Porubsky M, Gruessner A C, Rana A, Jie T, Gruessner R W G
Department of Surgery, Division of Abdominal Transplantation, University of Arizona Medical Center, Tucson, Arizona.
Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.
Transplant Proc. 2014 Jul-Aug;46(6):1932-5. doi: 10.1016/j.transproceed.2014.06.010.
Pancreas transplant alone (PTA) has evolved into a viable treatment option for nonuremic patients with labile diabetes mellitus. Historically, PTA outcomes were inferior to simultaneous pancreas-kidney transplant outcomes, because of the higher rate of graft loss due to rejection in PTA recipients. But with advances in immunosuppression, PTA outcomes have improved significantly--except in young PTA recipients. The more potent immune system in young recipients appears to play a key role. In this study, our objective was to investigate outcomes of PTA, by recipient age, with the use of different immunosuppressive maintenance regimens.
Using information from the International Pancreas Transplant Registry and from the United Network for Organ Sharing, we analyzed outcomes of 393 technically successful enteric-drained transplants in the PTA category that were performed from January 2003 through December 2012. All PTA recipients underwent induction immunosuppression with thymoglobulin and pulse steroids and were then maintained on long-term low-dose prednisone. Excluded from our study group were patients who experienced surgical graft loss. We divided the 393 recipients into 2 age groups: <42 years (187 patients) versus ≥42 years (206 patients). For both the younger group and the older group, we compared 2 maintenance immunosuppressive regimens: (1) tacrolimus (Tac) and mycophenolate mofetil (MMF) versus (2) Tac/MMF and sirolimus (Srl). We refer to immunosuppression with Tac and MMF as the non-Srl regimen.
The overall 3-year graft survival rate, across both age groups, was significantly better with the Srl regimen (P = .03). Regardless of the immunosuppressive regimen used, outcomes were significantly better in the older group than in the younger group (P = .05). In the older group, with both regimens, outcomes were similar (P = .55). But in the younger group, outcomes with the Srl regimen were significantly better (P = .009) than with the non-Srl regimen and, in fact, were similar to outcomes in the older group.
Our study shows that adding Srl to the standard maintenance immunosuppressive regimen of Tac and MMF provides the best outcomes in young PTA recipients, the most immunologically robust and therefore the most immunologically challenging age group. To achieve excellent outcomes, more potent immunosuppression is required in this cohort. We think that PTA should be offered to young patients with labile diabetes before secondary complications develop.
单纯胰腺移植(PTA)已发展成为不稳定型糖尿病非尿毒症患者的一种可行治疗选择。从历史上看,PTA的治疗效果不如同期胰腺-肾脏联合移植,这是因为PTA受者中因排斥反应导致移植物丢失的发生率更高。但随着免疫抑制技术的进步,PTA的治疗效果有了显著改善——年轻的PTA受者除外。年轻受者中更强的免疫系统似乎起到了关键作用。在本研究中,我们的目的是通过使用不同的免疫抑制维持方案,按受者年龄调查PTA的治疗效果。
利用国际胰腺移植登记处和器官共享联合网络的信息,我们分析了2003年1月至2012年12月期间在PTA类别中进行的393例技术成功的肠内引流移植的治疗效果。所有PTA受者均接受了抗胸腺细胞球蛋白和冲击性类固醇诱导免疫抑制,然后长期接受低剂量泼尼松维持治疗。我们的研究组排除了手术导致移植物丢失的患者。我们将393名受者分为两个年龄组:<42岁(187例患者)和≥42岁(206例患者)。对于较年轻组和较年长组,我们比较了两种维持免疫抑制方案:(1)他克莫司(Tac)和霉酚酸酯(MMF)与(2)Tac/MMF和西罗莫司(Srl)。我们将使用Tac和MMF的免疫抑制称为非Srl方案。
在两个年龄组中,使用Srl方案的总体3年移植物存活率显著更高(P = 0.03)。无论使用何种免疫抑制方案,较年长组的治疗效果均显著优于较年轻组(P = 0.05)。在较年长组中,两种方案的治疗效果相似(P = 0.55)。但在较年轻组中,Srl方案的治疗效果显著优于非Srl方案(P = 0.009),实际上与较年长组的治疗效果相似。
我们的研究表明,在Tac和MMF的标准维持免疫抑制方案中添加Srl可使年轻PTA受者获得最佳治疗效果,这一年龄组免疫功能最强,因此也是免疫方面最具挑战性的年龄组。为了取得优异的治疗效果,该队列需要更强效的免疫抑制。我们认为,应在继发性并发症出现之前为患有不稳定型糖尿病的年轻患者提供PTA治疗。