Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes Journal Article


Authors: Hsu, K. C.; Keever-Taylor, C. A.; Wilton, A.; Pinto, C.; Heller, G.; Arkun, K.; O'Reilly, R. J.; Horowitz, M. M.; Dupont, B.
Article Title: Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes
Abstract: Inhibitory killer immunoglobulin (Ig)-like receptors (KIRs) recognize HLA-C and -B epitopes on target cells, thereby regulating natural killer (NK) cell activity. In 178 patients receiving T-cell-depleted HLA-identical sibling transplants for acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS), analysis of donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients lacked an HLA ligand for donor-inhibitory KIR. Lack of HLA ligand for donor-inhibitory KIR (missing KIR ligand) had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for CML and ALL. In patients with AML and MDS, however, there was a significant missing KIR ligand effect on DFS (P = .014; hazard ratio [HR], 0.53; 95% confidence interval [95% CI], 0.28-0.88) and OS (P = .03; HR, 0.53; 95% CI, 0.3-0.93). Incidence of relapse was also lower in patients with AML and MDS who lacked the HLA ligand for donor-inhibitory KIR (P = .04; HR, 0.41; 95% CI, 0.18-0.97). AML and MDS patients lacking 2 HLA ligands for donor-inhibitory KIR had the highest DFS (P = .002) and OS (P = .003). There was no significant contribution of donor-activating KIR to transplantation outcome in these patients. These data indicate that the absence of class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcome in HLA-identical sibling transplantation and that the lack of HLA-C or -B ligands for donor-inhibitory KIR can contribute to improved outcomes for patients with AML and MDS. © 2005 by The American Society of Hematology.
Keywords: survival; controlled study; treatment outcome; disease-free survival; retrospective studies; unclassified drug; acute granulocytic leukemia; major clinical study; polymerase chain reaction; t-lymphocytes; bone marrow cells; family health; proportional hazards models; genotype; alleles; relapse; recurrence; hematopoietic stem cell transplantation; chronic myeloid leukemia; algorithms; acute lymphoblastic leukemia; time factors; risk; myelodysplastic syndrome; antigen specificity; hla-c antigens; hematopoietic stem cells; ligands; natural killer cell; killer cells, natural; graft survival; t cell depletion; hla b antigen; hla c antigen; hla-b antigens; hla antigens; lymphocyte antigen receptor; myelodysplastic syndromes; receptors, immunologic; hla system; alloimmunity; epitopes; leukemia, myelocytic, acute; leukemia, myeloid, chronic; leukemia, lymphocytic, acute; oligonucleotide probes; protein killer immunoglobulin like receptor
Journal Title: Blood
Volume: 105
Issue: 12
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2005-06-15
Start Page: 4878
End Page: 4884
Language: English
DOI: 10.1182/blood-2004-12-4825
PUBMED: 15731175
PROVIDER: scopus
PMCID: PMC1894998
DOI/URL:
Notes: --- - "Cited By (since 1996): 194" - "Export Date: 24 October 2012" - "CODEN: BLOOA" - "Source: Scopus"
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Citation Impact
MSK Authors
  1. Andrew Wilton
    27 Wilton
  2. Glenn Heller
    353 Heller
  3. Katharine C Hsu
    149 Hsu
  4. Richard O'Reilly
    583 O'Reilly
  5. Bo Dupont
    196 Dupont
  6. Knarik Arkun
    8 Arkun
  7. Caren Rollins Pinto
    2 Pinto