异基因造血干细胞移植在溶酶体贮积症治疗中的应用

doi:10.12372/jcp.2022.22e1691

摘要/Abstract

摘要：

溶酶体贮积症（LSD）是因溶酶体的结构或功能异常导致水解酶缺陷，引起相应底物不能降解，进而导致多器官、多系统功能异常。该疾病种类多样，临床表现复杂且缺乏特异性，总体预后较差。目前治疗可采用方法有酶替代治疗、基因治疗及异基因造血干细胞移植（allo-HSCT）等。异基因造血干细胞移植是当前治疗部分儿童LSD的有效方式，尤其是非亲缘脐血干细胞（UCBT），被认为是治疗LSD的优先移植物来源。移植时年龄越小，受益程度越大，因此强调明确诊断尽早移植，建议在明显症状出现前进行。国内大多采用清髓性预处理方案。

关键词: 溶酶体贮积症, 异基因造血干细胞移植, 脐血干细胞, 儿童

Abstract:

Lysosomal storage disorders (LSD) are caused by structural or functional abnormalities of lysosomes resulting in defective hydrolases, causing failure to degrade the corresponding substrates, which leads to abnormal multi-organ and multi-system function. There are a variety of LSD, the clinical manifestations are not characteristic and overall prognosis are poor. The current available treatment methods include enzyme replacement therapy, gene therapy and allogeneic hematopoietic stem cell transplantation. Allo-HSCT is currently an effective modality for the treatment of pediatric patients with LSD, especially unrelated cord blood, which is the optimal graft source for the treatment of LSD. The younger the age of transplantation, the greater the benefit. Therefore, early transplantation at a definite diagnosis is emphasized and recommend before the onset of obvious symptoms. Most of the domestic institution choose the myeloablative conditioning as the conditioning regimen.

Key words: lysosomal storage disorders, allogeneic hematopoietic stem cell transplantation, cord blood stem cell, child

方拥军, 魏宇婷, 薛瑶. 异基因造血干细胞移植在溶酶体贮积症治疗中的应用[J]. 临床儿科杂志, 2023, 41(3): 181-186.

FANG Yongjun, WEI Yuting, XUE Yao. Advance in lysosomal storage disorders treated with allogeneic hematopoietic stem cell transplantation[J]. Journal of Clinical Pediatrics, 2023, 41(3): 181-186.

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LSD	药物治疗方案	allo-HSCT
LSD	药物治疗方案	适应证	移植时机	供体选择	预处理方案	潜在不良事件
黏多糖贮积症	ERT、基因治疗、药物伴侣、减少底物	绝对适应证：年龄<2.5岁的MPSI重型（MPS IH）患者相对适应证：年龄>2.5岁的MPS IH型患者，MPS Ⅰ非重型、MPS Ⅱ、Ⅳ、Ⅵ、Ⅶ型患者	尽早移植，移植年龄小于2周岁为佳	首选非携带、同胞全相供者，次选非亲缘脐血	清髓性方案（BuCy，联合或不联合ATG）	植入失败、移植相关并发症，无法改善移植前形成的病变，对合并神经受损患者疗效欠佳
戈谢病	ERT、基因治疗、药物伴侣、减少底物	Ⅰ型儿童期发病者为最佳适应证，对于Ⅱ型和Ⅲ型患者，建议在神经症状出现前行HSCT	尽早移植，明显肝功和神经受损等症状出现前	首选非携带、同胞全相供者，次选非亲缘脐血	清髓性方案（BuCy，联合或不联合ATG）	GVHD、感染、植入失败或死亡等移植后相关并发症
尼曼-匹克病	ERT、基因治疗、减少底物	无绝对适应证，无神经系统受损或早期症状者可考虑行HSCT	尽早移植，建议未出现神经系统改变前行HSCT	首选无携带、HLA全相合同供者，次选优非亲缘脐血	清髓性方案（BuCy，联合或不联合ATG）	疗效个体差异性大，风险较大，改善神经系统受损症状的效果及预后不确定
异染性脑白质营养不良	ERT、基因治疗	部分无症状晚婴型、轻微早期症状的青少年或成人型MLD	早期移植，建议症状发生前进行	首选未携带变异、HLA全相合同供者，次优选非亲缘脐血	清髓性方案（BuCy，联合或不联合ATG）	移植相关病死率较高，无法改善周围神经系统受累