Department of Bone Marrow Transplantation, West-German Cancer Center, University Hospital Essen, Hufelandstrasse, 55 45122, Essen, Germany.
Department of Pediatric Stem Cell Transplantation, Center of Pediatrics III, University Hospital Essen, Essen, Germany.
Ann Hematol. 2019 Oct;98(10):2407-2419. doi: 10.1007/s00277-019-03754-3. Epub 2019 Jul 23.
Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.
类固醇难治性急性移植物抗宿主病（GVHD）与重要的发病率和死亡率相关。虽然高剂量类固醇是 GVHD 的既定一线治疗方法，但一般不接受二线治疗。在对 65 例连续的严重、类固醇难治性、肠道 GVHD 患者（92%为 4 期）的分析中，与常规 GVHD 治疗相比，额外的回肠造口术显著降低了总死亡率（危险比 0.54；95%置信区间，0.36-0.81；p=0.003）。回肠造口术组的中位总生存期为 16 个月，而常规治疗组为 4 个月。在回肠造口术组中，感染性和 GVHD 相关死亡率均降低（40%比 77%）。手术后粪便量显著减少（p=0.001），表明回肠造口后肠道适应。相关研究表明，回肠造口术诱导免疫调节，激活 T 细胞减少>50%（p=0.04），调节性 T 细胞增加。患者肠道微生物群的观察到的改变也可能有助于回肠造口的治疗效果。这些数据表明，回肠造口术在类固醇难治性 GVHD 患者中引起了显著的临床反应，同时减少了促炎免疫细胞和肠道微生物群的改变。回肠造口术是治疗类固醇难治性急性胃肠道 GVHD 的一种治疗选择，需要在前瞻性临床试验中进一步验证。
