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Iron Metabolism & its Disorders
Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort
Maddalena Casale,1 Gian Luca Forni,2 Elena Cassinerio,3 Daniela Pasquali,4 Raffaella Origa,5 Marilena Serra,6 Saveria Campisi,7 Angelo Peluso,8 Roberta Renni,9 Alessandro Cattoni,10 Elisa De Michele,11 Massimo Allò,12 Maurizio Poggi,13 Francesca Ferrara,14 Rosanna Di Concilio,15 Filomena Sportelli,16 Antonella Quarta,17 Maria Caterina Putti,18 Lucia Dora Notarangelo,19 Antonella Sau,20 Saverio Ladogana,21 Immacolata Tartaglione,1 Stefania Picariello,1 Alessia Marcon,3 Patrizia Sturiale,22 Domenico Roberti,1 Antonio Ivan Lazzarino23 and Silverio Perrotta1
1Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy; 2Center of Microcitemia and Congenital Anemias, Galliera Hospital, Genoa, Italy; 3Rare Diseases Center, General Medicine Unit, IRCCS Ca’ Granda Ospedale Maggiore Policlinico Section co, Milan, Italy; 4Endocrinology Unit, Department of Advanced Medical and Surgical Sciences, University “ Luigi Vanvitelli”, Naples, Italy; 5Thalassemia Center, Pediatric Hospital A CAO, AOG Brotzu, Cagliari, Italy; 6Thalassemia Center, Department of Internal Medicine, Hospital "V. Fazzi", Lecce, Italy; 7Thalassemia Center, Hospital Umberto I, Siracusa, Italy; 8Center of Microcitemia, POC SS.Annunziata - ASL TA, Taranto, Italy; 9Thalassemia Center, Department of Internal Medicine, Hospital F.Ferrari, Casarano, Italy; 10Department of Pediatrics, Università degli Studi di Milano Bicocca, Fondazione Monza e Brianza per il Bambino e la sua Mamma, Azienda Ospedaliera San Gerardo, Monza, Italy; 11Immunotransfusion Medicine Unit, AOU OO.RR. S. Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy; 12Center of Microcitemia, Hospital ASL 5, Crotone, Italy; 13Department of Endocrinology, Sant'Andrea Hospital, Rome, Italy; 14Department of Internal Medicine, Policlinico Hospital of Modena, Modena, Italy; 15Department of Pediatrics, Hospital Umberto I, Nocera, Italy; 16Immunotransfusion Unit, Hospital Riuniti, Foggia, Italy; 17Center for Microcythemia, Iron Metabolism Disorders, Gaucher Disease - Hematology and Transplantation Unit, "A. Perrino" Hospital, Brindisi, Italy; 18Department of Women's and Child's Health (DSDB), University Hospital, Padova, Italy; 19Hematology Oncology Unit, Children's Hospital, ASST Spedali Civili, Brescia, Italy; 20Department of Pediatric Hematology and Oncology, Hospital “Spirito Santo”, Pescara, Italy; 21Pediatric Oncohematology Unit, “Casa Sollievo della Sofferenza” Hospital, IRCCS, San Giovanni Rotondo, Italy; 22SSD Microcitemia Center, G.O.M Reggio Calabria, Reggio Calabria, Italy and 23EPISTATA – Agency for Clinical Research and Medical Statistics, London, UK
ABSTRACT
Transfusion-dependent patients typically develop iron-induced car- diomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion- dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median dura- tion of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine dis- eases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3–13.1). Multiple Cox regression analysis identified three key predictors: age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1–1.3, P=0.005), the serum con- centration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1–1.4, P<0.001) regardless the kind of dis- ease incident, while the number of previous endocrine diseases showed a negative linear effect: the higher the number of diseases at baseline the lower the chance of developing further diseasess (adjusted HR for unit
Ferrata Storti Foundation
Haematologica 2022 Volume 107(2):467-477
Correspondence:
MADDALENA CASALE
maddalena.casale@unicampania.it
Received: September 18, 2020. Accepted: December 22, 2020. Pre-published: January 7, 2021.
https://doi.org/10.3324/haematol.2020.272419 ©2022 Ferrata Storti Foundation
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