Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry

Marlijn Hoeks, Ge Yu, Saskia Langemeijer, Simon Crouch, Louise de Swart, Pierre Fenaux, Argiris Symeonidis, Jaroslav Čermák, Eva Hellström-Lindberg, Guillermo Sanz, Reinhard Stauder, Mette Skov Holm, Moshe Mittelman, Krzysztof Mądry, Luca Malcovati, Aurelia Tatic, Antonio Medina Almeida, Ulrich Germing, Aleksandar Savic, Njetočka Gredelj ŠimecDominic Culligan, Raphael Itzykson, Agnes Guerci-Bresler, Borhane Slama, Arjan van de Loosdrecht, Corine van Marrewijk, Jackie Droste, Nicole Blijlevens, Marian van Kraaij, David Bowen, Theo de Witte, Alex Smith, EUMDS Registry Participants

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.

Original languageEnglish
Pages (from-to)640-651
Number of pages12
JournalHaematologica
Volume105
Issue number3
Early online date5 Jul 2019
DOIs
Publication statusPublished - 1 Mar 2020

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