Hematopoietic stem cell transplantation: killer immunoglobulin-like receptor component.
Recognition of recipient human leukocyte antigen (HLA) class I ligand by donor natural killer cell killer immunoglobulin-like receptors (KIR) has been proposed as the basis for donor allograft reactivity against malignancy leading to reduction in posttransplant relapse and higher survival for acute myelogenous leukemia. Analysis of KIR ligand effects in 1770 patients undergoing myeloablative T-replete hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors showed that lack of KIR ligand in patients for inhibitory KIR was associated with lower hazards of relapse in leukemia patients with in HLA-mismatched transplants [hazard ratio (HR): 0.061; 95% confidence interval (CI): 0.43-0.85; P-value = 0.004]. Absence of HLA-C group 2 or HLA-Bw4 KIR ligands were each associated with lower hazards of relapse (HR: 0.47; 95% CI: 0.28-0.79; P-value = 0.004; HR: 0.56; 95% CI: 0.33-0.97; P-value = 0.04, respectively). Based on these analyses, recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse following myeloablative HCT from unrelated donors. KIR genotyping for unrelated donors and recipients will clarify the role of these receptors in transplant outcome.
Hsu
K C
KC
Adult Allogeneic Blood and Marrow Transplantation Service, Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. hsuk@mskcc.org
Pinto-Agnello
C
C
Gooley
T
T
Malkki
M
M
Dupont
B
B
Petersdorf
E W
EW
D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D019520:Living Donors; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000628:therapy; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous
D015235:HLA-B Antigens; D015236:HLA-C Antigens; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR