Sanquer S, Schwarzinger M, Maury S, Yakouben K, Rafi H, Pautas C, Kuentz M, Barouki R, Cordonnier C
Service de Biochimie B, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Transplantation. 2004 Mar 27;77(6):854-8. doi: 10.1097/01.tp.0000114612.55925.22.
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.
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.
Eighteen patients developed acute grade II 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 II 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.
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.
作者先前已表明，来自耐药性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，这表明体外评估CN活性可能是估计环孢素A（CsA）免疫抑制程度的有用指标。本研究的目的是评估异基因干细胞移植（SCT）后前2个月内的CN活性，并将其变化与急性GVHD的发生相关联。
在21个月期间招募了31名异基因SCT受者。所有人均接受了CsA（2mg/kg/天）和甲氨蝶呤（在第1、3和6天）预防GVHD。在移植前测量CN活性，然后至少2个月每周测量一次。
18名患者在中位时间22.5天出现急性II级或更高等级的GVHD，并接受了类固醇治疗。与13名未发生GVHD的患者相比，这18名患者的CN活性显著增加。涉及受试者工作特征曲线的分析表明，使用CN活性截断值28pmol RII/mg蛋白/分钟，可预测急性II级或更高等级的GVHD，敏感性为89%，特异性为54%。
CN活性似乎是预测异基因SCT后急性GVHD的一种有前景的治疗测试。这种对CsA体内疗效的功能评估为CsA剂量调整开辟了新的思路——特别是给予其最有效剂量而非目前所采用的最大耐受剂量。
