Ganschow Rainer, Schulz Tania, Meyer Thomas, Broering Dieter C, Burdelski Martin
Departments of Pediatrics, University of Hamburg, Germany.
J Pediatr Gastroenterol Nutr. 2004 Feb;38(2):198-203. doi: 10.1097/00005176-200402000-00018.
In pediatric solid organ transplantation, the Epstein-Barr virus (EBV)-related lymphoproliferative disorders (PTLD) still play a major role in post-transplant morbidity and mortality. The aim of the study was to determine the incidence of PTLD in pediatric patients with liver transplant who receive low-dose immunosuppression protocols.
All pediatric patients (n = 269) received a dual immunosuppression therapy consisting of cyclosporine A (initial trough levels, 170-200 microg/L; trough levels for maintenance immunosuppression after 1 year, 80-100 microg/L) and prednisolone (starting dose, 60 mg/m2). Steroids were reduced to 30 mg/m2 after 1 week, followed by a weekly tapering to 5 mg/m2. Seventy-seven of 269 patients were switched to tacrolimus therapy. The authors evaluated the significance of EBV-DNA monitoring by quantitative polymerase chain reaction in identifying patients at risk for PTLD.
Patient survival was 90.3%; graft survival was 85.9%. Eight patients lost their grafts because of chronic rejection. The incidence of PTLD was low (0.7%), although a significant EBV viral load was found in 42.4% of the patients. One third of the patients with a viral load of 3,000 genomes/10(5) cells or greater had clinical signs of EBV infection.
The authors conclude that low-dose immunosuppressive protocols significantly reduce the incidence of PTLD. In patients treated with that regimen, the monitoring of EBV viral load seems not to be helpful. It can be assumed that low-dose immunosuppression does not suppress EBV-specific cytotoxic CD8+ T cells, thus allowing the host to control EBV infection without the risk of PTLD. Our low-dose immunosuppression protocol did not increase the risk of chronic rejection.
在小儿实体器官移植中，爱泼斯坦-巴尔病毒（EBV）相关的淋巴增殖性疾病（PTLD）在移植后发病率和死亡率方面仍起主要作用。本研究的目的是确定接受低剂量免疫抑制方案的小儿肝移植患者中PTLD的发生率。
所有小儿患者（n = 269）接受了由环孢素A（初始谷浓度，170 - 200μg/L；1年后维持免疫抑制的谷浓度，80 - 100μg/L）和泼尼松龙（起始剂量，60mg/m²）组成的双重免疫抑制治疗。1周后将类固醇剂量减至30mg/m²，随后每周逐渐减量至5mg/m²。269例患者中有77例改用他克莫司治疗。作者评估了通过定量聚合酶链反应监测EBV-DNA在识别PTLD风险患者中的意义。
患者生存率为90.3%；移植物生存率为85.9%。8例患者因慢性排斥反应失去移植物。PTLD的发生率较低（0.7%），尽管42.4%的患者发现有显著的EBV病毒载量。病毒载量为3000个基因组/10⁵细胞或更高的患者中有三分之一有EBV感染的临床体征。
作者得出结论，低剂量免疫抑制方案显著降低了PTLD的发生率。在用该方案治疗的患者中，监测EBV病毒载量似乎并无帮助。可以推测，低剂量免疫抑制不会抑制EBV特异性细胞毒性CD8⁺T细胞，从而使宿主能够控制EBV感染而无PTLD风险。我们的低剂量免疫抑制方案未增加慢性排斥反应的风险。
