Teduglutide for treatment-refractory severe intestinal acute graft-versus-host disease - a multicenter survey.

IF 4.5 2区医学 Q1 HEMATOLOGY

Bone Marrow Transplantation Pub Date : 2025-04-14 DOI:10.1038/s41409-025-02586-2

Niklas Brehm, Francesca Biavasco, Johannes Clausen, Johannes Jung, Kristina Maas-Bauer, Ralph Wäsch, Mareike Verbeek, Christoph Nuernbergk, Gabriele Ihorst, Stuart Seropian, Jürgen Finke, Lohith Gowda, Rakefet Sidlik Muskatel, Régis Peffault de Latour, Gérard Socie, Claudia Wehr, David Michonneau, Robert Zeiser

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引用次数: 0

Abstract

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.

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特杜葡肽治疗难治性严重肠道急性移植物抗宿主病-一项多中心调查。

肠道糖皮质激素难治性（SR）急性(a)移植物抗宿主病（GVHD）导致同种异体造血细胞移植（alloo - hct）后患者的高非复发死亡率（NRM）。最近的临床前数据表明，急性GVHD引起肠道神经内分泌l细胞的损失，导致胰高血糖素样肽-2 （GLP-2）水平降低。GLP-2替代改善了小鼠GVHD的严重程度，增加了Paneth细胞和肠道干细胞。这促使我们使用glp -2类似物teduglutide治疗难治性肠道aGHVD患者。在这项回顾性多中心调查中，17例患者接受了特杜葡肽作为sr -肠aGVHD的抢救治疗。在治疗期间和治疗后的任何时间点，最佳缓解（CR或PR）为64.7%(11/17)，其中CR为41.2% (7/17)，PR为23.5%（4/17）。在teduglutide 10/17患者存活后的中位随访时间为28周。大多数患者在第一次给药后2个月内出现血清白蛋白水平升高，包括临床对特杜葡肽治疗无反应的患者。未观察到特杜卢肽相关的特异性毒性。我们的回顾性分析表明，teduglutide是安全的，并且在一小部分肠道SR-aGVHD患者中具有活性，这需要在前瞻性试验中进行验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bone Marrow Transplantation 医学-免疫学

CiteScore

8.40

自引率

8.30%

发文量

337

审稿时长

6 months

期刊介绍： Bone Marrow Transplantation publishes high quality, peer reviewed original research that addresses all aspects of basic biology and clinical use of haemopoietic stem cell transplantation. The broad scope of the journal thus encompasses topics such as stem cell biology, e.g., kinetics and cytokine control, transplantation immunology e.g., HLA and matching techniques, translational research, and clinical results of specific transplant protocols. Bone Marrow Transplantation publishes 24 issues a year.