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HLA-DQB1 错配独立增加异基因造血干细胞移植受者严重出血风险。

HLA-DQB1 mismatch increase risk of severe bleeding independently in recipients of allogeneic stem cell transplant.

机构信息

Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215000, China.

Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

出版信息

Ann Hematol. 2021 Sep;100(9):2351-2361. doi: 10.1007/s00277-021-04520-0. Epub 2021 Apr 12.

DOI:10.1007/s00277-021-04520-0
PMID:33846855
Abstract

Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31-3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54-48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients.

摘要

严重出血是异基因造血干细胞移植(allo-HSCT)后移植物抗宿主病(GVHD)导致急性白血病(AL)患者死亡的主要原因。然而,在队列研究中尚未报道与 HSCT 相关的 GVHD 患者严重出血的预后价值和预测。我们对 2014 年 2 月 1 日至 2015 年 12 月 1 日接受 allo-HSCT 后发生 GVHD 的 200 例 AL 患者进行了回顾性分析。多变量分析表明,严重出血等级与死亡风险相关(HR 2.26,95%CI 1.31-3.92,p<0.001***)。为了预测严重出血并找到出血事件的解决方案,我们建立了一个多因素逻辑回归模型。HLA-DQB1 不匹配、巨核细胞重建失败和 III 或 IV 级 GVHD 是严重出血的独立危险因素。在所有这些变异中,HLA-DQB1 的比值比(OR)最高(OR:16.02,95%CI:11.54-48.68)。将 HLA-DQB1 添加到其他因素中可以提高预测严重出血的重新分类(NRI=0.195,z=2.634,p=0.008**;IDI=0.289,z=3.249,p<0.001***)。Lasso 回归用于选择变量。生成并显示了逻辑模型的列线图。校准曲线在估计严重出血方面表现出优异的准确性(C 指数为 0.935)。HLA-DQB1 显示出对 HSCT 患者严重出血预测的优异效果。

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Br J Clin Pharmacol. 2019 Dec;85(12):2689-2693. doi: 10.1111/bcp.14105. Epub 2019 Dec 13.
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Ann Clin Transl Neurol. 2019 Sep;6(9):1849-1857. doi: 10.1002/acn3.50884. Epub 2019 Aug 30.
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Reduced intensity allogeneic stem cell transplant with anti-thymocyte globulin and post-transplant cyclophosphamide in acute myeloid leukemia.抗胸腺细胞球蛋白和移植后环磷酰胺联合减低强度异基因造血干细胞移植治疗急性髓系白血病。
Eur J Haematol. 2019 Nov;103(5):510-518. doi: 10.1111/ejh.13321. Epub 2019 Sep 9.
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