الفهرس 
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Abstract
Successful allogeneic HSCTdepends also on T-cell mediated GVL effect, in which donor-derived T cells clear the remaining leukemic cells in patient. In addition to alloreactive T cells, donor-derived natural killer (NK) cells are able to kill malignant or virus-infected cells in the patient. NK cells have a crucial role in relapse prevention by destroying remaining acute myeloid leukemia cells .Natural killer cells are regulated by their surface receptors KIR, which have either activating or inhibitory function by interacting with HLA class I, HLA-C alleles and Bw4 alleles, present on normal cell surface.Fifteen KIR genes can be categorized into inhibitory (KIR A-haplotype) or activating haplotypes (KIR B haplotype) based on their gene content .These haplotypes can be further divided as telomeric and centromeric parts, which contain either A- or B-motifs according to the presence or absence of A- or B-haplotype defining KIR genes.Studies showed that acute myeloid leukemia (AML) patients benefit from the KIR-ligand mismatch due to the “missing self”phenomenon. In addition, there is evidence that the risk of relapse is reduced in those AML patients whose donors have several activating KIR genes or KIR-B gene-motifs in unrelated donor HSCT Aim. The aim of the study was to assess the impact of natural killer cells receptors KIRs and their HLA-class I (mainly HLA-C alleles) on various outcomes in Egyptian patients receiving HSCT from an HLA matched sibling donor. Materials and methods The study included 65 patient/donor pairs who received PBSCT from HLA-matched identical siblings at Nasser Institute, Ministry of Health, Egypt, in the period between 2010 and 2014. KIR genotyping was done for all donors and HLA-C genotyping was done for all patients. KIR genotyping was done using reverse sequence specific oligonucleotide probes (rSSO) coupled with luminex technology for detection. HLA-C genotyping was done using rSSO strip assay. Results KIR genotyping showed presence of all four framework genes (2DL4.3DL2.3DL3.3DP1). The most frequent KIR genes were 2DL1 (100%), 2DS4(86.2%) and 2DL3(70.8%).Most frequent KIR haplotype was B/x 55/65 (84.6%) while A/A haplotype frequency was 10/65(15.4%). The most frequent KIR ligand wasHLA-C07; 28/130(21.5%). Relapse was observed in 6/65(9.2%) patients.2DS4 was the only KIR gene with significant impact on reduced risk of relapse (p=0.002).A trend towards reduced risk of relapse was observed with more than two CenBmotifs (p=0.09), while another towards increased relapse wasassociated with homozygous HLA-C2 ligands (p=0.07) but did not achieve statistical significance. Six/65(9.2%) patients developed CMV infection that was detected by PCR. KIR 2DL5 was associated with reduced CMV infection (p=0.03).No association was observed forany other KIR gene, haplotype or ligand with CMV infection. Acute GVHD Grade 0-I was observed in 54/65 (83%) and Grade II-IV in 11/65 (16.9%) patients. As for chronic GVHD (cGVHD), 55/65 (84%) showed no signs of GVHD, 5/65 (7.6%) showed mild and 5/65 (7.6%) showed moderate cGVHD. Activating KIR 2DS2 showed increased risk of GVHD (p=0.009).No other KIR gene, haplotype or ligand was associated with GVHD. Activating KIR 2DS3 was associated with rapid leukocyte engraftment (p=0.02), inhibitory KIR 2DL5 was associated with rapid platelets engraftment (p=0.05) while inhibitory KIR 3DL1 showed a trend associated with rapid leukocyte engraftment (p=0.06), though it did not achieve statistical significance. There was no significant association of any KIR genes or haplotypes with overall survival however a trend towards decreased survival was associated with homozygous HLA-C (C1/C1,C2/C2) alleles as compared to heterozygous HLA-C1/C2, though it did not reach statistical significance.