Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes

Delforge, Michel; Selleslag, Dominik; Béguin, Yves; Triffet, Agnès; Mineur, Philippe; Theunissen, Koen; Graux, Carlos; Trullemans, Fabienne; Boulet, Dominique; Eygen, Koen Van; Noens, Lucien; Steenweghen, Steven Van; Lemmens, Jan; Pierre, P.; Dhondt, Rutger; Ferrant, Augustin; Deeren, Dries; Velde, Ann Van de; Wynendaele, Wim; André, Marc; Bock, R. De; Efira, André; Breems, Dimitri; Deweweire, Anne; Geldhof, Kurt; Pluymers, Wim; Harrington, Amanda; MacDonald, Karen; Abraham, Ivo; Ravoet, Christophe

doi:10.1016/j.leukres.2014.02.003

Cited by 56 publications

(33 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Early results from prospective studies of DFX in LR-MDS patients with IO demonstrated significant reductions in serum ferritin, liver iron concentration and hepatic transaminases within 3-6 months, but these studies had limited follow-up and did not report on survival or organ damage outcomes [21][22][23][24]. ICT has been associated in observational studies with improved survival in MDS patients with IO [5][6][25][26][27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

et al. 2015

View full text Add to dashboard Cite

Aims: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. Patients & methods: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving ≥20 blood units were observed until death or end of study. Marginal structural models were used for estimation. Results: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983-0.996; p = 0.001). Conclusion: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold.

show abstract

Section: Discussionmentioning

confidence: 99%

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

et al. 2015

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…1 Transfusion dependency has been recognized as an independent prognostic factor for the survival of patients with MDS 2 and iron chelation therapy leads to the improvement of survival in these patients. [3][4][5] Increased frequency of two hemochromatosis (HFE) gene mutations, C282Y and H63D, among MDS patients was reported by Varkony et al 6 This finding was confirmed only for a subset of MDS patients with RARS 7 and could not be confirmed by other author groups for MDS patients in general. [7][8][9] Differences were attributed to a different geographic distribution of the HFE gene mutations among populations.…”

Section: Introductionmentioning

confidence: 94%

Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome

et al. 2016

View full text Add to dashboard Cite

Conflict of interest statementThe authors declare that there are no conflicts of interest. AcknowledgementsThe authors would like to thank Wilma Miletić for help with manuscript preparation. 2 AbstractObjectives: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS.Methods: 36 newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene.Results: Mutations were present in 11 out of 36 patients (31%), which was not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (p=0.039) and lower TIBC (p=0.018). Ferritin was found to be higher for the untransfused mutated patients (p=0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (p=0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival (OS) in addition to a poorer leukemia free survival (LFS) (p=0.004 and p=0.003, respectively). Discussion:The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anaemia.The effect of mutations on survival could be mediated by changes in iron metabolism. Conclusion:The HFE gentopye may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy.

show abstract

Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes

Cited by 56 publications

References 25 publications

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

Iron overload in myelodysplastic syndromes (MDS)

Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome

Contact Info

Product

Resources

About