Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease
Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease
复制标题
DOI：
10.1182/blood-2012-11-465583
复制
发表时间：
2013-03-21
期刊：
影响因子：
20.3
通讯作者：
Martin, Paul J.
中科院分区：
文献类型：
--
作者：
Inamoto, Yoshihiro;Storer, Barry E.;Martin, Paul J.
本研究试图描述治疗失败的原因，确定相关的预后因素，并为试验测试研究产品或方案二线系统治疗慢性移植物抗宿主病（GVHD）的试验制定较短期的终点。研究队列（312例患者）接受慢性GVHD的二线全身治疗。主要终点是无失败生存期（FFS），定义为无三线治疗、无复发死亡率和二线治疗期间复发的恶性肿瘤。治疗改变是治疗失败的主要原因。二线治疗后6个月的FFS为56%。6个月时较低的类固醇剂量与随后停止免疫抑制治疗相关。多变量分析显示，移植时的高危疾病、二线治疗时的下消化道受累以及二线治疗时严重的NIH总体评分与治疗失败的风险增加相关。这三个因素用于定义风险组，并计算每个风险组在6个月时的成功率，无论是否有6个月时的各种类固醇剂量限制作为成功的额外标准。这些成功率可以作为临床相关的和有效的短期终点的基础，在临床研究中，评估慢性GVHD的二线全身治疗药物。
This study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD.