Schweiger M, Wasler A, Prenner G, Tripolt M, Schwarz M, Tscheliessnigg K H
Department for Transplantation, Medical University Graz, University of Surgery, Graz, Austria.
Transplant Proc. 2005 Dec;37(10):4528-31. doi: 10.1016/j.transproceed.2005.11.053.
Late acute cellular rejection is associated with decreased survival and the development of CAV. Among new immunosuppressive drugs introduced into clinical practice, everolimus, has been shown to be safe in cardiac transplantation. We report our experience with everolimus in heart transplant recipients who developed late acute cellular cardiac rejection.
Patients with a history of previous rejection episodes who experienced cardiac rejection were switched to an everolimus, cyclosporine, and steroid immunosuppressive regimen. All patients had already received statins and antihypertensive medications. Everolimus, cyclosporine trough levels, and laboratory values were controlled monthly. Drug administration was adapted to an everolimus trough level between 3 and 8 ng/mL, mean maintenance dosage was 0.25 to 1.5 mg twice a day. Death, safety, side effects, biopsy-proven acute rejection episodes, laboratory values, and blood levels were evaluated retrospectively.
Four cardiac allograft recipients (two male, two female), at a median of 1473.25 days post-orthotopic heart transplantation (oHTx) (range = 65 to 3045), received 1 to 1.5 mg everolimus per day. Over a follow-up period of at least 2 month (range = 2 to 10) the mortality was 0%. The drug was well tolerated; no acute cellular rejection greater than grade 1a (ISHLT grading) was observed after 2 months. In one patient increased cholesterol values and in two others, elevated triglyceride levels were seen, but were controlled with increased statin therapy. No obvious increased creatinine values were seen with everolimus.
In conclusion, conversion to an everolimus-based immunosuppressive regimen after late cardiac rejection is safe and effective; no major side effects were observed.
晚期急性细胞排斥反应与生存率降低及冠状动脉血管病变（CAV）的发生有关。在引入临床实践的新型免疫抑制药物中，依维莫司已被证明在心脏移植中是安全的。我们报告了我们在发生晚期急性细胞性心脏排斥反应的心脏移植受者中使用依维莫司的经验。
有既往排斥反应史且发生心脏排斥反应的患者改用依维莫司、环孢素和类固醇免疫抑制方案。所有患者均已接受他汀类药物和抗高血压药物治疗。每月监测依维莫司、环孢素谷浓度及实验室指标。药物给药根据依维莫司谷浓度在3至8 ng/mL之间进行调整，平均维持剂量为每天0.25至1.5 mg，分两次服用。对死亡、安全性、副作用、活检证实的急性排斥反应发作、实验室指标和血药浓度进行回顾性评估。
4例心脏移植受者（2例男性，2例女性），原位心脏移植（oHTx）后中位时间为1473.25天（范围为65至3045天），每天接受1至1.5 mg依维莫司治疗。在至少2个月（范围为2至10个月）的随访期内，死亡率为0%。该药物耐受性良好；2个月后未观察到大于1a级（国际心脏和肺移植学会分级）的急性细胞排斥反应。1例患者胆固醇值升高，另外2例患者甘油三酯水平升高，但通过增加他汀类药物治疗得到控制。使用依维莫司未观察到明显的肌酐值升高。
总之，晚期心脏排斥反应后改用基于依维莫司的免疫抑制方案是安全有效的；未观察到重大副作用。
