Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Biol Blood Marrow Transplant. 2017 Dec;23(12):2184-2191. doi: 10.1016/j.bbmt.2017.08.027. Epub 2017 Aug 30.
Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). Comparisons of different ATG formulations are lacking, however. Our aim was to synthesize all published efficacy evidence to enable a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process, and the website www.ClinicalTrials.gov. In addition, a trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. We identified a total of 6 RCTs, including 2 formulations: anti-T lymphocyte globulin (ATLG; Grafalon, Neovii Biotech, Lexington, MA) and polyclonal globulin immunized with human thymocytes (Thymoglobulin [Thymo]; Genzyme-Sanofi, Cambridge, MA). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment for preventing graft-versus-host disease (GVHD) was ATLG, which had a more favorable hazard ratio (HR) compared with standard treatment (chronic GVHD: HR, .42; 95% confidence interval [CI], .31 to .56; acute GVHD grade II-IV: HR, .54; 95% CI, .39 to .73; acute GVHD grade III-IV: HR, .50; 95% CI, .29 to .86), whereas both ATLG and Thymo were at least similarly effective in terms of transplantation-related mortality (TRM) (ATLG: HR, .90; 95% CI, .61 to 1.32; Thymo: HR, .90; 95% CI, .56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS) (HR, .86; 95% CI, .59 to 1.26). Our NMA provides the first report of the relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head-to-head comparisons are available, based on the present analysis, ATLG seems to be the best option to prevent chronic and acute GVHD. Both formulations show similar efficacy in terms of TRM, whereas Thymo appears to be the better treatment option in terms of OS.
自 2000 年以来，各种 III 期随机对照试验（RCT）已经研究了兔抗胸腺细胞球蛋白（ATG）在同种异体干细胞移植（allo-SCT）后的疗效。然而，不同 ATG 制剂的比较尚缺乏。我们的目的是综合所有已发表的疗效证据，以比较 allo-SCT 中所有可用的兔 ATG 制剂。我们进行了系统的文献回顾，以确定所有可用的 III 期 RCT 证据。我们搜索了 Cochrane 图书馆、MEDLINE、MEDLINE In-Process 和 www.ClinicalTrials.gov 网站。此外，还添加了 2016 年美国血液学会年会上报告的一项试验，以纳入最新证据。我们共确定了 6 项 RCT，包括 2 种制剂：抗 T 淋巴细胞球蛋白（ATLG；Neovii Biotech，马萨诸塞州列克星敦的 Grafalon）和用人胸腺细胞免疫的多克隆球蛋白（Thymo；Genzyme-Sanofi，马萨诸塞州剑桥的 Thymoglobulin）。使用常规网络荟萃分析（NMA）综合证据。预防移植物抗宿主病（GVHD）的最佳治疗方法是 ATLG，与标准治疗相比，其具有更有利的风险比（HR）（慢性 GVHD：HR，.42；95%置信区间[CI]，.31 至.56；急性 GVHD Ⅱ-Ⅳ级：HR，.54；95%CI，.39 至.73；急性 GVHD Ⅲ-Ⅳ级：HR，.50；95%CI，.29 至.86），而 ATLG 和 Thymo 在移植相关死亡率（TRM）方面至少同样有效（ATLG：HR，.90；95%CI，.61 至 1.32；Thymo：HR，.90；95%CI，.56 至 1.44）。Thymo 在总生存（OS）方面似乎是更好的治疗选择（HR，.86；95%CI，.59 至 1.26）。我们的 NMA 首次报告了所有可用的兔 ATG 制剂在接受 allo-SCT 的患者中的相对疗效。在有来自随机头对头比较的额外数据之前，根据本分析，ATLG 似乎是预防慢性和急性 GVHD 的最佳选择。两种制剂在 TRM 方面显示出相似的疗效，而 Thymo 在 OS 方面似乎是更好的治疗选择。
