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首页> 外文期刊>International journal of immunogenetics >Impact of genomic risk factors on survival after haematopoietic stem cell transplantation for patients with acute leukaemia
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Impact of genomic risk factors on survival after haematopoietic stem cell transplantation for patients with acute leukaemia

机译：基因组危险因素对急性白血病患者造血干细胞移植后存活的影响

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The EBMT risk score is an established tool successfully used in the prognosis of survival post-HSCT and is applicable for a range of haematological disorders. One of its main advantages is that score generation involves summation of clinical parameters that are available pretransplant. However, the EBMT risk score is recognized as not being optimal. Previous analyses, involving patients with various diagnoses, have shown that non-HLA gene polymorphisms influence outcome after allogeneic HSCT. This study is novel as it focuses only on patients having acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene polymorphisms can be added to the EBMT risk score in a Cox regression model to improve prognostic ability for overall survival. The results of the study found that three genetic factors improved EBMT risk score. The presence of MAL (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of heat- shock protein 70-hom (+2437) (rs2227956) allele C in the patient were associated with decreased survival time. When compared to the EBMT risk score, the scores combining EBMT risk score with the genetic factors had an improved correlation with clinical outcome and better separation of risk groups. A bootstrapping technique, involving repeated testing of a model using multiple validation sets, also revealed that the newly proposed model had improved predictive value when compared to the EBMT risk score alone. Results support the view that non-HLA poly-morphisms could be useful for pretransplant clinical assessment and provide evidence that polymorphisms in the recipient genotype may influence incoming donor cells, suppressing the initiation of the graft versus leukaemia effect and reducing survival.
机译：EBMT风险评分是已成功用于HSCT术后预后的既定工具，适用于一系列血液疾病。它的主要优点之一是评分生成涉及移植前可用的临床参数的总和。但是，EBMT风险评分被认为不是最佳的。先前对涉及各种诊断的患者的分析表明，非HLA基因多态性会影响同种异体HSCT的预后。这项研究是新颖的，因为它仅针对患有急性白血病（N = 458）的患者，并试图证明如何在Cox回归模型中将非HLA基因多态性添加到EBMT风险评分中，以改善整体生存的预后能力。研究结果发现，三个遗传因素可改善EBMT风险评分。患者中存在MAL（rs8177374）等位基因T，患者中不存在糖皮质激素受体单倍型（由rs6198，rs33389和rs33388组成）ACT，并且不存在热激蛋白70-hom（+2437）（rs2227956）等位基因C患者的生存时间减少。与EBMT风险评分相比，将EBMT风险评分与遗传因素相结合的评分与临床结局具有更好的相关性，并且可以更好地分离风险组。一种自举技术，其中涉及使用多个验证集对模型进行重复测试，还显示与单独的EBMT风险评分相比，新提出的模型具有更高的预测价值。结果支持非HLA多态性可用于移植前临床评估的观点，并提供了证据，表明受体基因型中的多态性可能影响传入的供体细胞，抑制了移植物抗白血病作用的开始并降低了存活率。

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