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Haematologica. 2019 Jul 5. pii: haematol.2018.212332. doi: 10.3324/haematol.2018.212332. [Epub ahead of print]

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

Author information

1
Centre for Clinical Transfusion Research, Sanguine Research, Leiden, The Netherlands.
2
Department of Health Sciences, University of York, York, United Kingdom.
3
Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands.
4
Service d'Hématologie, Hôpital Saint-Louis and Université Paris 7, Paris, France.
5
Department of Medicine, University of Patras Medical School, Patras, Greece.
6
Dept. of Clinical Hematology, Inst. of Hematology & Blood Transfusion, Praha, Czech Republic.
7
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
8
Department of Haematology, Hospital Universitario y Politecnico La Fe, Valencia, Spain.
9
Dept. of Haematology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
10
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
11
Tel Aviv Sourasky (Ichilov) Medical Center and Sackler Medical Faculty, Tel Aviv University, Israel.
12
Dept. of Haematology, Oncology and Internal Medicine, Warszawa Medical University, Warszawa, Poland.
13
Department of Hematology Oncology, Policlinico San Matteo, University of Pavia, Italy.
14
Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
15
Department of Hematology, Hospital da Luz, Lisbon, Portugal.
16
Dept. of Haematology, Oncology and Clinical Immunology, Universitätsklinik Dusseldorf, Germany.
17
Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia.
18
Department of Internal Medicine, Merkur University Hospital, Zagreb, Croatia.
19
Department of Haematology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
20
Service Hématologie Seniors, Hôpital Saint-Louis, Université Paris 7, France.
21
Service Hématologie, Centre Hospitalier Universitaire Brabois Vandoeuvre, Nancy, France.
22
Service Hématologie, Centre Hospitalier d'Avignon, Avignon, France.
23
Dept. of Hematology, Cancer Center Amsterdam VU University Medical Center, The Netherlands.
24
Unit Transfusion Medicine, Sanquin Blood Bank, Amsterdam, the Netherlands.
25
St. James's Institute of Oncology, Leeds Teaching Hospitals, Leeds, United Kingdom.
26
Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands t.dewitte@ncmls.ru.nl.

Abstract

Iron overload due to red blood cell transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome patients. Many studies suggested improved survival after iron chelation therapy, but valid data are limited. The aim of this study was to assess the effect of iron chelation on overall survival and hematological improvement in lower-risk myelodysplastic syndrome 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, treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for overall survival for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative red blood cell transfusions, IPSS-R, and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, red blood cell transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R and additionally corrected for cumulative red blood cell transfusions and presence of ringed sideroblasts, demonstrated a significantly improved overall survival 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 overall survival and hematopoiesis in transfused lower-risk myelodysplastic syndrome patients. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

KEYWORDS:

Myelodysplastic Syndromes; iron chelation; iron overload; lower-risk; overall survival

PMID:
31278207
DOI:
10.3324/haematol.2018.212332
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