Iron overload and iron chelation therapy in patients with myelodysplastic syndrome treated by allogeneic stem‐cell transplantation: Report from the working conference on iron chelation of the Gruppo Italiano Trapianto di Midollo Osseo

Alessandrino, Emilio Paolo; Angelucci, Emanuele; Cazzola, Mario; Porta, Matteo Giovanni Della; Bartolomeo, Paolo Di; Gozzini, Antonella; Malcovati, Luca; Pioltelli, Pietro; Sica, Simona; Bosi, Alberto

doi:10.1002/ajh.22104

Cited by 22 publications

(11 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our observations reveal that hepcidin levels are significantly dysregulated in PMF; despite this, there was evidence of relatively preserved homeostatic control of hepcidin by iron, as reflected by the strongly positive correlation between hepcidin and ferritin levels. This correlation was independent of DIPSS-plus risk stratification, unlike what has been observed in MDS patients stratified by WHO subtype [16,17]; the latter analysis suggested relatively preserved homeostatic control in some MDS subtypes such as refractory anemia, refractory anemia with ringed sideroblasts, and 5q-syndrome but near complete loss of regulation in others such as refractory anemia with excess blasts and chronic myelomonocytic leukemia. The positive correlation between hepcidin and ferritin levels in PMF was found regardless of whether patients were RBC transfusion requiring at the time of sample collection.…”

Section: Discussionmentioning

confidence: 54%

Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis

et al. 2013

View full text Add to dashboard Cite

Iron homeostasis is dysregulated in primary myelofibrosis (PMF), given the high prevalence of anemia, need for red blood cell (RBC) transfusions, and disease-associated inflammatory state. We measured plasma hepcidin levels in 203 consecutive PMF patients at the time of first referral; hepcidin levels were significantly higher as compared to healthy controls (P < 0.0001), and were correlated with hemoglobin of <10 g/dL, RBC transfusion requirement, serum ferritin of >500 mg/L, higher dynamic international prognostic scoring system (DIPSS)-plus risk category, the presence of circulating blasts, age of >65 years, and leukocyte count of <4 3 10 9 /L. Increased hepcidin levels predicted for inferior survival independent of six out of the eight DIPSS-plus prognostic parameters (hazard ratio [HR] 5 1.8; P 5 0.02), but not when RBC transfusion requirement, hemoglobin of <10 g/dL, or increased serum ferritin were included in the Cox model. Multivariable analysis that considered the four overlapping prognostic variables revealed that increased hepcidin (HR 5 1.9; P 5 0.03) and increased ferritin (HR 5 2.3; P 5 0.04), but not hemoglobin of <10 g/dL or RBC transfusion requirement, independently retained their significance for predicting survival. Accordingly, increased levels of both hepcidin and serum ferritin (seen in 29% of patients) predicted inferior survival independent of DIPSS-plus or increased inflammatory cytokine levels (HR 5 2.4; P 5 0.002), and could be considered in future prognostic models for PMF. Am. J.

show abstract

Section: Discussionmentioning

confidence: 54%

Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…We therefore conclude that although accepted widely (16) and recommend by several clinical guidelines (18,19), a ferritin level of 1,000 ng/mL or more is not a reliable marker for SIO in patients with AML and MDS, especially under circumstances of ongoing inflammation. According to our data, higher thresholds such as those proposed by the National Comprehensive Cancer Network (20) are better suited for identifying severely iron-overloaded patients before allo-SCT.…”

Section: Discussionmentioning

confidence: 77%

MRI-Based Liver Iron Content Predicts for Nonrelapse Mortality in MDS and AML Patients Undergoing Allogeneic Stem Cell Transplantation

Wermke

Schmidt

Middeke

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Retrospective, surrogate marker-based studies have found inconsistent associations between systemic iron overload (SIO) and adverse outcome in patients undergoing allogeneic stem cell transplantation (allo-SCT). As a consequence, the impact of SIO in this context remains under debate. The aim of this study was to test whether the objective pretransplant quantification of liver-iron content (LIC) by magnetic resonance imaging (MRI) could circumvent these limitations and conclusively define the prognostic relevance of SIO.Experimental Design: The correlation between pretransplant LIC and surrogate parameters as well as the impact of SIO on posttransplant outcome was assessed within an observational study of patients (n ¼ 88) with either myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allo-SCT.Results: Ferritin levels of 1,000 ng/mL or more provided only poor specificity (31.8%) for predicting elevated LIC (!125 mmol/g) and even higher thresholds (!2,500 ng/mL) lacked an association with nonrelapse mortality (NRM). In contrast, LIC 125 mmol/g or more was a significant risk factor for NRM in uni-and multivariate analysis (HR ¼ 2.98; P ¼ 0.016). Multivariate Cox-regression further showed that LIC 125 mmol/g or more was associated with a decreased overall survival (HR ¼ 2.24, P ¼ 0.038), whereas ferritin or transfusion burden were not.Conclusions: SIO reflected by LIC is an independent negative prognostic factor for posttransplant outcome in patients with AML and MDS undergoing allo-SCT. Therefore, MRI-based LIC, and not interference-prone serum markers such as ferritin, should be preferred for pretransplant risk stratification and patient selection in future clinical trials.

show abstract

“…We suggest instead that the present study should serve as the impetus for the design of next-generation studies that do not rely primarily on SF measurement, and that explore, through careful and creative design, alternative mechanisms through which iron may influence HCT outcomes. Furthermore, several groups have already reported on the use of(26–30) or recommendation for(31) chelation therapy in the pre or post-HCT setting. Our results may weaken the premise for chelation studies in general transplant populations, and emphasize the need to design future chelation studies with a broad array of correlative endpoints that could uncover possible effects of chelation beyond simply the reduction in iron stores.…”

Section: Resultsmentioning

confidence: 99%

Iron Overload in Allogeneic Hematopoietic Cell Transplantation Outcome: A Meta-Analysis

Armand

Kim

Virtanen

et al. 2014

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

An elevated ferritin before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and non-relapse mortality (NRM). Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC>7 mg/gdw (primary endpoint) was 1.4 (p=0.18). In contrast, ferritin >1000 ng/ml was a significant prognostic factor (HR for mortality 1.7, p=0.036). There was, however, no significant association between ferritin>2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT.

show abstract

Iron overload and iron chelation therapy in patients with myelodysplastic syndrome treated by allogeneic stem‐cell transplantation: Report from the working conference on iron chelation of the Gruppo Italiano Trapianto di Midollo Osseo

Cited by 22 publications

References 58 publications

Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis

Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis

MRI-Based Liver Iron Content Predicts for Nonrelapse Mortality in MDS and AML Patients Undergoing Allogeneic Stem Cell Transplantation

Iron Overload in Allogeneic Hematopoietic Cell Transplantation Outcome: A Meta-Analysis

Contact Info

Product

Resources

About