor