他克莫司和单次术中高剂量抗淋巴细胞球蛋白与他克莫司单药治疗成人肝移植：一项研究者驱动的随机对照试验的一年结果。

Tacrolimus and Single Intraoperative High-dose of Anti-T-lymphocyte Globulins Versus Tacrolimus Monotherapy in Adult Liver Transplantation: One-year Results of an Investigator-driven Randomized Controlled Trial.

机构信息

Starzl Abdominal Transplant Unit, University Hospitals Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

出版信息

Ann Surg. 2018 Nov;268(5):776-783. doi: 10.1097/SLA.0000000000002943.

DOI:10.1097/SLA.0000000000002943

PMID:30307410

Abstract

OBJECTIVE

The aim of the study is to evaluate whether intra-operative induction with anti-lymphocytic serum (ALS) is superior to no induction in adult liver transplantation (LT).

BACKGROUND

The efficacy of ALS induction remains inconclusive in LT, because of poorly designed trials.

METHODS

A randomized controlled trial was conducted, including 206 adults (>15 years) and comparing tacrolimus monotherapy (TAC, n = 109) and tacrolimus plus a single, intraoperative, high-dose (9 mg/kg), rabbit anti-T-lymphocyte globulins (ATLG; n = 97). All patients had similar follow-up, including Banff-scored biopsies. Rejection was considered clinically relevant and treated if pathologic and biochemical changes were concordant. The primary endpoint was immunosuppression minimization to monotherapy; secondary endpoints were biopsy-proven rejection, clinical rejection, patient (PS) and graft (GS) survival.

RESULTS

At 1 year, 79/81 (96.3%) ATLG and 101/102 (99.0%) TAC patients were steroid-free (P = 0.585); 28 (34.6%) ATLG, and 31 (30.4%) TAC patients were on double-drug immunosuppression (P = 0.633). One-year PS and GS of ATLG and TAC patients were 84% and 92% (P = 0.260) and 76% and 90% (P = 0.054).Despite significantly a fewer day-7 moderate-to-severe acute cellular rejections (ACR) in ATLG group (10.0% vs 24.0% in TAC group, P = 0.019), cumulative proportion of patients experiencing steroid-sensitive (11.3% ATLG vs 14.7% TAC, P = 0.539), steroid-resistant (2.1% ATLG vs 3.7% TAC, P = 0.686) and chronic rejection (1.0% ATLG vs 0.9% TAC, P = 1.000) were similar. ATLG administration brought about greater hemodynamic instability and blood products use (P = 0.001).

CONCLUSIONS

At 1 year from LT, ATLG induction did not significantly affect immunosuppressive load, treated rejection, patient, and graft survival. The observed adverse events justify a modification of dosing and timing of ATLG infusion. Long-term results are required to judge the ATLG possible benefits on immunosuppressive load and tolerance induction.

摘要

目的

本研究旨在评估成人肝移植术中应用抗淋巴细胞血清（ALS）诱导是否优于无诱导。

背景

由于试验设计不佳，ALS 诱导在肝移植中的疗效仍不确定。

方法

进行了一项随机对照试验，纳入 206 例（>15 岁）成人，并比较了他克莫司单药治疗（TAC，n=109）和他克莫司联合术中单次高剂量（9mg/kg）兔抗 T 淋巴细胞球蛋白（ATLG；n=97）。所有患者均接受了类似的随访，包括 Banff 评分活检。如果病理和生化改变一致，则认为排斥反应具有临床相关性并进行治疗。主要终点是免疫抑制最小化至单药治疗；次要终点是活检证实的排斥反应、临床排斥反应、患者（PS）和移植物（GS）存活率。

结果

在 1 年时，81/81（96.3%）例 ATLG 和 102/102（99.0%）例 TAC 患者均无需使用类固醇（P=0.585）；28 例（34.6%）ATLG 和 31 例（30.4%）TAC 患者接受了双重免疫抑制治疗（P=0.633）。ATLG 和 TAC 患者的 1 年 PS 和 GS 分别为 84%和 92%（P=0.260）和 76%和 90%（P=0.054）。尽管 ATLG 组第 7 天中重度急性细胞排斥反应（ACR）的发生率明显较低（10.0%比 TAC 组 24.0%，P=0.019），但经历类固醇敏感（11.3%ATLG 比 14.7%TAC，P=0.539）、类固醇耐药（2.1%ATLG 比 3.7%TAC，P=0.686）和慢性排斥反应（1.0%ATLG 比 0.9%TAC，P=1.000）的患者比例相似。ATLG 给药导致更大的血流动力学不稳定和血液制品使用（P=0.001）。