Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation(allo-HSCT).We retrospectively analyzed specific polymorphisms in g...Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation(allo-HSCT).We retrospectively analyzed specific polymorphisms in genes for interleukin(IL)-10,IL-6,tumor-necrosis factor alpha(TNF-α)and interferon gamma(IFN-c)in a pediatric cohort of 57 histocompatibility leucocyte antigen(HLA)-identical sibling myeloablative transplants.Both recipient and donor genotypes were tested for association with graft-versus-host disease(GVHD)by statistical methods including Cox regression analysis.We found a significant association between the IL-10 promoter haplotype polymorphisms at positions-1082,-819 and-592 with the occurrence of severe(grades Ⅲ–Ⅳ)acute GVHD(aGVHD).Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD(hazard risk(HR)50.20,95% confidence interval(CI):0.06–0.67)in comparison with patients with other IL-10 haplotypes(P50.008).Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype(HR50.17,95% CI:0.012–0.320)versus other IL-10 haplotypes(P=0.03),whereas overall survival was not influenced by IL-10 haplotype polymorphisms.In multivariate analysis,the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development(P=0.02,HR50.21,95% CI:0.05–0.78).These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.展开更多
文摘Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation(allo-HSCT).We retrospectively analyzed specific polymorphisms in genes for interleukin(IL)-10,IL-6,tumor-necrosis factor alpha(TNF-α)and interferon gamma(IFN-c)in a pediatric cohort of 57 histocompatibility leucocyte antigen(HLA)-identical sibling myeloablative transplants.Both recipient and donor genotypes were tested for association with graft-versus-host disease(GVHD)by statistical methods including Cox regression analysis.We found a significant association between the IL-10 promoter haplotype polymorphisms at positions-1082,-819 and-592 with the occurrence of severe(grades Ⅲ–Ⅳ)acute GVHD(aGVHD).Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD(hazard risk(HR)50.20,95% confidence interval(CI):0.06–0.67)in comparison with patients with other IL-10 haplotypes(P50.008).Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype(HR50.17,95% CI:0.012–0.320)versus other IL-10 haplotypes(P=0.03),whereas overall survival was not influenced by IL-10 haplotype polymorphisms.In multivariate analysis,the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development(P=0.02,HR50.21,95% CI:0.05–0.78).These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.
