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评估接受他克莫司的小儿造血干细胞移植患者发生急性移植物抗宿主病的风险因素。

Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus.

机构信息

Department of Pharmacy Practice, Chapman University School of Pharmacy, Irvine, California, USA.

The Hyundai Cancer Institute, CHOC Children's Hospital, Orange, California, USA.

出版信息

Clin Transl Sci. 2021 Jul;14(4):1303-1313. doi: 10.1111/cts.12982. Epub 2021 Apr 8.

DOI:10.1111/cts.12982
PMID:33503293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8301588/
Abstract

To identify the clinical and pharmacological risk factors associated with tacrolimus pharmacodynamics for acute graft-versus-host disease (aGVHD) in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. A retrospective cohort single center chart review study was conducted with pediatric patients who received tacrolimus prophylaxis after allogeneic HSCT between January 1, 2017, and December 31, 2019. Potential risk factors were tested separately between aGVHD and non-aGVHD cohorts and were further analyzed in a logistic regression model with backward elimination and a partial least squares discriminant analysis. Thirty-three patient cases were included in our study and 52% (17/33) developed aGVHD while on tacrolimus prophylaxis. When tested independently, donor age and sibling versus parent donor/recipient relation were shown to be statistically significant between aGVHD and non-aGVHD patients (p < 0.005). Pharmacological factors associated with tacrolimus treatment failed to demonstrate a significant impact on patient's risk of aGVHD. Using a best fit logistic regression model that tested all the variables together, donor age was the only significant variable predicting patient's risk of aGVHD (p < 0.01). Donor relationship and donor age were unable to be evaluated separately and are therefore confounding variables. Among pediatric patients receiving allogeneic HSCT, aGVHD risk is significantly decreased by either sibling donor and/or younger donors. Although no conclusions were drawn on the effect of tacrolimus therapy (p = 0.08), results warrant additional research with a larger sample size to evaluate the accuracy of monitoring tacrolimus serum trough levels.

摘要

目的

确定与接受亲缘相合供体异基因造血干细胞移植(HSCT)的儿科患者他克莫司治疗急性移植物抗宿主病(aGVHD)的药代动力学相关的临床和药理学风险因素。

方法

本研究为回顾性队列单中心图表回顾研究,纳入 2017 年 1 月 1 日至 2019 年 12 月 31 日期间接受异基因 HSCT 后接受他克莫司预防治疗的儿科患者。在 aGVHD 和非 aGVHD 队列之间分别测试潜在风险因素,并通过向后消除和偏最小二乘判别分析进行逻辑回归模型分析。

结果

本研究共纳入 33 例患者,52%(17/33)在接受他克莫司预防治疗时发生 aGVHD。当单独测试时,供体年龄和供体与受体为同胞关系与非 aGVHD 患者之间存在统计学显著差异(p<0.005)。与他克莫司治疗相关的药理学因素未能显示对患者发生 aGVHD 的风险有显著影响。使用一起测试所有变量的最佳拟合逻辑回归模型,供体年龄是唯一预测患者发生 aGVHD 风险的显著变量(p<0.01)。供体关系和供体年龄无法单独评估,因此是混杂变量。在接受异基因 HSCT 的儿科患者中,同胞供体和/或年轻供体可显著降低 aGVHD 风险。尽管尚未得出关于他克莫司治疗效果的结论(p=0.08),但结果表明需要进一步研究,以更大的样本量评估监测他克莫司血清谷浓度的准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/881b/8301588/ff07aa7f695f/CTS-14-1303-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/881b/8301588/ff07aa7f695f/CTS-14-1303-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/881b/8301588/ff07aa7f695f/CTS-14-1303-g001.jpg

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A Low Tacrolimus Concentration/Dose Ratio Increases the Risk for the Development of Acute Calcineurin Inhibitor-Induced Nephrotoxicity.低浓度/剂量的他克莫司会增加急性钙调神经磷酸酶抑制剂诱导的肾毒性发生风险。
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Tacrolimus Pharmacokinetic and Pharmacogenomic Differences between Adults and Pediatric Solid Organ Transplant Recipients.他克莫司在成人和儿童实体器官移植受者之间的药代动力学和药物基因组学差异
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