Beelen D W, Haralambie E, Brandt H, Linzenmeier G, Müller K D, Quabeck K, Sayer H G, Graeven U, Mahmoud H K, Schaefer U W
Department of Bone Marrow Transplantation, University Hospital of Essen, Germany.
Blood. 1992 Nov 15;80(10):2668-76.
The influence of intestinal bacterial decontamination on the occurrence of grades II to IV acute graft-versus-host disease (GVHD) was retrospectively analyzed in 194 predominantly adult patients treated by genotypically identical sibling marrow transplantation under conditions of strict protective isolation and intestinal antimicrobial decontamination. Forty-five patients (23%) developed acute GVHD and univariate analysis identified four features that significantly increased the risk for this reaction: chronic myeloid leukemia as the underlying disease, as compared with all other disease categories (P < .0001); female marrow donors for male recipients, as compared with other gender combinations (P < .005); ineffective, as compared with sustained growth suppression of intestinal anaerobic bacteria (P < .006); and methotrexate as the sole immunoprophylactic compound, as compared with cyclosporine containing regimens (P < .05). Using the duration of anaerobic growth suppression as a time-dependent explanatory variable, proportional hazards regression analysis confirmed these features as independent predictors for acute GVHD with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to 2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3 to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to 2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1 to 1.6) for the donor/recipient gender combination (P < .008), respectively. Best subset selection modeling also identified the quality of anaerobic decontamination as the third most important predictor for acute GVHD, when all four significant features were included. Estimates of acute GVHD stratified by the quality of anaerobic bacterial growth suppression showed a strong influence of anaerobic decontamination in patients burdened by at least one of the other unfavorable factors (P < .009). In conclusion, this study provides strong evidence that sustained growth suppression of intestinal anaerobic bacteria after clinical sibling marrow transplantation can independently modulate the occurrence of grades II to IV acute GVHD, which is in concordance with previous results from animal transplantation models. Antimicrobial chemotherapy specifically targeted to the intestinal anaerobic bacterial microflora may be complementarily useful in preventing acute GVHD and should be investigated in a prospective trial.
对194例主要为成年患者进行回顾性分析，这些患者在严格的保护性隔离和肠道抗菌净化条件下接受了基因型相同的同胞骨髓移植，研究肠道细菌净化对II至IV级急性移植物抗宿主病（GVHD）发生的影响。45例患者（23%）发生了急性GVHD，单因素分析确定了四个显著增加这种反应风险的特征：与所有其他疾病类别相比，潜在疾病为慢性粒细胞白血病（P <.0001）；与其他性别组合相比，男性受者的女性骨髓供者（P <.005）；与肠道厌氧菌持续生长抑制相比无效（P <.006）；与含环孢素的方案相比，甲氨蝶呤作为唯一的免疫预防化合物（P <.05）。以厌氧菌生长抑制持续时间作为时间依赖性解释变量，比例风险回归分析证实这些特征是急性GVHD的独立预测因素，免疫预防方案的相对风险估计为1.9（95%置信区间[CI]，1.3至2.7）（P <.0004），潜在疾病为1.8（95%CI，1.3至2.5）（P <.0005），厌氧菌净化为1.7（95%CI，1.2至2.5）（P <.002），供者/受者性别组合为1.3（95%CI，1.1至1.6）（P <.008）。当纳入所有四个显著特征时，最佳子集选择模型也确定厌氧菌净化质量是急性GVHD的第三重要预测因素。按厌氧菌生长抑制质量分层的急性GVHD估计显示，在至少有一个其他不利因素的患者中，厌氧菌净化有强烈影响（P <.009）。总之，本研究提供了强有力的证据，表明临床同胞骨髓移植后肠道厌氧菌的持续生长抑制可独立调节II至IV级急性GVHD的发生，这与先前动物移植模型的结果一致。专门针对肠道厌氧细菌微生物群的抗菌化疗可能在预防急性GVHD方面具有补充作用，应在前瞻性试验中进行研究。
