尽管异基因造血干细胞移植(allo-HSCT)是血液系统恶性肿瘤的潜在治愈疗法,它可能与相关的移植后并发症有关。一些报道表明,免疫系统基因的多态性与移植后并发症的发展有关。在此背景下,这项工作的重点是识别细胞因子基因中的新多态性,并开发预测模型以预测发生移植物抗宿主病(GVHD)的风险,移植相关死亡率(TRM),复发和总生存期(OS)。
■我们的小组开发了一个132细胞因子基因组,在90例接受HLA相同同胞供体allo-HSCT的患者中进行了测试。使用贝叶斯逻辑回归(BLR)模型来选择最相关的变量。根据为每个模型选择的截止点,患者被分类为每种移植后并发症的高风险或低风险(aGVHDII-IV,aGVHDIII-IV,cGVHD,mod-sevcGVHD,TRM,复发和OS)。
■从定制组基因中选择了总共737种多态性。其中,在选择30个细胞因子基因(17个白细胞介素和13个趋化因子)的预测模型中包括41个多态性。在这些多态性中,5(12.2%)位于编码区,非编码区36个(87.8%)。所有模型具有P<0.0001的统计学显著性。
■总的来说,细胞因子基因的基因组多态性使得有可能预测allo-HSCT后研究的所有并发症的发展,因此,优化患者的临床管理。
UNASSIGNED: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS).
UNASSIGNED: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS).
UNASSIGNED: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001.
UNASSIGNED: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.