Hashmi Shahrukh, Ahmed Mohammad, Murad M Hassan, Litzow Mark R, Adams Roberta H, Ball Lynne M, Prasad Vinod K, Kebriaei Partow, Ringden Olle
Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Internal Medicine, Providence Hospital, Washington, DC, USA.
Lancet Haematol. 2016 Jan;3(1):e45-52. doi: 10.1016/S2352-3026(15)00224-0. Epub 2015 Nov 27.
Graft-versus-host disease (GVHD) is the major limitation of allogeneic haemopoietic stem-cell transplantation (HSCT), for which no approved treatments are available. Use of mesenchymal stromal cells (MSCs) has become standard practice in some European countries, but controversy exists for their benefit. The aim of this meta-analysis was to analyse available evidence for the benefit of MSC treatments in steroid-resistant acute GVHD.
We did a systematic review and meta-analysis to assess response to and survival after MSC treatment in patients with steroid-refractory acute GVHD. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which MSCs were administered to patients with steroid-refractory acute GVHD. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was survival at 6 months from the first infusion of MSCs.
We identified 628 citations with our search, of which 610 were excluded after review and a further five did not contain pertinent data. Thus, our meta-analysis included 13 non-randomised studies at moderate risk of bias, comprising a total of 336 patients. Six studies provided data for the primary outcome analysis (119 patients). Survival at 6 months after MSC treatment was 63% (95% CI 50-74; I(2)=41%). Survival did not differ with respect to age, MSC culture medium, or dose of MSCs delivered.
Available evidence suggests that infusion of MSCs could be an acceptable treatment for patients with steroid-refractory acute GVHD. Randomised clinical trials are needed urgently to assess different treatment modalities for steroid-refractory acute GVHD.
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移植物抗宿主病（GVHD）是异基因造血干细胞移植（HSCT）的主要限制因素，目前尚无获批的治疗方法。在一些欧洲国家，使用间充质基质细胞（MSC）已成为标准治疗方法，但对于其益处仍存在争议。本荟萃分析的目的是分析关于MSC治疗对类固醇难治性急性GVHD有益的现有证据。
我们进行了一项系统评价和荟萃分析，以评估MSC治疗对类固醇难治性急性GVHD患者的反应和生存率。我们在MEDLINE、Embase、Ovid和Cochrane Central数据库中搜索已发表的研究，并使用ClinicalTrials.gov和其他网站查找未发表的研究和会议摘要。我们纳入了将MSC给予类固醇难治性急性GVHD患者的前瞻性和回顾性研究。两名研究人员根据严格的选择标准独立提取数据。由于预期存在异质性，因此使用随机效应模型汇总各研究的结果。我们的主要结局是首次输注MSC后6个月的生存率。
我们通过搜索识别出628篇文献，其中610篇在审查后被排除，另有5篇不包含相关数据。因此，我们的荟萃分析纳入了13项偏倚风险为中度的非随机研究，共336例患者。6项研究提供了主要结局分析的数据（119例患者）。MSC治疗后6个月的生存率为63%（95%CI 50-74；I²=41%）。生存率在年龄、MSC培养基或输注的MSC剂量方面没有差异。
现有证据表明，输注MSC可能是类固醇难治性急性GVHD患者可接受的治疗方法。迫切需要进行随机临床试验，以评估类固醇难治性急性GVHD的不同治疗方式。
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