Erratum: Prognostic impact of iron parameters in patients undergoing allo-SCT

Bazuaye, GN; Buser, Andreas; Gerull, Sabine; Thewis, André; Stern, Martin

doi:10.1038/bmt.2012.47

Cited by 3 publications

(4 citation statements)

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“…(2) Even if IOL is assessed by MRI to measure liver iron content, results regarding the prognostic impact of IOL are not consistent [57][58][59][60]. Armand et al concluded that the results presented in their meta-analysis should not be interpreted to imply that iron is irrelevant in HSCT.…”

Section: Iron Overload and Allogeneic Stem Cell Transplantation (Sct)mentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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Section: Iron Overload and Allogeneic Stem Cell Transplantation (Sct)mentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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“…[1][2][3][4][5][6][7] However, it is well established that elevated serum ferritin is not specific for iron overload and ferritin levels do not provide an accurate estimation of body iron stores. 8,9 Similarly, serum ferritin has been shown to be only modestly correlated with iron overload in allogeneic HCT recipients.…”

Section: Introductionmentioning

confidence: 99%

Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI–measured liver iron content

Trottier¹,

Burns²,

DeFor

et al. 2013

Blood

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Key Points• We found no association between iron overload and survival or complications in allogeneic transplant recipients at 1 year posttransplant.• Future studies should use liver iron content to define iron overload instead of ferritin in this population.Using liver magnetic resonance imaging (R2-MRI) to quantify liver iron content (LIC), we conducted a prospective cohort study to determine the association between iron overload and adult allogeneic hematopoietic cell transplantation (HCT) outcomes. Patients received pretransplant ferritin measurements; patients with ferritin >500 ng/mL underwent R2-MRI. Patients were defined as no iron overload (N 5 28) and iron overload (LIC >1.8 mg/g; N 5 60). Median LIC in the iron-overload group was 4.3 mg/g (range, 1.9-25.4). There was no difference in the 1-year probability of overall survival, nonrelapse mortality, relapse, acute or chronic graft-versus-host disease, organ failure, infections, or hepatic veno-occlusive disease between groups. We also found no difference in the cumulative incidence of a composite end point of nonrelapse mortality, any infection, organ failure, or hepatic veno-occlusive disease (1-year cumulative incidence, 71% vs 80%; P 5 .44). In multivariate analyses, iron-overload status did not impact risks of overall mortality (relative risk 5 2.3; 95% confidence interval, 0.9-5.9; P 5 .08). In conclusion, we found no association between pretransplant iron overload and allogeneic HCT outcomes. Future studies in this population should use LIC to define iron overload instead of ferritin. (Blood. 2013;122(9):1678-1684

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“…Many patients with AA and other bone marrow failure syndromes (BMFS) develop transfusion‐related iron overload, especially those with chronic, relapsed, or refractory disease 10,11 . This iatrogenic siderosis affects the heart, liver, and endocrine organs, is a major cause of morbidity, and increases treatment‐related morbidity and mortality, especially in patients requiring allogeneic hematopoietic stem cell transplantation 12 . Laboratory studies suggested that protection of hematopoietic stem and progenitor cells (HSPCs) from iron‐related oxidative damage may be a mechanism for EPAG utility in marrow failure, in addition to stimulation of HSPCs via the TPOR 13 .…”

Section: Introductionmentioning

confidence: 99%

“…10,11 This iatrogenic siderosis affects the heart, liver, and endocrine organs, is a major cause of morbidity, and increases treatment-related morbidity and mortality, especially in patients requiring allogeneic hematopoietic stem cell transplantation. 12 Laboratory studies suggested that protection of hematopoietic stem and progenitor cells (HSPCs) from ironrelated oxidative damage may be a mechanism for EPAG utility in marrow failure, in addition to stimulation of HSPCs via the TPOR. 13 Case reports and small retrospective studies have suggested that iron chelation alone, particularly DFX, may produce hematologic improvement in patients with myelodysplastic syndrome (MDS) or AA.…”

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confidence: 99%

Long‐term eltrombopag for bone marrow failure depletes iron

et al. 2022

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Eltrombopag (EPAG) has been approved for the treatment of aplastic anemia and for immune thrombocytopenia, and a subset of patients require long-term therapy. Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (n = 315) or without EPAG (n = 206) across 11 studies with multiyear follow-up (3.6 vs. 8.5 years, respectively). Duration of EPAG exposure correlated with ferritin reduction (p = 4 Â 10 À14 ) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first-order kinetics with faster clearance (half-life 15.3 months) compared with historical responders (47.5 months, p = 8 Â 10 À10 ). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron-deficiency anemia mimicking relapse, responsive to iron supplementation. | INTRODUCTIONEltrombopag (EPAG) is a nonpeptide human thrombopoietin receptor (TPOR) agonist developed for treatment of thrombocytopenias, most notably chronic immune thrombocytopenia (ITP). 1,2 It has since proven to be active in the treatment of several forms of bone marrow failure, 3,4 with regulatory approvals for single-agent use in immunosuppressive therapy (IST)-refractory severe aplastic anemia (SAA) 5 and in combination with IST as first-line therapy for SAA. 6 However, despite excellent response rates in AA, ITP, and other conditions, patients often remain EPAG-dependent for many years. The consequences of such prolonged EPAG exposure are less defined, particularly at the 3-fold higher doses utilized for AA as compared with ITP.An unexpected property of EPAG is its ability to chelate polyvalent cations, 7 including iron. In vitro, EPAG binds iron with an affinity similar to that of chelators such as deferoxamine (DFO) or deferasirox (DFX). 8 EPAG has significantly greater intracellular uptake, allowing it to access the tissue-confined labile iron pool. Indeed, we and others have shown that tissue-resident iron is readily mobilized into the plasma pool during EPAG treatment, leading to increased serum iron levels and the curious phenomenon of gray-colored blood. 9

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Erratum: Prognostic impact of iron parameters in patients undergoing allo-SCT

Cited by 3 publications

References 0 publications

Iron overload in myelodysplastic syndromes (MDS)

Iron overload in myelodysplastic syndromes (MDS)

Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI–measured liver iron content

Long‐term eltrombopag for bone marrow failure depletes iron

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