title: Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.
abstract: The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*<20 ms, in patients with thalassemia, SCA, or MDS. Patient inclusion criteria were an accurate record of erythrocyte concentrates (ECs) received, a transfusion history >8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.
authors.affiliation: Pediatrics Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Mariane
authors.initials: M
authors.lastname: de Montalembert
authors.affiliation: Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Ribeil
authors.affiliation: Pediatrics Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Brousse
authors.affiliation: Hematology Department, Hôpital d'Adultes du Brabois, Vandoeuvre les Nancy, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Guerci-Bresler
authors.affiliation: Centre Henri Becquerel, Rouen, France.
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.affiliation: Pediatric Oncology and Hematology Unit, Hôpital Charles Nicolle, Rouen, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
authors.affiliation: Pediatric Oncology and Hematology Unit, Hôpital Charles Nicolle, Rouen, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Dumesnil
authors.affiliation: Department of Biochemistry, Hôpital Charles Nicolle, Rouen, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Lahary
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, CHU, Limoges, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touati
authors.affiliation: Service des Maladies du Sang, Hôpital Haut-Levêque, Pessac, France.
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.affiliation: Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.|Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France.|Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France.|INSERM UMR 1163, Laboratory of Human Lymphopoiesis, Paris France.
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana
authors.affiliation: Département de Pharmacologie clinique et toxicologique, CHU, Bordeaux, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Chauzit
authors.affiliation: Paris Descartes Clinical Research Unit, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Baptiste
authors.affiliation: Laboratory of Excellence GR-Ex, Paris, France.|INSERM UMR 1149/ERL. CNRS 8252, Centre de Recherche sur l'inflammation, Paris, France.|French center for Porphyria, Louis Mourier Hospital, Assistance Publique-Hôpitaux de Paris, Colombes, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lefebvre
authors.affiliation: Laboratory of Excellence GR-Ex, Paris, France.|INSERM UMR 1149/ERL. CNRS 8252, Centre de Recherche sur l'inflammation, Paris, France.|French center for Porphyria, Louis Mourier Hospital, Assistance Publique-Hôpitaux de Paris, Colombes, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Puy
authors.affiliation: Paris Descartes Clinical Research Unit, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.affiliation: Laboratory of Excellence GR-Ex, Paris, France.|INSERM UMR 1149/ERL. CNRS 8252, Centre de Recherche sur l'inflammation, Paris, France.
authors.forename: Zoubida
authors.initials: Z
authors.lastname: Karim
authors.affiliation: Radiology Department, Hopital Huriez, CHRU, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ernst
authors.affiliation: Hématologie clinique, Hôpital Saint Vincent de Paul, Université Catholique de Lille, Lille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000503:physiopathology; D001803:Blood Transfusion; D002648:Child; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007501:Iron / Q000097:blood; D007502:Iron Chelating Agents; D019190:Iron Overload / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D013789:Thalassemia / Q000097:blood* / Q000503:physiopathology
chemical_list: D007502:Iron Chelating Agents; D007501:Iron