Brehm Niklas, Biavasco Francesca, Clausen Johannes, Jung Johannes, Maas-Bauer Kristina, Wäsch Ralph, Verbeek Mareike, Nuernbergk Christoph, Ihorst Gabriele, Seropian Stuart, Finke Jürgen, Gowda Lohith, Sidlik Muskatel Rakefet, Peffault de Latour Régis, Socie Gérard, Wehr Claudia, Michonneau David, Zeiser Robert
Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Internal Medicine I, Ordensklinikum Linz-Elisabethinen, Linz, Austria.
Bone Marrow Transplant. 2025 Apr 14. doi: 10.1038/s41409-025-02586-2.
Intestinal glucocorticoid-refractory (SR) acute (a) graft-versus-host disease (GVHD) causes high non-relapse mortality (NRM) in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Recent preclinical data indicate that acute GVHD causes a loss of intestinal neuroendocrine L-cells leading to reduced levels of glucagon-like peptide-2 (GLP-2). GLP-2 substitution improved GVHD severity and increased Paneth cells and intestinal stem cells in mice. This motivated us to treat patients with refractory intestinal aGHVD using the GLP-2-analogon teduglutide. In this retrospective multicenter survey, 17 patients received teduglutide as salvage-therapy for SR-intestinal aGVHD. The best response (CR or PR) at any time point during and after treatment was 64.7% (11/17) including 41.2% (7/17) CR and 23.5% (4/17) PR. At a median follow-up of 28 weeks after teduglutide 10/17 patients are alive. Most patients experienced an increase of the albumin serum level within 2 months after the first teduglutide dose, including patients who clinically did not respond to teduglutide treatment. No specific teduglutide-related toxicity was observed. Our retrospective analysis suggests that teduglutide is safe and has activity in a fraction of patients with intestinal SR-aGVHD, which needs validation in a prospective trial.
肠道糖皮质激素难治性（SR）急性（a）移植物抗宿主病（GVHD）在异基因造血细胞移植（allo - HCT）后的患者中导致高非复发死亡率（NRM）。最近的临床前数据表明，急性GVHD导致肠道神经内分泌L细胞丢失，导致胰高血糖素样肽 - 2（GLP - 2）水平降低。GLP - 2替代改善了GVHD的严重程度，并增加了小鼠的潘氏细胞和肠道干细胞。这促使我们使用GLP - 2类似物替度鲁肽治疗难治性肠道aGHVD患者。在这项回顾性多中心调查中，17例患者接受替度鲁肽作为SR - 肠道aGVHD的挽救治疗。治疗期间及之后任何时间点的最佳反应（CR或PR）为64.7%（11/17），包括41.2%（7/17）的CR和23.5%（4/17）的PR。在替度鲁肽治疗后中位随访28周时，17例患者中有10例存活。大多数患者在首次使用替度鲁肽剂量后2个月内血清白蛋白水平升高，包括临床上对替度鲁肽治疗无反应的患者。未观察到与替度鲁肽相关的特异性毒性。我们的回顾性分析表明，替度鲁肽是安全的，并且在一部分肠道SR - aGVHD患者中具有活性，这需要在前瞻性试验中进行验证。
