Iron overload in myelodysplastic syndromes: A Canadian consensus guideline

Wells, Richard A.; Leber, Brian; Buckstein, Rena; Lipton, Jeffrey H.; Hasegawa, Wanda; Grewal, Kuljit; Yee, Karen; Olney, Harold J.; Larratt, Loree; Vickars, Linda M.; Tinmouth, Alan

doi:10.1016/j.leukres.2008.02.021

Cited by 48 publications

(50 citation statements)

References 67 publications

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“…To further clarify the role of ICT in PMF it is important to confirm a beneficial effect in prospective trials. While there are no guidelines for the initiation and use of ICT in PMF, MDS guidelines [57][58][59][60][61] suggest a ferritin level be obtained at diagnosis and regular intervals. Baseline investigations should also include an evaluation of cardiac function [40] and newer modalities, were available, including T2…”

Section: Discussionmentioning

confidence: 99%

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy

Leitch

Chase

Goodman

et al. 2009

Hematological Oncology

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Many patients with primary myelofibrosis (PMF) become red blood cell (RBC) transfusion dependent (TD), risking iron overload (IOL). Iron chelation therapy (ICT) may decrease the risk of haemosiderosis associated organ dysfunction, though its benefit in PMF is undefined. To assess the effect of TD and ICT on survival in PMF, we retrospectively reviewed 41 patients. Clinical data were collected from the database and by chart review. The median age at PMF diagnosis was 64 (range 43-86) years. Median white blood cell (WBC) count at diagnosis was 7.6 (range 1.2-70.9) x 10(9)/L; haemoglobin 104 (62-145) G/L; platelets 300 (38-2088) x 10(9)/L. Lille, Strasser, Mayo and International Prognostic System (IPS) scores were: low risk, n = 15, 8, 11, 3; intermediate, n = 15, 19, 9, 16; high, n = 5, 11, 5, 7; respectively. Primary PMF treatment was: supportive care, n = 23; hydroxyurea, n = 10; immunomodulatory, n = 4; splenectomy, n = 2. Sixteen patients were RBC transfusion independent (TI) and 25 TD; of these 10 received ICT for a median of 18.3 (0.1-117) months. Pre-ICT ferritin levels were a median of 2318 (range 263-8400) and at follow up 1571 (1005-3211 microg/L (p = 0.01). In an analysis of TD patients, factors significant for overall survival (OS) were: WBC count at diagnosis (p = 0.002); monocyte count (p = 0.0001); Mayo score (p = 0.05); IPS (p = 0.02); number of RBC units (NRBCU) transfused (p = 0.02) and ICT (p = 0.003). In a multivariate analysis, significant factors were: NRBCU (p = 0.001) and ICT (p = 0.0001). Five year OS for TI, TD-ICT and TD-NO ICT were: 100, 89 and 34%, respectively (p = 0.003). The hazard ratio (HR) for receiving >20 RBCU was 7.6 (95% Confidence Intervals [CI] 1.2-49.3) and for ICT was 0.15 (0.03-0.77). In conclusion, 61% of PMF patients developed RBC-TD which portended inferior OS; however patients receiving ICT had comparatively improved OS, suggesting a clinical benefit. Prospective studies of IOL and the impact of ICT in PMF are warranted.

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Section: Discussionmentioning

confidence: 99%

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy

Leitch

Chase

Goodman

et al. 2009

Hematological Oncology

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“…5 Various clinical practice guidelines recommend the use of iron chelation therapy in lower-risk MDS patients. [6][7][8][9][10][11][12][13][14][15] In addition to reports of reduction in iron burden, 16,17 a number of recently published case reports and studies have reported improvements in hematologic parameters and transfusion requirements during iron chelation therapy with deferasirox. [17][18][19][20][21][22][23][24][25][26] There is also limited evidence of hematologic improvement in patients with MDS treated with deferoxamine, 27,28 although the exact mechanism of the hematologic response to iron chelators is unknown.…”

Section: Introductionmentioning

confidence: 99%

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

et al. 2012

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BackgroundReductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on these reductions/improvements have been limited to case reports and small studies. Design and MethodsTo explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade ® (EPIC) study using International Working Group 2006 criteria. ResultsTwo-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. ConclusionsThis analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.Key words: myelodysplastic syndromes, deferasirox, iron overload, iron chelation therapy, hematologic response. Haematologica 2012;97(9):1364-1371. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Gattermann N, Finelli C, Della Porta M, Fenaux P, Stadler M, Guerci-Bresler A, Schmid M, Taylor K, Vassilieff D, Habr D, Marcellari A, Roubert B, and Rose C. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

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“…Th erefore expert panels were convened to use these data to create guidelines for clinical practice. Several of these guidelines from international and national study groups have been published [2][3][4][5][6][7][8][9][10].…”

Section: Comparison Of Guidelinesmentioning

confidence: 99%

“…Despite the ongoing introduction of new therapies oriented at the pathophysiological features of this disease such as demethylating agents or immunomodulatory drugs and some progress in stem cell transplantation, the majority of patients are still being chronically transfused which inevitably leads to iron overload [1]. Given the lack of data from prospective trials on the eff ects of chelation therapy on overall survival in MDS a number of guidelines for the use of chelators have been published or are being developed [2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Iron chelation therapy in myelodysplastic syndromes: evidence-based rationale and comparison of guidelines

Pfeilstöcker

2010

memo

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Iron overload in myelodysplastic syndromes: A Canadian consensus guideline

Cited by 48 publications

References 67 publications

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Iron chelation therapy in myelodysplastic syndromes: evidence-based rationale and comparison of guidelines

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