Penack Olaf, Marchetti Monia, Ruutu Tapani, Aljurf Mahmoud, Bacigalupo Andrea, Bonifazi Francesca, Ciceri Fabio, Cornelissen Jan, Malladi Ram, Duarte Rafael F, Giebel Sebastian, Greinix Hildegard, Holler Ernst, Lawitschka Anita, Mielke Stephan, Mohty Mohamad, Arat Mutlu, Nagler Arnon, Passweg Jakob, Schoemans Hélène, Socié Gerard, Solano Carlos, Vrhovac Radovan, Zeiser Robert, Kröger Nicolaus, Basak Grzegorz W
Medical Clinic, Department for Haematology, Oncology and Tumorimmunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Division of Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
Lancet Haematol. 2020 Feb;7(2):e157-e167. doi: 10.1016/S2352-3026(19)30256-X.
Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.
移植物抗宿主病（GVHD）是异基因干细胞移植后导致死亡和发病的主要因素。由于精心设计的大规模临床研究结果数量较少，全球范围内GVHD的预防和治疗存在很大差异。2014年，为了规范治疗方法，欧洲血液和骨髓移植学会发布了关于血液系统恶性肿瘤成年患者中，在人类白细胞抗原（HLA）匹配的同胞或无关供体移植情况下GVHD管理的建议。在此，我们更新这些建议，包括2014年之后发表的研究结果。证据搜索分三步进行：首先，广泛扫描已发表的试验、荟萃分析和系统评价；其次，经过几轮辩论后，针对特定问题加入专家意见；第三，进行精确搜索以针对有争议或快速更新的问题。基于这些证据和2014年的建议，欧洲血液和骨髓移植学会移植并发症工作组成员中的五人就GVHD预防、药物管理以及急性和慢性GVHD的治疗制定了38条声明。随后，他们通过招募20名具有GVHD管理专业知识的专家，创建了欧洲血液和骨髓移植学会GVHD管理建议专家小组。采用基于电子邮件的两轮德尔菲专家小组方法来达成共识。将修改后的美国国立综合癌症网络证据和共识类别应用于批准的声明。我们对29条建议达成了100%的共识，对9条建议达成了95%的共识。这些建议的关键更新包括更广泛地使用兔抗T细胞球蛋白；对于仅有皮肤或上消化道表现的2级急性GVHD，采用更低剂量的类固醇进行管理；对于闭塞性细支气管炎综合征应使用氟替卡松、阿奇霉素和孟鲁司特；以及为对类固醇难治的急性和慢性GVHD增加新的治疗选择。此外，我们讨论了单倍体相合移植和儿科患者情况下GVHD预防和管理的具体方面，但本综述未提供关于这些程序的正式建议。欧洲血液和骨髓移植学会建议将这些建议作为干细胞移植期间GVHD常规管理的基础。
