Treatment of inherited bone marrow failure syndromes beyond transplantation
Treatment of inherited bone marrow failure syndromes beyond transplantation
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DOI：
10.1182/asheducation-2017.1.96
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发表时间：
2017-12-01
影响因子：
3
通讯作者：
Cle, Diego V.
中科院分区：
文献类型：
--
作者：
Calado, Rodrigo T.;Cle, Diego V.
尽管通过添加替代造血干细胞来源在移植方面取得了重大进展，但许多遗传性骨髓衰竭综合征患者仍然不适合移植。此外，测序小组的可用性已显著提高了诊断，通过确定隐遗传病例。雄激素是治疗先天性角化不良和范可尼贫血患者骨髓衰竭的主要非移植疗法，在高达80%的病例中达到应答。丹那唑和羟甲氧酮更常用，但男性化和肝毒性是主要的不良事件。Diamond-Blackfan贫血通常用皮质类固醇治疗，但大多数患者最终对这种治疗变得难治性，毒性有限。生长因子在遗传性病例中仍有作用，特别是在先天性中性粒细胞减少症中粒细胞集落刺激因子。新的治疗方法是必要的，血小板生成素受体激动剂、亮氨酸、槲皮素和新的基因治疗方法可能在未来对遗传性病例有益。
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists leucine quercetin and novel gene therapy approaches may benefit inherited cases in the future.