Abstract
After allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor natural killer (NK) cells trigger alloreactions against potential recipient cells by their killer immunoglobulin-like receptors (KIRs). This study investigated whether KIR/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies. We studied KIR and HLA genotypes in 115 related donors and recipients (56 patients with AML and 59 patients with ALL) who had received allo-HSCT from HLA-matched sibling donors. We evaluated 17 KIR genes and some alleles, including their ligands, using the PCR-SSP assay. KIR gene frequency results between donors and recipients showed that donors had more activating KIR than their recipients. Chi-square comparison of KIR genotype frequencies in donors versus recipients revealed a significant difference (P < 0.001). We found a survival association between the donor lacking and the recipient having group B KIR haplotypes, although this was not statistically significant. This study suggests that we could exploit NK cell alloreactivity as a part of the optimization of donor selection and potential immunotherapeutic regimens to help facilitate good engraftment and reduce the risk of aGVHD incidence after allo-HSCT.
Highlights
Allogeneic hematopoietic stem cell transplantation is the definitive choice for treatment of highrisk hematologic malignancies, even in advanced stages [1,2]
This study investigated whether killer immunoglobulin-like receptors (KIRs)/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies
The potential benefit of the GVL effect relies on the elimination of residual malignant cells through immunological antitumor effects, induced by alloreactive T and natural killer (NK) cells, which leads to a lower relapse rate in allo-HSCT
Summary
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the definitive choice for treatment of highrisk hematologic malignancies, even in advanced stages [1,2]. There is evidence that allogeneic HLA-matched transplantation for patients with lymphoblastic and myeloblastic leukemia is more effective than autogeneic transplantation, because allo-HSCT may induce the graftversus-leukemia (GVL) effect [3,4]. The potential benefit of the GVL effect relies on the elimination of residual malignant cells through immunological antitumor effects, induced by alloreactive T and natural killer (NK) cells, which leads to a lower relapse rate in allo-HSCT. Acute GVHD, a major source of morbidity in HSCT, is mediated by donor allogeneic cytotoxic T cells against host tissues and leads to the recruitment of other effector cells including NK cells [9,10]. The pathophysiology of acute GVHD has been described as a three-phase phenomenon: activation of donor-derived T cells, effector phase through. Alloreactive donor NK cells facilitate engraftment by ablating different cells including residual leukemic cells, APCs, and T cells responsible for triggering GVHD [4,5,13,14,15]
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