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用于预测异基因造血细胞移植后临床结局的变量选择方法。

Variable selection methods for predicting clinical outcomes following allogeneic hematopoietic cell transplantation.

机构信息

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

出版信息

Sci Rep. 2021 Feb 5;11(1):3230. doi: 10.1038/s41598-021-82562-0.

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for a large number of diseases. However, the greatest barriers to the success of allo-HCT are relapse and graft-versus-host-disease (GVHD). Many studies have examined the reconstitution of the immune system after allo-HCT and searched for factors associated with clinical outcome. Serum biomarkers have also been studied to predict the incidence and prognosis of GVHD. However, the use of multiparametric immunophenotyping has been less extensively explored: studies usually focus on preselected and predefined cell phenotypes and so do not fully exploit the richness of flow cytometry data. Here we aimed to identify cell phenotypes present 30 days after allo-HCT that are associated with clinical outcomes in 37 patients participating in a trial relating to the prevention of GVHD, derived from 82 flow cytometry markers and 13 clinical variables. To do this we applied variable selection methods in a competing risks modeling framework, and identified specific subsets of T, B, and NK cells associated with relapse. Our study demonstrates the value of variable selection methods for mining rich, high dimensional clinical data and identifying potentially unexplored cell subpopulations of interest.

摘要

异基因造血细胞移植(allo-HCT)是治疗多种疾病的潜在根治方法。然而,allo-HCT 成功的最大障碍是复发和移植物抗宿主病(GVHD)。许多研究已经研究了 allo-HCT 后免疫系统的重建,并寻找与临床结果相关的因素。也研究了血清生物标志物来预测 GVHD 的发生率和预后。然而,多参数免疫表型分析的应用尚未得到广泛探索:研究通常集中于预先选择和预先定义的细胞表型,因此不能充分利用流式细胞术数据的丰富性。在这里,我们旨在确定 37 名参与 GVHD 预防试验的患者在 allo-HCT 后 30 天存在的与临床结果相关的细胞表型,这些患者来自 82 个流式细胞术标志物和 13 个临床变量。为此,我们在竞争风险建模框架中应用了变量选择方法,并确定了与复发相关的特定 T、B 和 NK 细胞亚群。我们的研究证明了变量选择方法在挖掘丰富的高维临床数据和识别潜在未探索的感兴趣的细胞亚群方面的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1600/7865009/1f443ac007c5/41598_2021_82562_Fig1_HTML.jpg

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