Meiser B M, Uberfuhr P, Fuchs A, Schulze C, Nollert G, Mair H, Martin S, Pfeiffer M, Reichenspurner H, Kreuzer E, Reichart B
Department of Cardiac Surgery, University of Munich, Grosshadern Medical Center, Germany.
J Heart Lung Transplant. 1997 Aug;16(8):795-800.
Acute myocardial rejection refractory to treatment still contributes significantly to patient death after intrathoracic transplantation. A historical series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having persistent rejection unresponsive to treatment at the time of conversion. Mean periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1-year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus treatment groups, with most of the deaths in the OKT3 group occurring early (p = 0.064). Causes of death for patients receiving OKT3 included acute rejection (n = 5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the result of infections. Eighty percent of patients treated with OKT3 subsequently experienced further rejection episodes, in many cases necessitating methotrexate therapy. In contrast, only one patient (7.1%) from the tacrolimus group was diagnosed with rejection after conversion (p < 0.001). In conclusion, when compared with OKT3 therapy, a switch in baseline immunosuppression from cyclosporine to tacrolimus seems to be markedly more effective, as well as being safe for the treatment of persistent acute rejection.
治疗难治的急性心肌排斥反应仍是胸腔内移植术后患者死亡的重要原因。将一组接受OKT3(5毫克/天,共10天)治疗的25例患者的历史数据,与我们目前使用他克莫司(0.1毫克/千克/天,目标全血浓度为13至18纳克/毫升)治疗的14例患者的经验进行比较:所有39例患者在转换治疗时均存在持续的治疗无反应性排斥反应。平均随访时间分别为842.9天和342.6天。OKT3治疗组和他克莫司治疗组的1年患者精算生存率分别为64.0%和76.2%,OKT3组的大多数死亡发生在早期(p = 0.064)。接受OKT3治疗的患者死亡原因包括急性排斥反应(n = 5)、感染(n = 3)、癌症(n = 2)、多器官功能衰竭(n = 1)和移植血管疾病(n = 1)。他克莫司治疗组的两例死亡是感染所致。接受OKT3治疗的患者中有80%随后经历了进一步的排斥反应发作,在许多情况下需要甲氨蝶呤治疗。相比之下,他克莫司组只有1例患者(7.1%)在转换治疗后被诊断为排斥反应(p < 0.001)。总之,与OKT3治疗相比,将基线免疫抑制从环孢素转换为他克莫司似乎明显更有效,而且对治疗持续性急性排斥反应是安全的。