Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation
Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation
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DOI：
10.1038/bmt.2008.85
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发表时间：
2008-07-01
影响因子：
4.8
通讯作者：
Bornhaeuser, M.
中科院分区：
文献类型：
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作者：
Haentzschel, I.;Freiberg-Richter, J.;Bornhaeuser, M.
由于在异基因 SCT 受者中测得霉酚酸 MPA) 的低谷水平，我们根据浓度 AUC) 水平下的 MPA 面积进行了一项针对吗替麦考酚酯 MMF) 剂量的初步研究。 29 名患者是从匹配的兄弟姐妹（n = 7）和无关的捐赠者（n = 22）移植的。从第-1天起口服他克莫司以达到5-10ng/ml的血药浓度谷值。 MMF 从第 0 天开始，每日两次静脉注射 1500 毫克。计划在移植后第 3、7 和 11 天通过 HPLC 测量 MPA 的 AUC。修改MMF剂量以实现35-60μg/ml/h的MPA AUC。分别调整后，第 7 天和第 11 天分别有 66% 和 75% 超过了较低的 AUC 目标。 III-IV级急性GVHD的累积发生率为28%8/29)。 24 名可评估患者中的 8 名（33%）患有有限的 n 3) 或广泛的 n 5) 慢性 GVHD。总体而言，本研究的结果表明，移植后早期以 MPA 暴露为目标是可行的。在未来的试验中，基于 MPA C(max) 或 C(2h) 水平的简化 MMF 靶向策略似乎是有必要的，该试验涉及更多患者，在门诊环境中稍后的时间点进行。
As low trough levels of mycophenolic acid MPA) have been measured in recipients of allo-SCTs, we performed a pilot study targeting mycophenolate mofetil MMF) doses according to the MPA area under the concentration AUC) levels. Twenty-nine patients were transplanted from matched sibling n = 7) and unrelated donors n = 22). Tacrolimus was given orally from day -1 to achieve trough blood levels of 5 - 10 ng/ml. MMF was started on day 0 at 1500 mg intravenously b.i.d. AUC measurements of MPA by HPLC were scheduled on days 3, 7 and 11 after transplantation. The MMF dose was modified to achieve an MPA AUC of 35 - 60 mu g/ml/h. With the respective adjustments 66 and 75% surpassed the lower AUC target on days 7 and 11, respectively. The cumulative incidence of grade III-IV acute GVHD was 28% 8/29). Eight out of 24 evaluable patients 33%) suffer from limited n 3) or extensive n 5) chronic GVHD. Overall, the results of this study suggest that targeting of MPA exposure is feasible early after transplantation. A simplified MMF targeting strategy based on MPA C(max) or C(2h) levels seems to be warranted in future trials involving more patients at later time points in the outpatient setting.