Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies:: Final results and long-term follow-up of an open-label prospective randomized trial
Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies:: Final results and long-term follow-up of an open-label prospective randomized trial
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DOI：
10.1182/blood.v93.10.3267.410k22_3267_3275
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发表时间：
1999-05-15
期刊：
影响因子：
20.3
通讯作者：
Schaefer, UW
中科院分区：
文献类型：
--
作者：
Beelen, DW;Elmaagacli, A;Schaefer, UW
在一项单中心开放标签前瞻性研究中，共有134例恶性血液病骨髓移植受者在移植后5周内被随机分配至使用甲硝唑和环丙沙星（n = 68）或单独使用环丙沙星（n = 66）的细菌去污药物，II至IV级急性移植物抗宿主病（GVHD）的发展被定义为主要研究终点。根据意向治疗，17名患者（25%）随机接受联合去污药物治疗，33名患者（50%）随机接受环丙沙星单药治疗，发生II级至IV级GVHD（P <0.002）。随机分配至环丙沙星单药组的患者中II级至IV级急性GVHD的发生率较高，这是由于与随机分配至联合去污药物组的患者相比，发生急性GVHD的肝脏或肠道受累的患者数量增加了两倍以上（P < .003）。研究药物对II级至IV级急性GVHD的影响仅在来自基因型HLA相同的同胞供体的移植受者（n = 80）中显著，而在来自HLA相同的同胞以外的供体的移植受者（n = 54）中，研究组之间的II级至IV级急性GVHD频率没有显著差异。联合去污与移植后5周内肠道厌氧菌培养生长的显著减少相关（P < .00001）。此外，厌氧菌生长的培养物数量（P <0.005）以及移植后厌氧菌的中位浓度（P <0.0001）在感染II至IV级急性GVHD的患者中更高。两个研究组之间的慢性GVHD和总生存率均无显著差异。在疾病早期接受治疗的HLA相同同胞供体患者中，联合去污药物治疗后的5年生存率估计值（60% +/- 11%）略高于单独使用环丙沙星（46% +/- 9%），但不显著。总之，本研究提供的证据表明，针对骨髓移植受者肠道厌氧菌的抗微生物化疗显着降低急性GVHD的严重程度，并支持肠道厌氧菌微生物群在人类骨髓移植后急性GVHD的发病机制中发挥作用的理论。(C)1999年，美国血液学会。
In a single-center open-label prospective study, a total of 134 marrow transplant recipients with hematologic malignancies were randomly assigned to a bacterial decontamination medication using metronidazole and ciprofloxacin (n = 68) or ciprofloxacin alone (n = 66) during 5 weeks posttransplant, The development of grades II to IV acute graft-versus-host disease (GVHD) was defined as the primary study endpoint. According to the intention-to-treat, 17 patients (25%) randomized to the combined decontamination medication and 33 patients (50%) randomized to ciprofloxacin alone developed grades II to IV GVHD (P < .002). The higher frequency of grades II to IV acute GVHD in patients randomized to ciprofloxacin alone resulted from a more than twofold increased number of patients developing liver or intestinal involvement with acute GVHD compared with patients randomized to the combined decontamination medication (P < .003). The influence of the study medication on grades II to IV acute GVHD was significant only in recipients of transplants from genotypically HLA-identical sibling donors (n = 80), whereas in recipients of transplants from donors other than HLA-identical siblings (n = 54), grades II to IV acute GVHD frequencies between the study arms were not significantly different. The combined decontamination was associated with a significant reduction of culture growth of intestinal anaerobic bacteria during 5 weeks posttransplant (P < .00001). In addition, the number of cultures with growth of anaerobic bacteria (P < .005) as well as the median concentrations of anaerobic bacteria in the posttransplant period (P < .0001) were higher in patients contracting grades II to IV acute GVHD. Neither chronic GVHD nor overall survival was significantly different between the two study arms, In patients with HLA-identical sibling donors who were treated in early disease stages, the 5-year survival estimate was slightly, but not significant, higher after the combined decontamination medication (60% +/- 11%) compared with ciprofloxacin alone (46% +/- 9%). In conclusion, the present study provides evidence that antimicrobial chemotherapy targeted to intestinal anaerobic bacteria in marrow transplant recipients significantly reduces the severity of acute GVHD and supports the theory that the intestinal anaerobic bacterial microflora plays a role in the pathogenesis of acute GVHD after human marrow transplantation. (C) 1999 by The American Society of Hematology.