P-240 Haematopoietic improvement following iron chelation may result from deferasirox-induced restoration of T cell immune surveillance

Opat, Stephen; Mifsud, Nicole A.; Banerjee, Anirban; Bird, Robert; Forsyth, Cecily; Szer, Jeffrey; Tam, Constantine S.; Kellner, S.; Grigg, Andrew; Motum, Penelope; Bentley, Mark; Grigoriadis, George

doi:10.1016/s0145-2126(13)70287-x

Cited by 2 publications

(3 citation statements)

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“…41,42 Jensen et al have shown a correlation between hematological improvement and a reduction in the liver iron concentration (LIC) as measured by magnetic resonance imaging (MRI). 47 However, the most commonly adopted mechanism is the reduction in oxidative stress resulting from the decrease in iron content. 42 Multiple mechanisms have been proposed to explain the effect of iron chelation on hematopoiesis.…”

Section: Pathogenesis Of Iron Overload In Patients With Mds and Its Rmentioning

confidence: 99%

“…These include the repression of the mammalian target of rapamycin (mTOR) pathway reducing myeloid neoplastic tumor volume, 44 inhibition of signaling via the nuclear factor jB (NF-jB) by deferasirox, 45 the promotion of iron release from stores, an increase in erythropoietin levels, 46 and a possible direct effect on the malignant clone and its bone marrow niche through alterations in immune surveillance. 47 However, the most commonly adopted mechanism is the reduction in oxidative stress resulting from the decrease in iron content. Ineffective erythropoiesis is induced by iron overload, and correlates with the presence of ROS in precursor cells.…”

Section: Pathogenesis Of Iron Overload In Patients With Mds and Its Rmentioning

confidence: 99%

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Iron overload in patients with myelodysplastic syndromes: An updated overview

Moukalled

Rassi

Temraz

et al. 2018

Cancer

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Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication.

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Section: Pathogenesis Of Iron Overload In Patients With Mds and Its Rmentioning

confidence: 99%

Section: Pathogenesis Of Iron Overload In Patients With Mds and Its Rmentioning

confidence: 99%

Iron overload in patients with myelodysplastic syndromes: An updated overview

Moukalled

Rassi

Temraz

et al. 2018

Cancer

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“…Deferasirox inhibits signaling via the nuclear transcription factor NF κ B; however this effect was not observed with deferoxamine or deferiprone, so it does not account for the HI observed with all three chelators [ 56 ]. In one study, suppression by deferasirox of helper T-type 1 cells and T regulatory cells was seen along with a shift toward a helper T-cell type 2 phenotype, indicating that alterations in immune surveillance may occur [ 57 ]. Also suggested are the following: a direct effect on the neoplastic clone or the bone marrow environment; promotion of iron release from stores allowing use by hemopoietic tissue; and an increase in endogenous EPO levels [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

Kochhar¹,

Leger

Leitch

2015

Case Reports in Hematology

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Background. Hematologic improvement (HI) occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT) but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC) transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient's course in detail and review the literature on HI with chelation. Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

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P-240 Haematopoietic improvement following iron chelation may result from deferasirox-induced restoration of T cell immune surveillance

Cited by 2 publications

References 0 publications

Iron overload in patients with myelodysplastic syndromes: An updated overview

Iron overload in patients with myelodysplastic syndromes: An updated overview

Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

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