Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
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DOI：
10.1038/leu.2012.135
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发表时间：
2012-12-01
期刊：
影响因子：
11.4
通讯作者：
Mohty, M.
中科院分区：
文献类型：
--
作者：
Baron, F.;Labopin, M.;Mohty, M.
本报告调查了1859例急性髓系白血病患者在接受低强度预处理（RIC allo-SCT）后接受异基因外周血干细胞移植后，移植物抗宿主病（GVHD）对移植结局的影响。I级急性GVHD与较低的复发风险（风险比（HR）0.7，P = 0.02）相关，转化为更好的总生存率（OS; HR 1.3; P = 0.07）的趋势。II级急性GVHD对OS没有净影响，而III-IV级急性GVHD与更差的OS相关（HR 0.4，P < 0.0.001），因为非复发死亡风险高（NRM; HR 5.2，P < 0.0001）。在时间依赖性多变量考克斯分析中，有限的慢性GVHD倾向于与较低的复发风险相关（HR 0.72; P = 0.07）转化为更好的OS（HR 1.8; P < 0.001），而广泛的慢性GVHD与较低的复发风险相关（HR 0.65; P = 0.02），但NRM也较高（人力资源3.5; P < 0.001），因此对OS没有净影响。用抗胸腺细胞球蛋白（ATG）或阿仑单抗进行的体内T细胞耗竭在预防广泛的慢性GVHD方面是成功的（P < 0.001），但ATG未改善OS，Alemtuzumab甚至使OS恶化（HR 0.65; P = 0.001）。这些结果强调了免疫介导的移植物抗白血病效应在RIC allo-SCT环境中的作用，但也需要改善严重GVHD的预防和治疗。白血病（2012）26，2462-2468; doi：10.1038/leu.2012.135
This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) 0.7, P = 0.02) translating into a trend for better overall survival (OS; HR 1.3; P = 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR 0.4, P < 0.0.001) owing to high risk of nonrelapse mortality (NRM; HR 5.2, P < 0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR 0.72; P = 0.07) translating into a better OS (HR 1.8; P < 0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR 0.65; P = 0.02) but also with higher NRM (HR 3.5; P < 0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P < 0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR 0.65; P = 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. Leukemia (2012) 26, 2462-2468; doi: 10.1038/leu.2012.135