监测移植物抗宿主病预防中麦考酚酸在脐血移植中的药物浓度。
Drug monitoring for mycophenolic acid in graft-vs-host disease prophylaxis in cord blood transplantation.
机构信息
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
出版信息
Br J Clin Pharmacol. 2020 Dec;86(12):2464-2472. doi: 10.1111/bcp.14354. Epub 2020 May 30.
AIMS
We performed the retrospective analysis to clarify the significance of drug monitoring for mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), in prophylaxis for graft-vs-host disease (GVHD) in cord blood transplantation.
METHODS
We retrospectively analysed the data of 46 patients who underwent first cord blood transplantation and received GVHD prophylaxis with tacrolimus plus MMF. MPA levels were measured on days 7 and 21, and 24-hour areas under the curve (AUC ) were estimated.
RESULTS
The engraftment and 3-year overall survival rates of all patients were 94% and 78%, respectively. The cumulative incidence of sepsis before engraftment was higher in patients with AUC on day 7 of >60 μg h/mL than in other patients (33 vs 6%, P = .02). The cumulative incidence of grade II-IV acute GVHD was higher in patients with AUC on day 21 of ≤30 μg h/mL than in other patients (80 vs 50%, P = .04). The cumulative incidence of human herpesvirus 6 reactivation was higher in patients with AUC on day 21 of ≤48 μg h/mL (median) than in other patients (50 vs 19%, P = .03).
CONCLUSION
Blood level of MPA was associated with risk of acute GVHD and infection. A prospective trial evaluating the benefit of personalized MMF dosing using MPA levels is needed.
目的
我们进行了回顾性分析，以阐明霉酚酸（MPA），即吗替麦考酚酯（MMF）的活性形式，在脐血移植中预防移植物抗宿主病（GVHD）中的药物监测的意义。
方法
我们回顾性分析了 46 例接受首次脐血移植并接受他克莫司联合 MMF 预防 GVHD 的患者数据。在第 7 天和第 21 天测量 MPA 水平，并估计 24 小时 AUC。
结果
所有患者的植入和 3 年总生存率分别为 94%和 78%。在植入前，AUC 在第 7 天>60μg h/mL 的患者中，败血症的累积发生率高于其他患者（33%比 6%，P=0.02）。在 AUC 在第 21 天≤30μg h/mL 的患者中，2 级至 4 级急性 GVHD 的累积发生率高于其他患者（80%比 50%，P=0.04）。在 AUC 在第 21 天≤48μg h/mL（中位数）的患者中，人疱疹病毒 6 再激活的累积发生率高于其他患者（50%比 19%，P=0.03）。
结论
MPA 的血液水平与急性 GVHD 和感染的风险相关。需要进行前瞻性试验，评估使用 MPA 水平进行个体化 MMF 剂量的获益。
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