P006 NK KIR receptor genotypes are associated with relapse in mexican HLA matched sibling patients with acute lymphoblastic leukemia (ALL)

Aim The outcome of Hematopoietic Stem Cell Transplantation (HSCT) is strongly associated with the HLA identity of donor/recipient, and GVHD remains the most frequent associated factor with mortality and impact on the quality of life. A successful HSCT depends also on T-cell mediated graft vs. leukemia (GvL) effect. Relapse is a major important challenge. NK cells, KIR and their HLA ligands are involved with an increase in overall survival, as well as better engraftment and reduced incidence of GVHD in patients with AML. The aim of the study was to determine the KIR gene content, their HLA ligands and their association on the outcome of ALL patients transplanted with HLA-identical sibling donors. Methods Twenty-seven Mexican patients with their HLA-identical siblings were included. Of these, 20 had ALL and 7 AML. KIR gene content was determined with the LinkSēq™ KIR kit and was run on an ABI 7500 Real-Time PCR instrument. Analysis was done with SureTyper 5. HLA intermediate resolution typing was performed by SSOP on a Luminex. HLA alleles were analyzed with the Match it DNA 1.2.0 software. KIR haplotypes and HLA ligands were assessed using https://www.ebi.ac.uk/ipd/kir/ligand.html . Allele Frequency (AF) and multiple parameter comparison analysis was performed using the SPSS17 software. Results We looked if activating or inhibitory KIR genes had any effect on relapse, long term disease free survival (DFS), GVHD or mortality. An association with relapse was observed in ALL patients, when the matched sibling donor carried the 3DL1 -Bw4 ligand (50% of ALL patients were carriers); (Chi2 = 5.93; p = 0.03) with no differences in Bw4 80I and 80T ligand. The AA and Bx haplotypes did not have any association with mortality, GVHD, relapse or DFS. Conclusions The results in ALL regarding relapse show that the presence of 3DL1 -Bw4, conveys higher susceptibility for relapse, as shown for AML. Contrary to AML, no effect was detected with 80I or 80T with intermediate relapse and mortality, implying a non benefit of education and sensitivity to inhibition as reported for AML. More cases of ALL are being analyzed to confirm if HLA and KIR allele typing in donor selection, enables the antileukemic benefits of NK alloreactivity in HSCT, in ALL, as it has been pointed out in AML, since the affected cell population in ALL, is totally different of the latter.