Iron overload in myelodysplastic syndromes (MDS)
Iron overload in myelodysplastic syndromes (MDS)
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DOI：
10.1007/s12185-017-2367-1
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发表时间：
2018-01-01
影响因子：
2.1
通讯作者：
Gattermann, Norbert
中科院分区：
文献类型：
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作者：
Gattermann, Norbert
铁过载（IOL）开始在MDS患者中发展之前，他们成为输血依赖性，因为无效的红细胞生成抑制铁调素在肝脏中的生产，从而导致不受限制的肠铁摄取。然而，MDS中铁超负荷的最重要原因是长期输血治疗。虽然输血依赖性本身是一个反映骨髓功能不良的不良预后因素，但随后的输血铁超负荷对低风险MDS患者的生存率有额外的剂量依赖性负面影响。心功能不全似乎是重要的，在这种情况下，作为慢性贫血，年龄相关的心脏合并症，和铁超载的后果。另一个潜在的问题是铁相关的内皮功能障碍。有证据表明，随着年龄的增长，高循环铁水平恶化动脉粥样硬化表型。通过对间充质基质细胞以及造血细胞（特别是红系前体细胞）的不利影响，输血IOL似乎也会加重MDS中的骨髓衰竭。患者系列和临床试验表明，铁螯合剂去铁胺和地拉罗司可以改善少数输血依赖患者的造血功能。对登记数据的分析表明，铁螯合治疗为MDS患者提供了生存益处，但仍然缺乏前瞻性随机临床试验的数据。
Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.