Hematology and Stem Cell Transplant Center, AORMN Hospital, Pesaro, Italy.
Hematology and Stem Cell Transplant Center, AORMN Hospital, Pesaro, Italy.
Transplant Cell Ther. 2021 May;27(5):371-379. doi: 10.1016/j.jtct.2020.11.007. Epub 2020 Dec 11.
Many patients with hematologic malignancies receive RBC transfusion support, which often causes systemic and tissue iron toxicity. Because of their compromised bone marrow function, hematopoietic stem cell transplant (HSCT) recipients are especially vulnerable to excess iron levels. Iron toxicity may compromise transplant engraftment and eventually promote relapse by mediating oxidative and genotoxic stress in hematopoietic stem cells (HSCs) and further impairing the already dysfunctional bone marrow microenvironment in HSCT recipients. Iron toxicity is thought to be primarily mediated by its ability to induce reactive oxygen species and trigger inflammation. Elevated iron levels in the bone marrow can decrease the number of HSCs and progenitor cells, as well as their clonogenic potential, alter mesenchymal stem cell differentiation, and inhibit the expression of chemokines and adhesion molecules involved in hematopoiesis. In vivo, in vitro, and clinical studies support the concept that iron chelation therapy may limit iron toxicity in the bone marrow and promote hematologic improvement and engraftment in HSCT recipients. This review will provide an overview of the current knowledge of the detrimental impact of iron toxicity in the setting of HSCT in patients with hematologic malignancies and the use of iron restriction approaches to improve transplant outcome.
许多血液系统恶性肿瘤患者需要接受红细胞输血支持，这往往会导致全身和组织铁毒性。由于骨髓功能受损，造血干细胞移植（HSCT）受者尤其容易发生铁过量。铁毒性可能会损害移植植入，并通过介导造血干细胞（HSCs）中的氧化和遗传毒性应激，进一步损害 HSCT 受者已经功能失调的骨髓微环境，从而最终促进复发。铁毒性被认为主要是通过其诱导活性氧和引发炎症的能力来介导的。骨髓中升高的铁水平可减少 HSCs 和祖细胞的数量及其克隆形成潜能，改变间充质干细胞分化，并抑制涉及造血的趋化因子和黏附分子的表达。体内、体外和临床研究支持这样一种观点，即铁螯合疗法可能会限制 HSCT 受者骨髓中的铁毒性，并促进血液学改善和植入。本综述将概述血液系统恶性肿瘤患者 HSCT 中铁毒性的有害影响以及限制铁的方法在改善移植结果中的应用。
