Calcineurin activity as a functional index of immunosuppression after allogeneic stem-cell transplantation
Calcineurin activity as a functional index of immunosuppression after allogeneic stem-cell transplantation
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DOI：
10.1097/01.tp.0000114612.55925.22
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发表时间：
2004-03-27
期刊：
影响因子：
6.2
通讯作者：
Cordonnier, C
中科院分区：
文献类型：
--
作者：
Sanquer, S;Schwarzinger, M;Cordonnier, C
背景作者先前已经表明，来自耐药慢性移植物抗宿主病（GVHD）患者的单核细胞表达高钙调神经磷酸酶（CN）活性，这表明CN活性的体外评估可能是一个有用的指标，以估计环孢素A（CsA）提供的免疫抑制程度。本研究的目的是评估异基因干细胞移植（SCT）后前2个月内CN活性，并将其演变与急性GVHD的发生相关联。在21个月期间入组了31名同种异体SCT受者。所有患者均接受CsA（2 mg/kg/天）和甲氨蝶呤（第1、3和6天）预防GVHD。在移植前测量CN活性，然后每周一次，至少2个月。18例患者在中位时间22.5天发生急性11级或更高GVHD，并接受类固醇治疗。CN活性显着增加，在这18例患者相比，13例患者谁没有发展GVHD。受试者工作特征曲线分析表明，以28 pmol RII/mg蛋白/min CN活性作为临界值，急性11级或更高级别GVHD的敏感性为89%，特异性为54%。CN活性似乎是一个有前途的治疗试验，以预测急性移植物抗宿主病后异基因SCT。CsA体内疗效的功能评估为CsA剂量调整提供了新的见解，特别是，给予其最有效的剂量，而不是目前所采用的最大耐受剂量。
Background. The authors have previously shown that mononuclear cells derived from patients with resistant chronic graft-versus-host-disease (GVHD) express high calcineurin (CN) activity, suggesting that in vitro assessment of CN activity may be a useful index to estimate the degree of immunosuppression afforded by cyclosporine A (CsA). The goal of this study was to assess CN activity during the first 2 months after allogeneic stem-cell transplantation (SCT) and to correlate its evolution with the occurrence of acute GVHD.Methods. Thirty-one allogeneic SCT recipients were enrolled during a 21-month period. All received GVHD prophylaxis with CsA (2 mg/kg/day) and methotrexate (on days 1, 3, and 6). CN activity was measured before transplant, and then once weekly, for at least 2 months.Results. Eighteen patients developed acute grade 11 or higher GVHD at a median time of 22.5 days and were treated with steroids. CN activity was significantly increased in these 18 patients when compared with 13 patients who did not develop GVHD. Analysis involving the receiver operating characteristic curve demonstrated that acute grade 11 or higher GVHD can be predicted with a sensitivity of 89% and a specificity of 54% with the use of a cutoff value of 28 pmol RII/mg proteins/min of CN activity.Conclusions. CN activity appears to be a promising therapeutic test to predict acute GVHD after allogeneic SCT. This functional assessment of the in vivo efficacy of CsA opens new insights for CsA dose adjustment-in particular, the administration of its most efficient dose instead of its maximal tolerated dose, as is currently performed.