engleski

KIR GENES AS ADDITIONAL FACTORS IN DONOR SELECTION FOR HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATIONS

Haploidentical hematopoietic stem cell transplantation (HSCT) outcome depends highly on selection of a best donor which can be improved by including additional factors such as killer immunoglobulin-like receptors (KIR) into consideration. This retrospective study involved 52 patients (P) and their donors (D) in the haplo-HSCT program in UHC Zagreb who were analyzed for different models of KIR impact on HSCT outcome. Effects of KIR ligand-ligand mismatch (MM), KIR inhibitory receptor-ligand MM in GvH direction, KIR AA/Bx haplotype, number of activating KIR (aKIR) genes and presence of specific aKIR gene in the donor on overall survival (OS) and relapse incidence were estimated. No difference in KIR gene distribution between P and D was observed but three aKIR (2DS1, 2DS5, 3DS1) genes had significantly higher frequency among P (P=0.039 ; P=0.005 ; P=0.010) and D (P=0.010 ; P=0.048 ; P=0.010) in comparison to their frequencies in the Croatian population. Lower occurrence of KIR haplotype AA and higher occurrence of haplotype Bx was revealed among P (AA- 25.0% ; Bx-75.0%) and D (AA-28.8% ; Bx-71.2%) when compared to controls (AA-33.6% ; Bx-66.4%). Fifteen P-D pairs (28.8%) shared identical KIR genotypes. In the remaining 37 pairs (71.2%) that differed in KIR genotype combinations, the P-D KIR haplotype combination with highest frequency was Bx(P)/Bx(D) (59.6%) while all other combinations were similarly represented (AA(P)/AA(D)- 13.5% ; AA(P)/Bx(D)-11.5% ; Bx(P)/AA(D)-15.4%). All P-D pairs had at least 1 KIR ligand MM with the highest percent of those with 2 MM (38.5%). The OS rate for the whole cohort was 57.7% with 30.8% of relapse incidence (median follow-up time of 355 days). None of investigated variables had significant impact on OS or relapse incidence in univariate and multivariate analyses. Obtained results might be in part explained by small sample size, so further evaluation on larger transplant cohort is required to define the KIR impact on haplo HSCT outcome.

KIR genes, haploidentical HSCT

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