儿童异基因造血干细胞移植后闭塞性细支气管炎综合征研究进展

doi:10.12372/jcp.2023.22e1137

摘要/Abstract

摘要：

闭塞性细支气管炎综合征（BOS）是儿童异基因造血干细胞移植后罕见且致命的非感染性肺部并发症之一。原发性移植物功能不良、移植物抗宿主病、淋巴细胞浸润性细支气管炎、胃食管反流、空气污染等多种危险因素与儿童造血干细胞移植后BOS的发生密切相关。由于早期症状不明显、开放性肺活检风险高、病理生理改变不可逆及部分患儿激素治疗效果不理想等原因，儿童移植后BOS的临床诊疗十分具有挑战性。文章综述儿童异基因造血干细胞移植后BOS的流行病学特点、发病机制、诊断方法及治疗进展，为进一步完善适用于儿童移植后BOS的诊疗规范提供建议。

关键词: 闭塞性细支气管炎综合征, 造血干细胞移植, 儿童

Abstract:

Bronchiolitis obliterans syndrome (BOS) is one of the rare and fatal non-infectious pulmonary complications after allogeneic haematopoietic stem cell transplantation (HSCT) in children. Mutiple risk factors such as primary graft dysfunction, graft-versus-host disease (GVHD), lymphocytic bronchiolitis, gastro-oesophageal reflux, and air pollution, particularly in children, have been reported to be the most common contributions to the bronchiolitis obliterans syndromepost-HSCT. An early diagnosis and treatment of BOS following HSCT is challenging due to the lack of obvious early symptoms, high risk of open lung biopsy, irreversible pathophysiological changes, and the failure of steroid treatment in some children. In this review, we summarize research advances in the epidemiology, pathogenesis, diagnosis, and treatment of this lethal noninfectious pulmonary complication, and provide suggestions for further improvement of diagnostic and therapeutic norms applicable to post-HSCT BOS in children.

Key words: bronchiolitis obliterans syndrome, haematopoietic stem cell transplantation, child

习必鑫, 胡群, 刘爱国. 儿童异基因造血干细胞移植后闭塞性细支气管炎综合征研究进展[J]. 临床儿科杂志, 2023, 41(8): 629-633.

XI Bixin, HU Qun, LIU Aiguo. Research advances of the bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplant in children[J]. Journal of Clinical Pediatrics, 2023, 41(8): 629-633.

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疾病分级	轻度	轻度	中度	重度
疾病评分	0分	1分	2分	3分
临床症状	无症状	爬楼梯后气促	平地步行后气促	休息时气促，需要氧气吸入支持
肺功能	FEV1≥80%	60%<FEV1<80%	40%<FEV1<60%	FEV1<40%

鉴别要点	BOS	IPS	COP	ILD
危险因素	白消安、HLA错配、 GVHD、脐血移植	清髓性预处理、TBI、 GVHD、急性白血病	女性供者、HLA错配、 GVHD、外周血干细胞移植	外周血干细胞移植（75%）、 GVHD (70%)
发病时间	移植后+100天~ +2年	移植后+21天~ +120天	移植后+2月~ +15月	移植后+11.3月以内
临床症状	气促、咳嗽、喘息、劳力性呼吸困难	咳嗽、呼吸困难、低氧血症、呼吸衰竭	发热、乏力、干咳少痰、活动后气促、呼吸困难	渐进性劳力性气促、干咳、杵状指、呼吸衰竭
肺功能	阻塞性通气功能障碍	限制性通气功能障碍	限制性通气功能障碍	限制性通气功能障碍
胸部CT	马赛克征、支气管扩张、小气道壁增厚	多肺叶浸润影	斑片状实变影、磨玻璃影、结节状实变影	弥漫性浸润影、蜂窝肺
病理特点	大量淋巴细胞浸润、细支气管壁纤维化	弥漫性肺泡受损、急性渗出性病变	肺泡上皮受损、肺泡腔内肉芽组织增生	弥漫性肺间质纤维化
治疗及预后	激素/CAS/FK506+FAM 终末期肺移植，预后差	激素冲击/TNF-α抑制剂终末期肺移植，预后差	激素0.5~1mg·kg^-1·d^-1,慢减，预后良好，但易复发	激素，预后差、2年内死亡率39%