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Iron Toxicity and Hemopoietic Cell Transplantation: Time to Change the Paradigm

机译:铁毒性和造血细胞移植:改变范例的时间

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摘要

The issue of iron overload in hemopoietic cell transplantation has been first discussed in the field of transplantation for thalassemia. Thalassemia major is characterized by ineffective erythropoiesis and hemolysis leading to severe anemia. Patients require regular blood transfusion therefore they develop iron overload causing organ damage and hematopoietic cell transplantation (HCT) is a consolidated reliably curative option.In this category of patients an important issue for transplant outcome is the iron burden before transplant and in the long-life post-transplant. Nevertheless today the concept of the impact of iron overload / toxicity on the outcome of HCT has been extended to other diseases characterized by periods of variable duration of transfusion dependence.Recent preclinical data has shown how increased production of reactive oxygen species (ROS) resulting under iron overload condition, could impair the stem cells clonality capacity, proliferation and maturation. Also, microenvironment cells could be affected through this mechanism. For this reason, iron overload is becoming an important issue also in the engraftment period post-transplant.The aim of this review is to update consolidated knowledge about the role of iron overload/iron toxicity in the HCT setting in non-malignant and in malignant diseases introducing the concept of exposition of free toxic iron forms and related cellular damage in the different stage of transplant.
机译:在地中海贫血的移植领域首先讨论了造血细胞移植中铁超载的问题。重型地中海贫血的特征在于无效的红细胞生成和溶血导致严重的贫血。患者需要定期输血,因此他们会产生铁超负荷而导致器官损伤,造血细胞移植(HCT)是可靠的综合治疗方法。在这类患者中,移植结局的重要问题是移植前和长寿命的铁负荷移植后。然而今天,铁超载/毒性对HCT结局的影响的概念已扩展到其他以输血依赖期持续时间为特征的疾病。最新的临床前数据表明,在这种情况下,如何增加活性氧的产生铁过载的情况下,可能会损害干细胞的克隆能力,增殖和成熟。同样,微环境细胞也可能通过这种机制受到影响。因此,铁超载在移植后的植入期也成为重要的问题。本综述旨在更新有关铁超载/铁毒性在HCT环境中在非恶性和恶性中的作用的综合知识。这些疾病引入了在移植的不同阶段中释放游离铁的形式以及相关的细胞损伤的概念。

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