Centre Hospitalier et Universitaire (CHU) de Nantes, Service d'Hématologie Clinique, Nantes, France.
Biol Blood Marrow Transplant. 2010 Jan;16(1):28-34. doi: 10.1016/j.bbmt.2009.08.010. Epub 2009 Oct 1.
This single-center retrospective study analyzed 85 consecutive patients who underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess whether there is a correlation between exposure to cyclosporine-A (CsA; as measured by CsA concentrations during the first month after allo-SCT) and the risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD). The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo-SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and 247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in 36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI], 14%-32%). In univariate analysis, patients receiving allo-SCT from an HLA-matched unrelated donor had a higher risk of grade III-IV aGVHD, and patients having the lowest CsA concentration in the first and second weeks after allo-SCT had a significantly higher risk of grade III-IV aGVHD. In a multivariate logistic regression analysis, a higher CsA concentration measured during the first week following graft infusion was the strongest parameter significantly associated with a reduced risk of severe grade II-IV aGVHD (P = .012; relative risk [RR] = 0.24; 95% CI, 0.08-0.73). Of note, when adjusted by donor type, CsA concentration in week 1 remained significantly associated with risk of severe grade II-IV aGVHD (P = .014). We conclude that precise monitoring of CsA concentrations and adjustment of CsA dose early after allo-SCT may be effective to prevent onset of severe aGVHD.
本单中心回顾性研究分析了 85 例连续接受异基因造血干细胞移植（allo-SCT）的患者，旨在评估环孢素 A（CsA；根据 allo-SCT 后第一个月的 CsA 浓度测量）暴露与发生严重 III-IV 级急性移植物抗宿主病（aGVHD）的风险之间是否存在相关性。allo-SCT 后 1、2、3 和 4 周时，血液中 CsA 的中位数浓度分别为 348（范围：172-733）、284（范围：137-535）、274（范围：107-649）和 247（范围：37-695）ng/mL。总体而言，在 allo-SCT 后中位 29（范围：6-100）天，36 例（42%）患者发生 II-IV 级 aGVHD。III-IV 级 aGVHD（n = 20）的发生率为 23%（95%置信区间 [CI]，14%-32%）。在单变量分析中，接受 HLA 匹配无关供体 allo-SCT 的患者发生 III-IV 级 aGVHD 的风险更高，allo-SCT 后第一和第二周 CsA 浓度最低的患者发生 III-IV 级 aGVHD 的风险显著更高。在多变量逻辑回归分析中，输注移植物后第一周测量的较高 CsA 浓度是与严重 II-IV 级 aGVHD 风险降低显著相关的最强参数（P =.012；相对风险 [RR] = 0.24；95%CI，0.08-0.73）。值得注意的是，当按供体类型调整时，第 1 周的 CsA 浓度与严重 II-IV 级 aGVHD 的风险仍显著相关（P =.014）。我们得出结论，精确监测 allo-SCT 后早期的 CsA 浓度并调整 CsA 剂量可能有助于预防严重 aGVHD 的发生。
