Role Of KIR Missing-self Model In Unrelated Donor Hematopoietic Stem Cell Transplantation:a Meta- Analysis

Background:Killer cell Immunoglobulin-like Receptors (KIRs) express on the surface of NK cell. It interact with human leukocyte antigen (HLA)-I molecule, which could deliver an activating or inhibitory signal to NK cell. As a result, NK cell function is activated or inhibited. When HLA-I molecular is not express or low express on the cell surface (tumor cell or infected cell), NK cell could be activated and attack the abnormity cells, because inhibitory KIRs could notrecognize the corresponding HLA-I molecular. KIR and its ligand match or mismatch between donor and patients influence the NK cell alloreactivity after unrelated hematopoietic stem cell transplantation (HSCT). And the donor-recipient ligand model was called "missing-self" model. Some researchers find that Donor-Recipient KIR ligand compatibility or incompatibility affects the prognosis of unrelated hematopoietic stem cell transplantation, but the conclusions were controversial. The goal of this study is to evaluate the prognostic effectiveness of Donor-Recipient KIR "missing self" model in unrelated donor HSCT.Method:We performed systematic literature searches in PubMed, Medline, Embase and The Cochrane Library, using the keywords "killer cell immunoglobulin like receptor/KIR" and "hematopoietic stem cell transplantation/HSCT" through Dec 2012. We searched articles published in English and other language. We choose studies according to the included criteria. Data needed to be extracted were:number of patients, mean age, level of HLA matching, diagnosis, stage of disease and the method of T cell depletion. Main Outcome Measurements were 5-year overall survival (OS), grade 2-4 acute graft versus host disease (a-GVHD),5-year transplantation/treatment-related mortality (TRM) and relapse.Results:One hundred and ninety-seven studies were searched, and 7 studies were included. A total of 3845 patients with hematopoietic disease received unrelated donor HSCT were involved. Pooled comparison between KIR ligand compatibility an in compatibility found that a higher 5-year OS rate (OR:odds ratio=1.93, CI:95% confidence interval=1.03-3.61, P=0.04); however, not differ in the incidence or grade 2-4 acute GVHD (OR=0.94, CI =0.71-1.24, P=0.64), relapse (OR=1.05, CI=0.75-1.47, P=0.77)and TRM (OR=0.61, CI =0.15-2.51, P=0.50).Conclusions:Our meta-analysis confirmed that incompatibility of KIR ligand in unrelated donor hematopoietic stem cell transplantation favor the 5-year OS. No effect on incidence of grade 2-4 a-GVHD, relapse and transplantation/treatment-related mortality has found. But such advantage probably influenced by HLA matching, T cell depletion and the characteristics of disease.