Summary Generalised severe recessive dystrophic epidermolysis bullosa (RDEB‐GS) is a rare, incurable genetic disorder in which an essential skin component, type 7 collagen (C7), is defective or missing. As a result, skin and mucous membranes detach from the body, causing blisters and wounds. Bone marrow transplantation (BMT) can restore C7 in the skin, probably by supplying mesenchymal stem cells (MSCs) which turn into healthy new skin cells. However, BMT is a risky and unpleasant procedure because the drugs needed to stop the patient's immune system rejecting the donated bone marrow can themselves cause illness and sometimes death. Immune cells in the transplanted tissue may even attack the patient, causing graft versus host disease (GvHD). These doctors at the University of Minnesota tried a different BMT protocol in 10 children with RDEB‐GS, using less intense immune‐suppression pre‐transplant. Three days post‐transplant they gave an immunosuppressive drug called cyclophosphamide (PTCy). Two months later, when the patient's body had accepted the donor tissue, they were able to give more MSCs from the same donor. The graft failed in three patients, two of whom underwent repeat BMT followed in one by severe complications and death a year later. Successfully transplanted patients tended to show more C7 in their skin biopsies and improved symptoms with reductions in itch, pain and areas of blistered skin. None suffered GvHD in the short term. The authors conclude that PTCy BMT is feasible in people with RDEB‐GS, even with “less‐than‐perfectly‐matched” donors, and allows repeat “top‐up” MSC grafts from the same donor.
Summary 泛发型重度隐性营养不良性大疱性表皮松解症 (RDEB‐GS) 是一种罕见的不可治愈的遗传疾病,此疾病患者皮肤的主要成分 7 型胶原 (C7) 出现缺陷或缺失。 由此导致皮肤和粘膜与身体脱离,引发水疱和伤口。骨髓移植 (BMT) 可恢复皮肤中的 C7,其机理很可能是提供可转变为健康新皮肤细胞的间充质干细胞 (MSC)。但是,BMT 是一种存在风险的不适操作,因为需要用药来阻止患者免疫系统排斥捐献的骨髓,而这些药物本身可能导致疾病,有时甚至致死。移植组织中的免疫细胞甚至可能攻击患者,导致移植物抗宿主疾病 (GvHD)。 这些明尼苏达州立大学的医生们在 10 名 RDEB‐GS 儿童中尝试了一种不同的 BMT 方案,该方案使用较低强度的移植前免疫抑制。移植后 3 天,向他们给用称为环磷酰胺 (PTCy) 的免疫抑制药物。2 个月后,当患者身体已经接受供体组织时,他们可以从相同供体接受更多 MSC。 此移植在 3 名患者中失败,其中 2 名经历了重复的 BMT,1 名发生了严重并发症,并在 1 年后死亡。移植成功患者在皮肤活检中显示了 C7 增多和症状改善以及瘙痒、疼痛和水疱皮肤面积减少的趋势。短期无人发生 GvHD。 作者们得出结论,PTCy BMT 在 RDEB‐GS 患者中是可行的,甚至使用“不很完美匹配”的供体时也是如此,且允许通过相同供体重复“额外”MSC 移植。
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