儿童异基因造血干细胞移植相关性肠道血栓性微血管病变临床特征分析

Clinical characteristics of intestinal thrombotic microangiopathosis associated with allogeneic hematopoietic stem cell transplantation in children

目的 探讨儿童异基因造血干细胞移植(allo-HSCT)相关性肠道血栓性微血管病变(iTMA)的临床病理学特征和治疗方案,为其早期诊断和治疗提供参考。方法 回顾性分析3例allo-HSCT后考虑存在iTMA患儿的临床资料。结果 3例患儿在allo-HSCT后20~50天出现腹痛、顽固性腹泻或严重便血等消化道症状;胃镜检查均发现不同程度的黏膜出血,结肠镜显示活动性或陈旧性出血,黏膜质脆,部分可见糜烂;病理检查均显示不同程度固有层消失,腺体不典型增生或缺失,可见微血栓形成,其中1例可见巨细胞病毒包涵体。结合临床症状考虑患儿存在iTMA。2例患儿减停钙调磷酸酶体抑制剂及对症处理后症状于2周左右缓解,其中1例患儿停钙调磷酸酶体抑制剂,加用麦考酚酯联合甲基泼尼松龙、血浆置换及去纤苷治疗20余天后临床症状逐渐好转。结论 iTMA可为儿童allo-HSCT后并发症,可与移植物抗宿主病(GVHD)、巨细胞病毒感染伴随存在。对于allo-HSCT后出现严重难治性腹泻患儿应尽早通过消化道内镜及活检病理检查进行iTMA和GVHD及巨细胞病毒感染的鉴别诊断,以助临床及时修正治疗策略。

Objective To explore the clinicopathological features and treatment of intestinal thrombotic microangiopathopathy(iTMA) associated with allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children,and to provide reference for the early diagnosis and treatment of iTMA. Methods The clinical data of 3 children with iTMA after allo-HSCT treatment were retrospectively analyzed. Results All three patients developed gastrointestinal symptoms such as abdominal pain, intractable diarrhea or severe hematochezia 20 to 50 days after allo-HSCT. Gastroscopy showed different degrees of mucosal bleeding. Colonoscopy showed active or old bleeding, brittle mucous membrane and some erosion.Pathological examination revealed different degrees of mucosal lamina propria disappearance, atypical hyperplasia or absence of glands, and microthrombosis. Virus inclusion bodies were seen in 1 child. Combined with clinical symptoms, iTMA was considered in all the children. After the withdrawal of calcineurin inhibitor and symptomatic treatment, the symptoms of 2 children were relieved in about 2 weeks. After 20 days of stopping the use of calcineurin inhibitors and adding mycophenolate combined with methylprednisolone, plasma exchange, and deinoside, the clinical symptoms of one patient gradually improved.Conclusions iTMA is a complication of allo-HSCT in children and may be associated with graft-versus-host disease(GVHD)and cytomegalovirus infection. For children with severe refractory diarrhea after allo-HSCT, the differential diagnosis of iTMA,GVHD and cytomegalovirus infection should be made by gastrointestinal endoscopy and biopsy pathology as soon as possible,so as to help clinical timely modification of treatment strategies.