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Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood 2005 Jun 15;105(12):4878-84 PMID: 15731175 PMCID: PMC1894998

Pubmed ID

15731175

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.

Author List

Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, O'Reilly RJ, Horowitz MM, Dupont B

Author

Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-20444394742   347 Citations

MESH terms used to index this publication - Major topics in bold

Algorithms
Alleles
Bone Marrow Cells
Disease-Free Survival
Epitopes
Family Health
Female
Genotype
Graft Survival
HLA Antigens
HLA-B Antigens
HLA-C Antigens
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Killer Cells, Natural
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Ligands
Male
Myelodysplastic Syndromes
Oligonucleotide Probes
Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proportional Hazards Models
Receptors, Immunologic
Receptors, KIR
Recurrence
Retrospective Studies
Risk
T-Lymphocytes
Time Factors
Treatment Outcome
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5