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Post-Transplant Events

Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors

Abstract

We evaluated the influence of gene polymorphisms of TLR9 (T1237C; T1486C), IL23R (A1142G), and NOD2 SNP8 (R702W), SNP12 (G908R) and SNP13 (1007fs) on outcome of hematopoietic SCT in a homogenous group of 142 AML patients after non-T-cell-depleted myeloablative transplantation from HLA-identical sibling donors. In our retrospective study, we found that TLR9 gene variant at 1486 influenced transplant outcome. Estimated 5-year OS in patients with the CC gene variant of TLR9 was 70.2% compared with 44.8% (P<0.027) in patients with TC/TT of TLR9 gene. No significant influences on 5-year OS were found for gene polymorphisms of NOD2 or IL23R (A1142G) in this study group. The 5-year treatment-related mortality was lowest in patients with CC gene variant of TLR9 (7.8 vs 23.1%; NS). Acute GVHD grade III–IV was higher in patients with NOD2 gene variants (28 vs 12.8%; P=0.065). In contrast, patients transplanted from donors with the gene variant of IL23R had no occurrence of severe acute GVHD grade III–IV (0 vs 18.4%; P<0.048). However, multivariate analysis confirmed the influence of NOD2 gene variants on the occurrence of acute GVHD grade II–IV after transplant. These results suggest that the gene variants of TLR9, NOD2 and Il23R had influence on the outcome of transplant.

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Acknowledgements

We thank Silke Gottwald, Christiane Schary (all Essen, Germany) for their excellent technical assistance with genotyping analyses. This work was supported by grants from the Deutsche Krebshilfe 70-3093-El4 and Kulturstiftung Essen (05 032 Elmaagacli).

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Correspondence to A H Elmaagacli.

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Elmaagacli, A., Steckel, N., Ditschkowski, M. et al. Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors. Bone Marrow Transplant 46, 702–708 (2011). https://doi.org/10.1038/bmt.2010.166

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