Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM

Rosé, Christian; Bréchignac, Sabine; Vassilief, D.; Pascal, Laurent; Stamatoullas, Aspasia; Guerci, Agnès; Larbaa, Dalila; Dreyfus, François; Beyne‐Rauzy, Odile; Chaury, M.P.; Roy, Lydie; Chèze, Stéphane; Morel, Pierre; Fenaux, Pierre

doi:10.1016/j.leukres.2009.12.004

Cited by 202 publications

(162 citation statements)

References 38 publications

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“…The fact that, until recently, iron chelation treatment recommendations in MDS were based on limited data further complicates the picture (evidence grade B, level III) [18]. Nowadays, several comparative studies have shown that mortality is higher in heavily iron-overloaded patients [19,20] and that chelation treatment seems to improve survival in MDS patients [16,21]. The guidelines published to date regarding IO treatment agree that iron chelation therapy is indicated in patients with a ferritin level of 1,000 μg/L or more and/or who have received a transfusion of two units per month of PRBC for at least 1 year [16,21].…”

Section: Discussionmentioning

confidence: 99%

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

et al. 2009

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. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements. Annals of Hematology, Springer Verlag, 2009, 89 (2) Abstract The main objective of the study was to analyze the incidence of iron overload (IO) and its management in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) before the license of deferasirox. This observational, cross-sectional, and multicenter study was conducted from January to May 2007 in 81 Spanish hospitals. Eligible patients had a low or intermediate-1 risk score and had to have received at least ten units of packed red blood cell (PRBC). Of the 549 patients analyzed, 75% had received more than 20 PRBC units since diagnosis; 14% had IO at diagnosis and 58% at last follow-up. Thirty-eight percent of patients received chelation therapy; of those, 92% were treated with desferrioxamine. Ferritin levels at the start of chelation therapy were higher than 1,000 μg/L in 76% and over 2,500 μg/L in 24% of patients. Of the 202 patients who received some form of chelation therapy, ferritin levels increased from a mean±SD of 1,986±1,398 to 2,480± 1,648 μg/L at last follow-up in 86% (p<0.001). In the remaining 29 patients treated with a minimally effective therapy, ferritin levels did not increase. Of these, only 11 patients received such therapy lasting more than 12 months. In conclusion, most low-risk transfusion-dependent MDS patients develop IO, but only a minority receives a minimally effective and timely iron chelation therapy.

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Section: Discussionmentioning

confidence: 99%

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

et al. 2009

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“…List et al [27] Low/lnt-1 15% (n = 173) 15% (n = 52) 22% (n = 77) Gattermann et al [28] Low/lnt-1 21.5% (n = 247) 22% (r = 50) 13% (n = 100) Nolte et al [29] Low/lnt-1 11% (n = 50) NR NR Angelucci et al [30] Low/lnt-1 Transfusion independence in 15.5% (n = 152) Table 2 Clinical studies showing that iron chelation improves survival in patients with lower risk MDS [32][33][34][35][36][37][38][39][40].…”

Section: Is There a Survival Benefit From Chelation Therapy (Ict)?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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“…Consequently, several retrospective and observational studies have suggested a beneficial influence of iron chelation on mortality and morbidity in MDS patients with transfusional IO [17][18][19][20][21][22][23][24].…”

Section: Potential Benefits Of Iron Chelation In Transfusion Dependenmentioning

confidence: 99%

“…Recently, several retrospective but also some prospective studies have indicated, that transfusion dependent patients with MDS might benefit from consequent iron chelation with regard to morbidity and mortality [17][18][19][20][21][22][23][24]. However, gastrointestinal adverse events leading to reduced quality of life in these patients are associated with low treatment adherence and are considered as a major obstacle in achieving consequent and effective iron chelation with DFX.…”

Section: Introductionmentioning

confidence: 99%

Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with Deferasirox in transfusion dependent patients with myelodysplastic syndrome – Emphasis on optimized dosing schedules and new formulations

Nolte¹,

Angelucci²,

Breccia³

et al. 2015

Leukemia Research

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a b s t r a c tMyelodysplastic syndromes (MDS) are oligoclonal hematopoietic disorders characterized by peripheral cytopenias with anemias being the most prevalent feature. The majority of patients will depend on regular transfusions of packed red blood cells (PRBC) during the course of the disease. Particularly patients with MDS and low risk for transformation into acute myeloid leukemia and low risk of early death will receive PRBC transfusions on a regular basis, which puts them at high risk for transfusional iron overload. Transfusion dependence has been associated with negative impact on organ function and reduced life expectancy.Recently, several retrospective but also some prospective studies have indicated, that transfusion dependent patients with MDS might benefit from consequent iron chelation with regard to morbidity and mortality. However, low treatment adherence due to adverse events mainly gastrointestinal in nature is an important obstacle in achieving sufficient iron chelation in MDS patients. Here, we will summarize and discuss the existing data on Deferasirox in low risk MDS published so far and provide recommendations for optimal management of gastrointestinal adverse events during iron chelation aiming at improving treatment compliance and, hence, sufficiently removing excess iron from the patients.

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Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM

Cited by 202 publications

References 38 publications

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

Iron overload in myelodysplastic syndromes (MDS)

Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with Deferasirox in transfusion dependent patients with myelodysplastic syndrome – Emphasis on optimized dosing schedules and new formulations

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