Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study

Lee, Jong Wook; Yoon, Sung‐Soo; Shen, Zhi Xiang; Ganser, Arnold; Hsu, Hui‐Chun; El-Ali, Ali; Habr, Dany; Martin, Nicolas; Porter, John B.

doi:10.3324/haematol.2012.077669

Cited by 42 publications

(38 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Systemic iron overload in turn has a suppressive effect on hematopoiesis in patients with hematopoietic failure, with iron-chelation therapy having been found to be beneficial in these patients131415. However, iron overload has little effect on hematopoiesis in patients with hereditary hemochromatosis, which is also a major cause of systemic iron overload due to hepcidin deficiency.…”

Section: Discussionmentioning

confidence: 99%

Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

et al. 2017

View full text Add to dashboard Cite

Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion. Transcriptomic analysis shows abnormal activation of oxidative stress responses and the cell cycle in FBXL5-deficient mouse HSCs as well as downregulation of FBXL5 expression in HSCs of patients with myelodysplastic syndrome. Suppression of iron regulatory protein 2 (IRP2) accumulation in FBXL5-deficient mouse HSCs restores stem cell function, implicating IRP2 as a potential therapeutic target for human hematopoietic diseases associated with FBXL5 downregulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Transfusion-induced IOL is a frequent problem that clinicians have to face in the management of patients affected by hematologic neoplasms 13–15. For example in myelodysplastic syndromes (MDS), many recent studies demonstrated that TD patients in comparison to transfusion independent (TI) ones have a lower survival which is proportional to the degree of transfusion dependence 16–17…”

Section: Introductionmentioning

confidence: 99%

Iron Chelation Therapy With Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

Elli

Belotti

Parma

et al. 2014

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

show abstract

“…There were no reported progressive increases in serum creatinine or hepatic transaminases 62. In addition, a post hoc analysis of the EPIC trial has shown hematologic responses in eleven of 24 patients who received deferasirox as sole therapy 63. The efficacy of deferasirox has also been demonstrated in Diamond–Blackfan anemia and Fanconi anemia 52,64…”

Section: Myelodysplastic Syndromesmentioning

confidence: 97%

Deferasirox: appraisal of safety and efficacy in long-term therapy

Chaudhary¹,

Pullarkat²

2013

JBM

View full text Add to dashboard Cite

Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.

show abstract

Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study

Cited by 42 publications

References 21 publications

Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

Iron Chelation Therapy With Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

Deferasirox: appraisal of safety and efficacy in long-term therapy

Contact Info

Product

Resources

About