Chand D H, Southerland S M, Cunningham R J
Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Pediatr Transplant. 2001 Feb;5(1):32-6. doi: 10.1034/j.1399-3046.2001.00025.x.
The aim of this study was to evaluate the efficacy and side-effects of tacrolimus in pediatric transplant patients previously receiving cyclosporin A (CsA). This study was a retrospective chart review strengthened by a concomitant patient interview. Eleven pediatric cardiac or renal transplant patients, who had been converted from CsA to tacrolimus from October 1995 to January 1999 at The Cleveland Clinic Foundation, were included; there were six renal and five cardiac transplant patients. Each chart was reviewed to assess transplanted organ function pre- and post-conversion. For the six renal transplant patients, creatinine levels and biopsy findings were evaluated. For the five cardiac transplant patients, cardiac catheterization and routine biopsy data were analyzed likewise. Epstein Barr virus (EBV) status was also evaluated in each patient. In addition, each parent or patient was interviewed to ascertain dates of transplant, current medications, and side-effects. The patients' ages ranged from 6 to 20 yr (mean age 14.6 yr). All patients had been converted to tacrolimus. Eight patients were converted for treatment of refractory rejection, two were converted because of CsA-associated side-effects, and one patient was converted empirically for a history of multiple previous transplant rejections. Seven out of eight patients who received tacrolimus for rejection therapy improved. One patient had complete resolution of gingival hyperplasia. Another patient who previously developed hemolytic uremic syndrome on CsA had no further evidence of hemolysis. Four patients were weaned off steroid therapy. Despite conversion, two renal transplant patients progressed to chronic rejection. Five patients exhibited no side-effects. Side-effects experienced included transient hyperglycemia in conjunction with steroid use, headaches, and tremors that subsided rapidly. Four of 11 patients developed post-transplant lymphoproliferative disease (PTLD). Fortunately, reducing the dose of tacrolimus and/or surgical resection of the mass (if present), eradicated the disease. In conclusion, conversion therapy successfully provides an alternate treatment for acute rejection. It also enabled some patients to discontinue steroid therapy, maximizing growth potential. PTLD is a severe, potentially life-threatening complication that needs to be recognized and monitored closely. In conclusion, tacrolimus has been shown to be a very effective agent for the treatment of refractory organ rejection, but must be used cautiously.
本研究的目的是评估他克莫司对先前接受环孢素A（CsA）治疗的儿科移植患者的疗效和副作用。本研究是一项回顾性病历审查，并辅以同步的患者访谈。纳入了11例儿科心脏或肾脏移植患者，他们于1995年10月至1999年1月在克利夫兰诊所基金会从CsA转换为他克莫司；其中有6例肾移植患者和5例心脏移植患者。审查每份病历以评估转换前后移植器官的功能。对于6例肾移植患者，评估了肌酐水平和活检结果。对于5例心脏移植患者，同样分析了心导管检查和常规活检数据。还评估了每位患者的爱泼斯坦-巴尔病毒（EBV）状态。此外，对每位家长或患者进行访谈，以确定移植日期、当前用药情况和副作用。患者年龄在6至20岁之间（平均年龄14.6岁）。所有患者均已转换为他克莫司治疗。8例患者因难治性排斥反应而转换治疗，2例因CsA相关副作用而转换，1例因既往多次移植排斥史而经验性转换。接受他克莫司治疗排斥反应的8例患者中有7例病情改善。1例患者的牙龈增生完全消退。另1例先前在CsA治疗期间发生溶血性尿毒症综合征的患者，不再有溶血的证据。4例患者停用了类固醇治疗。尽管进行了转换，2例肾移植患者仍进展为慢性排斥反应。5例患者未出现副作用。出现的副作用包括与使用类固醇相关的短暂高血糖、头痛和迅速消退的震颤。11例患者中有4例发生了移植后淋巴细胞增生性疾病（PTLD）。幸运的是，减少他克莫司剂量和/或手术切除肿块（如果存在）消除了该疾病。总之，转换治疗成功地为急性排斥反应提供了替代治疗。它还使一些患者能够停用类固醇治疗，最大限度地发挥生长潜力。PTLD是一种严重的、可能危及生命的并发症，需要得到识别并密切监测。总之，已证明他克莫司是治疗难治性器官排斥反应的非常有效的药物，但必须谨慎使用。
