McDiarmid S V, Busuttil R W, Ascher N L, Burdick J, D'Alessandro A M, Esquivel C, Kalayoglu M, Klein A S, Marsh J W, Miller C M
University of California, Los Angeles.
Transplantation. 1995 Feb 27;59(4):530-6.
We report on the efficacy and safety of FK506 (tacrolimus) compared with a cyclosporine (CsA)-based immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients (< 12 years) participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABO-compatible liver transplant. Intravenous FK506 was initiated at 0.1 mg/kg per day, followed by oral FK506 beginning at 0.3 mg/kg per day. The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. The CsA group was treated according to each center's usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsy-proven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of follow-up 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80% and graft survival 70% in the FK506 group compared with 81% and 71% respectively, in the CsA group. 48% of the FK506 group remained rejection-free compared with 21% of the CsA group, and 79% of FK506-treated patients did not require OKT3 compared with 68% of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major toxicities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30% incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.
我们报告了参与美国一项多中心随机试验的小儿肝移植受者（<12岁）接受1年治疗后，与基于环孢素（CsA）的免疫抑制方案相比，FK506（他克莫司）的疗效和安全性。在首次ABO血型相容肝移植后，患者接受FK506或CsA作为主要免疫抑制治疗。静脉注射FK506起始剂量为每天0.1mg/kg，随后口服FK506起始剂量为每天0.3mg/kg。调整剂量以维持血浆谷浓度在0.5 - 2.0ng/ml。CsA组根据各中心的常规方案进行治疗。两组均接受相同初始剂量的皮质类固醇。所有排斥反应均经活检证实，并采用标准化算法治疗排斥反应。30例患者随机分为FK506组，20例分为CsA组。随访12个月后，FK506组有20例患者，CsA组有13例患者。FK506组患者生存率为80%，移植物生存率为70%，而CsA组分别为81%和71%。FK506组48%的患者无排斥反应，而CsA组为21%；FK506治疗的患者中79%不需要使用OKT3，而CsA治疗的患者为68%。在第一年的每个时间点，FK506组的累积皮质类固醇剂量都较少。两组严重和轻微感染的发生率相似。报告的主要毒性反应为肾毒性、神经毒性和胃肠道紊乱。两组之间差异未达到统计学意义，尽管FK506组更常报告严重神经系统事件、腹泻和消化不良。两组12个月时的平均血清肌酐无差异。FK506组平均血清胆固醇有降低趋势。FK506组未出现多毛症，而CsA组发生率为30%。总之，与CsA相比，FK506治疗的小儿移植受者排斥反应有减少趋势，而两种药物的副作用谱相似。
