Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes

Greenberg, Peter L.; Koller, Charles; Cabantchik, Z. Ioav; Warsi, Ghulam; Glynos, Tara; Paley, Carole; Schiffer, Charles A.

doi:10.1016/j.leukres.2010.06.013

Cited by 49 publications

(43 citation statements)

References 33 publications

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“…In contrast, the values of LPI and eLPI in chelated adults were comparable and generally higher than the younger patients, possibly related to age-dependent decrease in serum antioxidants and higher accumulated body iron burden. This led us to conclude that published values of LPI data in the adult population under active chelation [18,33], can be regarded as representative of total NTBI. However, we cannot exclude the possibility that the presence of both LPI and eLPI in the well-chelated groups may be indicative of sub-optimal chelation, if patients were non-compliant with drug intake 1-2 days before blood testing or vice versa, if they inadvertently took the drug before testing.…”

Section: Discussionmentioning

confidence: 86%

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

Breuer¹,

Ghoti

Shattat³

et al. 2011

American J Hematol

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Non-transferrin bound iron (NTBI) is commonly detected in patients with systemic iron overload whose serum iron-binding capacity has been surpassed. It has been perceived as an indicator of iron overload, impending organ damage and a chelation target in poly-transfused thalassemia patients. However, NTBI is a heterogeneous entity comprising various iron complexes, including a significant redox-active and readily chelatable fraction, which we have designated as ''labile plasma iron'' (LPI). We found that LPI levels can be affected by plasma components such as citrate, uric acid, and albumin. However, the inclusion of a mild metal mobilizing agent in the LPI assay (designated here as ''eLPI''), at concentrations that do not affect transferrin-bound iron, largely overcomes such effects and provides a measure of the full NTBI content. We analyzed three distinct groups of poly-transfused, iron overloaded thalassemia patients: non-chelated children (3-13 yrs, Gaza, Palestine), chelated adolescents-young adults (13-28 yrs, Israel), and chelated adults (27-61 yrs, Israel) for LPI and eLPI. The eLPI levels in all three groups were roughly commensurate (r 2 5 0.61-0.75) with deferrioxamine-detectable NTBI, i.e., DCI. In older chelated patients, eLPI levels approximated those of LPI, but in poly-transfused unchelated children eLPI was notably higher than LPI, a difference attributed to plasma properties affected by labile iron due to lack of chelation, possibly reflecting age-dependent attrition of plasma components. We propose that the two formats of NTBI measurement presented here are complementary and used together could provide more comprehensive information on the forms of NTBI in patients and their response to chelation. Am. J. Hematol. 87:55-61, 2012. V

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Section: Discussionmentioning

confidence: 86%

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

Breuer¹,

Ghoti

Shattat³

et al. 2011

American J Hematol

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“…Chelation may significantly reduce total body iron load and decrease the production of hydroxyl and oxygen radicals, thus lessening cellular and target organ damage and eventually enhancing survival in transfusion-dependent MDS patients [1,2,21,22]. Note, however, that the evidence for the use of chelation therapy in patients with MDS is based, not on randomized controlled trials, but on observational studies; including two recent ones which continue to provide evidence of an beneficial association between chelation therapy and iron status [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence that deferasirox decreases the risk of iron overload in Low and Int-1 IPSS patients [24], removes cardiac iron more effectively, and prevents cardiac iron accumulation [45], and lowers liver iron concentrations and labile plasma iron levels [33] Clinician education about the importance of patient adherence should include this information, as well as such essentials as the potential negative effect of iron overload on heart, liver, and endocrine glands, and the associated increase in mortality risk.…”

Section: Discussionmentioning

confidence: 99%

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

et al. 2011

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 ABSTRACT Transfusion-dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions.Transfusion-dependency is associated with leukemic progression and shorter survival.Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76 and median age at diagnosis of MDS was 74. Patients had received an average of 13.4+7.6 RBC units in the past four months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1550g/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of IPSS, FAB, and/or WHO status, though chelated patients had received more RBC transfusions (p=0.014).Iron chelation therapy may be underutilized in transfusion-dependent patients.

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“…Poprawy takiej nie obserwowano, a wręcz stwierdzano pogorszenie tych parametrów, jeśli wlewy były stosowane w trybie przerywanym, co 2 tygodnie [7]. W innym badaniu, prospektywnym, u 24 chorych na MDS zależnych od transfuzji stwierdzono istotne obniżenie stęże-nia LIC w 24 i 52 miesiące od włączenia leczenia deferazyroksem [53].…”

Section: Wpływ Na Funkcje Narządówunclassified

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

Dwilewicz‐Trojaczek¹,

Waszczuk‐Gajda²

2016

Hematologia

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Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes

Cited by 49 publications

References 33 publications

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

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