Cross Cancer Institute, Edmonton, Alberta, Canada.
Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada.
Clin Transplant. 2022 Aug;36(8):e14732. doi: 10.1111/ctr.14732. Epub 2022 Jun 2.
Despite the common use of cyclosporine (CsA) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic stem cell transplant, the optimal CsA trough target remains unknown.
Here, we report on outcomes of adult patients following myeloablative conditioning to identify an optimal CsA trough target and characterize the most relevant timeframe post-transplant for CsA trough targeting to minimize aGVHD. We retrospectively reviewed 399 consecutive patients who underwent first peripheral blood allogeneic stem cell transplant for hematological malignancies between January 2009 and December 2018.
In the unadjusted and adjusted analyses, the incidence of grades 2-4 aGVHD was significantly higher among patients with an average CsA trough concentration <250 mcg/L compared to patients with an average CsA trough concentration ≥250 mcg/L during days 15-28 post-transplant (31.5% versus 18.8%, P = 0.037), with an odds ratio (OR) of 1.97 (95% confidence interval 1.04-3.71). In contrast, no correlations between CsA trough concentration and relapse, non-relapse mortality and overall survival was found.
In conclusion, early post-transplant CsA trough concentrations are an important factor in the prophylaxis against aGVHD. Our findings suggest that CsA trough concentrations should be maximized between days 15-28 post-myeloablative transplant.
尽管环孢素（CsA）常用于异基因干细胞移植后急性移植物抗宿主病（aGVHD）的预防，但最佳 CsA 谷浓度目标仍不清楚。
在这里，我们报告了接受清髓性预处理的成人患者的结果，以确定最佳的 CsA 谷浓度目标，并描述移植后最相关的时间窗，以便通过 CsA 谷浓度靶向最小化 aGVHD。我们回顾性分析了 2009 年 1 月至 2018 年 12 月期间接受首次外周血异基因干细胞移植治疗血液系统恶性肿瘤的 399 例连续患者。
在未调整和调整分析中，与移植后 15-28 天平均 CsA 谷浓度≥250mcg/L 的患者相比，平均 CsA 谷浓度<250mcg/L 的患者发生 2-4 级 aGVHD 的发生率显著更高（31.5%与 18.8%，P=0.037），优势比（OR）为 1.97（95%置信区间 1.04-3.71）。相比之下，CsA 谷浓度与复发、非复发死亡率和总生存率之间没有相关性。
总之，移植后早期 CsA 谷浓度是预防 aGVHD 的一个重要因素。我们的研究结果表明，CsA 谷浓度应在清髓性移植后 15-28 天内最大化。
