**8. Donor selection based on killer cell immunoglobulin-like receptor typing**

Since alloreactive NK cells play a critical role in the successful treatment of leukemia patients receiving alloreactive grafts, it is crucial to ensure sufficient number of NK cells in the best possible donor. As we have discussed above, the polymorphisms of KIR and its ligand HLA obviously affect NK cell alloreactivity. Therefore, genotyping of these two families of genes provides the probability to identify the size of alloreactive NK cell populations in donor. Up to now, there are three levels of KIR typing. The first level is genotyping to test the gene content of KIR families [159]. Based on these results, the KIR haplotype of donor is confirmed and scored. The preferable donors defined in this level are those possess inhibitory KIR specific for HLA-I alleles absent in the recipients with highest haplotype B score [128, 160]. The second level of KIR typing is using flow cytometry and quantitative PCR to assess the number of KIR mismatched NK cells and the expression of KIR gene [125]. Based on the results of this level, the donors possess the largest number of KIR mismatched NK cells with high frequency of KIR gene expression are preferable. The third level is KIR typing of alleles [161]. As we have discussed above, different alleles of KIR gene may result in different intensity of NK cell alloreactivity. Therefore, donors with stronger KIR alleles should be selected. Finally, FcγR polymorphisms are also needed to analyze when the treatment is associated with ADCC effect of NK cells [162]. Additionally, the assess of NK cell cytotoxicity toward leukemic blasts from patients could also help to predict the outcome of HSCT.
