From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox

Abstract

Iron chelation therapy (ICT) has become a mainstay in heavily transfused hematological patients, with the aim to reduce iron overload (IOL) and prevent organ damage. This therapeutic approach is already widely used in thalassemic patients and in low-risk Myelodysplastic Syndrome (MDS) patients. More recently, ICT has been proposed for high-risk MDS, especially when an allogeneic bone marrow transplantation has been planned. Furthermore, other hematological and hereditary disorders, characterized by considerable transfusion support to manage anemia, could benefit from this therapy. Meanwhile, data accumulated on how iron toxicity could exacerbate anemia and other clinical comorbidities due to oxidative stress radical oxygen species (ROS) mediated by free iron species. Taking all into consideration, together with the availability of approved oral iron chelators, we envision a larger use of ICT in the near future. The aim of this review is to better identify those non-thalassemic patients who can benefit from ICT and give practical tips for management of this therapeutic strategy.

Clinical view versus guideline adherence in ferritin monitoring and initiating iron chelation therapy in patients with myelodysplastic syndromes

“…Recent research reported similar ICT safety and efficacy in higher‐risk MDS patients compared to lower‐risk MDS patients 33 . Although this retrospective analysis was performed in a small higher‐risk MDS population, it indicates that monitoring potential iron overload is relevant in this patient group, especially since the life expectancy of higher‐risk MDS patients is improving 9,32,33 . Because it is unclear whether the benefits of ICT outweigh its side‐effects in MDS patients and due to the costs of ICT, treating haematologists seem reluctant in providing ICT in MDS patients 19,21,29 .…”

“…29 It has been described that iron overload is correlated with decreased survival, higher incidence of infections, ineffective erythropoiesis and an increased risk of leukemic transformation of MDS due to genomic alterations. 9,19,[30][31][32] The TEL-ESTO study showed positive clinical effects of ICT in lower-risk MDS patients, and another study noted better overall survival amongst patients who received ICT as recommended by guidelines; better monitoring of potential iron overload might therefore prevent iron overload-related effects that impair patient life expectancy. 9,19,31 In our study population, the decision to initiate ICT was most likely influenced by the clinical performance of patients.…”

“… 33 Although this retrospective analysis was performed in a small higher‐risk MDS population, it indicates that monitoring potential iron overload is relevant in this patient group, especially since the life expectancy of higher‐risk MDS patients is improving. 9 , 32 , 33 Because it is unclear whether the benefits of ICT outweigh its side‐effects in MDS patients and due to the costs of ICT, treating haematologists seem reluctant in providing ICT in MDS patients. 19 , 21 , 29 In this study, plasma ferritin levels were monitored more frequently in patients <80 years of age or with lower‐risk MDS after receiving more than 20 transfusions, and it appears that fitter patients, also represented in clinical performance, were more likely to be monitored for potential iron overload.…”

Advances in Evaluation of Antioxidant and Toxicological Properties of Stryphnodendron rotundifolium Mart. in Drosophila melanogaster Model

“…However, renal failure and cytopenias have been reported in patients receiving DFX oral suspension tablets [ 48 ]. DFX treatments have shown feasibility and efficacy in patients with thalassemia intermedia [ 49 ], myelofibrosis (MF), myelodysplastic syndrome (MDS) [ 50 , 51 , 52 ], and myeloproliferative neoplasms in fibrotic phase (MPN) [ 53 ]. Due to reports of serious adverse reactions, DFX was discontinued in 2020; however, it is available as a generic drug [ 54 ].…”

Incidence of blast phase in myelofibrosis patients according to anemia severity at ruxolitinib start and during therapy

“…41 As in other chronic hematological malignancies, iron overload due to red blood cell transfusions has been associated with reduced survival also in MF. 44 Indeed, in the presence of iron overload, there is an abnormal release of reactive oxygen species in the bone marrow, resulting in impaired marrow function. 45 Additionally, a recent Italian study has shown that use of iron chelation therapy (deferasirox) in combination with RUX in anemic MF patients can increase Hb levels and achieve iron chelation responses that are associated with improved survival.…”