KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy Journal Article


Authors: Hsu, K. C.; Gooley, T.; Malkki, M.; Pinto-Agnello, C.; Dupont, B.; Bignon, J. D.; Bornhauser, M.; Christiansen, F.; Gratwohl, A.; Morishima, Y.; Oudshoorn, M.; Ringden, O.; van Rood, J. J.; Petersdorf, E.
Article Title: KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy
Abstract: Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval, .043-0.85; P = .004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P = .004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P = .04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P = .95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants. © 2006 American Society for Blood and Marrow Transplantation.
Keywords: controlled study; treatment outcome; disease-free survival; survival rate; transplantation, homologous; acute granulocytic leukemia; major clinical study; cancer recurrence; follow-up studies; t lymphocyte; t-lymphocytes; genotype; risk factors; relapse; recurrence; hematopoietic stem cell transplantation; chronic myeloid leukemia; prediction; acute lymphoblastic leukemia; risk assessment; confidence interval; homozygosity; hematologic malignancy; hla matching; myelodysplastic syndrome; donor; hematologic neoplasms; antigen recognition; epitope; hla-c antigens; ligands; killer cells, natural; cancer relapse; living donors; killer cell immunoglobulin like receptor; receptors, kir; lymphatic leukemia; hla b antigen; hla c antigen; isoantigens; hla-b antigens; receptors, immunologic; alloimmunity; epitopes; recipient; myeloid leukemia; nonmyeloablative stem cell transplantation; lymphocyte transfusion; major histocompatibility antigen; minor histocompatibility antigen; kir ligand; histoincompatibility; unrelated hematopoietic cell transplantation
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 12
Issue: 8
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2006-08-01
Start Page: 828
End Page: 836
Language: English
DOI: 10.1016/j.bbmt.2006.04.008
PUBMED: 16864053
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 65" - "Export Date: 4 June 2012" - "CODEN: BBMTF" - "Source: Scopus"
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MSK Authors
  1. Katharine C Hsu
    152 Hsu
  2. Bo Dupont
    197 Dupont