Franke Georg-Nikolaus, Kubasch Anne Sophie, Cross Michael, Vucinic Vladan, Platzbecker Uwe
University of Leipzig Medical Center, Medical Department I - Hematology and Cell Therapy, Hemostaseology, Germany.
University of Leipzig Medical Center, Medical Department I - Hematology and Cell Therapy, Hemostaseology, Germany.
Mol Aspects Med. 2020 Oct;75:100868. doi: 10.1016/j.mam.2020.100868. Epub 2020 Jul 1.
Systemic iron overload (SIO) is a common challenge in patients with hematological diseases and develops as a result of ineffective erythropoiesis, multiple red blood cell (RBC) transfusions and disease-specific therapies. Iron homeostasis is tightly regulated as there is no physiological pathway to excrete iron from the body. Excess iron is, therefore, stored in tissues like liver, heart and bone marrow and can lead to progressive organ damage. The presence of free iron in the form of non-transferrin bound iron (NTBI) is especially detrimental. Reactive oxygen species can also cause stromal damage in the bone marrow and promote leukemic cell growth in vitro. In acute leukemias and myelodysplastic syndromes outcome is worse in patients with SIO compared to patients without. Especially in patients undergoing allogeneic HSCT presence of NTBI before or during transplant has been shown to negatively affect non-relapse mortality and overall survival. Although the mechanisms, of how these effects are mediated by SIO are not very well understood monitoring of iron status by serum markers and imaging techniques is, therefore, mandatory especially in these patients. Whether peri-interventional iron chelation may improve outcome of these patients is part of current clinical research.
全身铁过载(SIO)是血液系统疾病患者常见的挑战,其发生是无效红细胞生成、多次红细胞(RBC)输血及疾病特异性治疗的结果。由于人体没有排泄铁的生理途径,铁稳态受到严格调控。因此,过量的铁储存在肝脏、心脏和骨髓等组织中,可导致进行性器官损害。以非转铁蛋白结合铁(NTBI)形式存在的游离铁尤其有害。活性氧还可导致骨髓基质损伤,并在体外促进白血病细胞生长。与无SIO的患者相比,急性白血病和骨髓增生异常综合征患者出现SIO时预后更差。特别是在接受异基因造血干细胞移植的患者中,移植前或移植期间NTBI的存在已被证明会对非复发死亡率和总生存率产生负面影响。尽管SIO如何介导这些影响的机制尚不完全清楚,但因此,尤其是在这些患者中,通过血清标志物和成像技术监测铁状态是必不可少的。围介入期铁螯合是否可改善这些患者的预后是当前临床研究的一部分。