Ernst Jana, Reinsch Steffen, Mentzel Hans-Joachim, Milde Till, Gruhn Bernd
Department of Pediatric and Adolescent Medicine, Jena University Hospital, Jena, Germany.
Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany.
Ann Hematol. 2025 Jul 15. doi: 10.1007/s00277-025-06491-y.
Acute graft-versus-host disease (aGVHD) as complication after allogeneic hematopoetic stem cell transplantation (allo-HSCT) occurs in up to 70% of patients. The survival prognosis depends on the severity of GVHD and response to first-line therapy. In patients who are refractory to both, steroids and ruxolitinib, an unmet medical need exists, especially in severe gastrointestinal forms of aGVHD. We report the case of a 12-year-old male patient who developed severe gastrointestinal aGVHD after allo-HSCT for the treatment of high-risk acute myeloid leukemia. The grade IV aGVHD of the intestine showed no improvement under triple immunosuppression with corticosteroids, cyclosporine A and ruxolitinib. After receiving four weekly infusions of human allogeneic mesenchymal stromal cells DRK-BaWü-He-FFM (MSC-FFM), intestinal inflammation finally improved, as reflected by ameliorated symptoms, normalized intestinal wall thickness (ultrasonography) and decreasing calprotectin levels. Intestinal mucosal healing was further supported by a strict, formula-based modular diet. The present case supports efficacy and safety of MSC-FFM in combination with modular nutrition in complicated courses of aGVHD of the intestine refractory to multiple lines of therapy and introduces intestinal wall thickness and calprotectin levels as valuable markers of disease activity.
急性移植物抗宿主病(aGVHD)作为异基因造血干细胞移植(allo-HSCT)后的并发症,在高达70%的患者中出现。生存预后取决于移植物抗宿主病的严重程度及对一线治疗的反应。对于对类固醇和鲁索替尼均难治的患者,存在未满足的医疗需求,尤其是在严重胃肠道型aGVHD患者中。我们报告了一名12岁男性患者的病例,该患者在接受allo-HSCT治疗高危急性髓系白血病后发生了严重胃肠道aGVHD。在使用皮质类固醇、环孢素A和鲁索替尼进行三联免疫抑制治疗下,肠道IV级aGVHD并无改善。在接受了四周一次的人同种异体间充质基质细胞DRK-BaWü-He-FFM(MSC-FFM)输注后,肠道炎症最终得到改善,这体现在症状改善、肠壁厚度正常化(超声检查)和钙卫蛋白水平降低。严格的、基于配方的模块化饮食进一步促进了肠黏膜愈合。本病例支持了MSC-FFM联合模块化营养在多线治疗难治的肠道aGVHD复杂病程中的有效性和安全性,并引入肠壁厚度和钙卫蛋白水平作为疾病活动的重要标志物。