Wang Yafeng, Liu Dandan, Gao Haili, Liu Wei, Mao Yanna
Department of Hematology and Oncology, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China.
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China.
Sci Rep. 2025 Mar 20;15(1):9606. doi: 10.1038/s41598-025-92979-6.
Very early onset inflammatory bowel disease (VEO-IBD) with interleukin-10 receptor-A (IL-10RA) defects is characterised by severe and unmanageable intestinal inflammation, perianal lesions, and a high mortality rate, with the onset of the disease occurring at a very early age. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective treatments for VEO-IBD patients with IL-10 signaling deficiency. The objective of this study was to evaluate the clinical effectiveness of allo-HSCT in the treatment of children with VEO-IBD and IL-10RA deficiency, and to provide further clinical insights. A retrospective analysis and summary of the clinical data of seven patients with VEO-IBD and IL-10RA deficiency from January 2021 to December 2023 was performed. These patients subsequently underwent allo-HSCT after receiving a reduced-intensity conditioning regimen followed by a cyclosporine-based regimen for the prevention of graft versus host disease (GVHD). Hematopoietic reconstruction was performed on seven children with VEO-IBD combined with IL-10RA deficiency. Four patients developed grade I-II GVHD, while three patients developed grade III-IV GVHD after undergoing allo-HSCT. At a median follow-up of 518 days after allo-HSCT (range: 210-1072 days), six patients were alive, while one patient died 16 months after the procedure because of chronic GVHD and severe infections. The 3-year cumulative overall survival (OS) probability rate was 80.0% (95% CI: 44.7-100.0). All VEO-IBD patients demonstrated weight gain following HSCT, with substantial improvements observed in severe malnutrition and growth retardation associated with IL-10RA deficiency post-transplantation. Allo-HSCT is thus identified as the optimal curative therapy for VEO-IBD patients with IL10-RA deficiency. The importance of early multidisciplinary intervention and co-management of VEO-IBD is paramount in improving HSCT outcomes.
伴有白细胞介素-10受体A(IL-10RA)缺陷的极早发型炎症性肠病(VEO-IBD)的特征是肠道炎症严重且难以控制、肛周病变以及高死亡率,疾病在极早期发病。目前,异基因造血干细胞移植(allo-HSCT)是治疗伴有IL-10信号缺陷的VEO-IBD患者最有效的治疗方法之一。本研究的目的是评估allo-HSCT治疗VEO-IBD且伴有IL-10RA缺陷儿童的临床疗效,并提供进一步的临床见解。对2021年1月至2023年12月期间7例VEO-IBD且伴有IL-10RA缺陷患者的临床资料进行回顾性分析和总结。这些患者在接受减低强度预处理方案后接受基于环孢素的方案预防移植物抗宿主病(GVHD),随后进行allo-HSCT。对7例VEO-IBD合并IL-10RA缺陷的儿童进行了造血重建。4例患者发生I-II级GVHD,3例患者在接受allo-HSCT后发生III-IV级GVHD。allo-HSCT后中位随访518天(范围:210-1072天),6例患者存活,1例患者在术后16个月因慢性GVHD和严重感染死亡。3年累计总生存率(OS)概率为80.0%(95%CI:44.7-100.0)。所有VEO-IBD患者在HSCT后体重增加,移植后与IL-10RA缺陷相关的严重营养不良和生长发育迟缓有显著改善。因此,allo-HSCT被确定为伴有IL10-RA缺陷的VEO-IBD患者的最佳治愈性疗法。VEO-IBD早期多学科干预和联合管理对于改善HSCT结局至关重要。