Management of age-associated medical complications in patients with β-thalassemia

References

• Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010 Jun 3;115(22):4331–4336.
   PubMed Web of Science ®Google Scholar
• Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480–487.
   PubMed Web of Science ®Google Scholar
• Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet. 2018 Jan 13; 391(10116):155–167.
   PubMed Web of Science ®Google Scholar
• Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct;89(10):1187–1193.
   PubMed Web of Science ®Google Scholar
• Modell B, Khan M, Darlison M. Survival in beta-thalassaemia major in the UK: data from the UK thalassaemia register. Lancet. 2000 Jun 10;355(9220):2051–2052.
   PubMed Web of Science ®Google Scholar
• Marcon A, Motta I, Taher AT, et al. Clinical complications and their management. Hematol Oncol Clin North Am. 2018 Apr;32(2):223–236.
   PubMed Web of Science ®Google Scholar
• Borgna-Pignatti C, Cappellini MD, De Stefano P, et al. Survival and complications in thalassemia. Ann N Y Acad Sci. 2005;1054:40–47.
   PubMed Web of Science ®Google Scholar
• Farmakis D, Aessopos A. Pulmonary hypertension associated with hemoglobinopathies: prevalent but overlooked. Circulation. 2011 Mar 22; 123(11):1227–1232.
   PubMed Web of Science ®Google Scholar
• Morris CR, Vichinsky EP. Pulmonary hypertension in thalassemia. Ann N Y Acad Sci. 2010 Aug;1202:205–213.
   PubMed Web of Science ®Google Scholar
• Koohi F, Kazemi T, Miri-Moghaddam E. Cardiac complications and iron overload in beta thalassemia major patients-a systematic review and meta-analysis. Ann Hematol. 2019 Jun;98(6):1323–1331.
   PubMed Web of Science ®Google Scholar
• Borgna-Pignatti C, Meloni A, Guerrini G, et al. Myocardial iron overload in thalassaemia major. How early to check? Br J Haematol. 2014 Feb;164(4):579–585.
   PubMed Web of Science ®Google Scholar
• Pepe A, Meloni A, Borsellino Z, et al. Myocardial fibrosis by late gadolinium enhancement cardiac magnetic resonance and hepatitis C virus infection in thalassemia major patients. J Cardiovasc Med (Hagerstown). 2015 Oct;16(10):689–695.
   PubMed Web of Science ®Google Scholar
• Amoozgar H, Zeighami S, Haghpanah S, et al. A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. Hematology. 2017 Jan;22(1):25–29.
   PubMed Web of Science ®Google Scholar
• Carpenter JP, He T, Kirk P, et al. On T2* magnetic resonance and cardiac iron. Circulation. 2011 Apr 12;123(14):1519–1528.
   PubMed Web of Science ®Google Scholar
• Kirk P, Roughton M, Porter JB, et al. Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation. 2009 Nov 17;120(20):1961–1968.
   PubMed Web of Science ®Google Scholar
• Meloni A, Favilli B, Positano V, et al. Safety of cardiovascular magnetic resonance gadolinium chelates contrast agents in patients with hemoglobinopathies. Haematologica. 2009 Nov;94(11):1625–1627.
   PubMed Web of Science ®Google Scholar
• Agency EM. EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans. [cited 2019 Oct 18]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/gadolinium_contrast_agents_31/European_Commission_final_decision/WC500240575.pdf
   Google Scholar
• Cassinerio E, Roghi A, Orofino N, et al. A 5-year follow-up in deferasirox treatment: improvement of cardiac and hepatic iron overload and amelioration in cardiac function in thalassemia major patients. Ann Hematol. 2015 Jun;94(6):939–945.
   PubMed Web of Science ®Google Scholar
• Gammella E, Recalcati S, Rybinska I, et al. Iron-induced damage in cardiomyopathy: oxidative-dependent and independent mechanisms. Oxid Med Cell Longev. 2015;2015:230182.
   PubMed Web of Science ®Google Scholar
• Paul A, Thomson VS, Refat M, et al. Cardiac involvement in beta-thalassaemia: current treatment strategies. Postgrad Med. 2019 May;131(4):261–267.
   PubMed Web of Science ®Google Scholar
• Nomani H, Bayat G, Sahebkar A, et al. Atrial fibrillation in beta-thalassemia patients with a focus on the role of iron-overload and oxidative stress: a review. J Cell Physiol. 2019 Aug;234(8):12249–12266.
   PubMed Web of Science ®Google Scholar
• Pepe A, Meloni A, Rossi G, et al. Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: a prospective multicentre study by a multi-parametric approach. Eur Heart J Cardiovasc Imaging. 2018 Mar 1;19(3):299–309.
   PubMed Web of Science ®Google Scholar
• Russo V, Rago A, Papa AA, et al. Electrocardiographic presentation, cardiac arrhythmias, and their management in beta-thalassemia major patients. Ann Noninvasive Electrocardiol. 2016 Jul;21(4):335–342.
   PubMed Web of Science ®Google Scholar
• Cappellini MD, Motta I, Musallam KM, et al. Redefining thalassemia as a hypercoagulable state. Ann N Y Acad Sci. 2010;1202:231–236.
   PubMed Web of Science ®Google Scholar
• Russo V, Papa AA, Rago A, et al. The importance of a correct methodological approach for the arrhythmic risk evaluation in beta thalassemia major patients. Int J Cardiol. 2016 Dec 15;225:107–108.
   PubMed Web of Science ®Google Scholar
• Cappellini MD, Robbiolo L, Bottasso BM, et al. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. 2000 Nov;111(2):467–473.
   PubMed Web of Science ®Google Scholar
• Singer ST, Kuypers FA, Styles L, et al. Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol. 2006 Sep;81(9):670–675.
   PubMed Web of Science ®Google Scholar
• Karimi M, Musallam KM, Cappellini MD, et al. Risk factors for pulmonary hypertension in patients with beta thalassemia intermedia. Eur J Intern Med. 2011 Dec;22(6):607–610.
   PubMed Web of Science ®Google Scholar
• Mokhtar GM, Adly AA, El Alfy MS, et al. N-terminal natriuretic peptide and ventilation-perfusion lung scan in sickle cell disease and thalassemia patients with pulmonary hypertension. Hemoglobin. 2010;34(1):78–94.
   PubMed Web of Science ®Google Scholar
• Souza R, Jardim C, Julio Cesar Fernandes C, et al. NT-proBNP as a tool to stratify disease severity in pulmonary arterial hypertension. Respir Med. 2007 Jan;101(1):69–75.
   PubMed Web of Science ®Google Scholar
• Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67–119.
   PubMed Web of Science ®Google Scholar
• Morris CR, Kim HY, Wood J, et al. Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension. Haematologica. 2013 Sep;98(9):1359–1367.
   PubMed Web of Science ®Google Scholar
• Derchi G, Balocco M, Bina P, et al. Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up. Haematologica. 2014 Feb;99(2):e17–8.
   PubMed Web of Science ®Google Scholar
• Anthi A, Tsangaris I, Hamodraka ES, et al. Treatment with bosentan in a patient with thalassemia intermedia and pulmonary arterial hypertension. Blood. 2012 Aug 16;120(7):1531–1532.
   PubMed Web of Science ®Google Scholar
• Karami H, Darvishi-Khezri H, Kosaryan M, et al. The improvement of pulmonary artery pressure after bosentan therapy in patients with beta-thalassemia and doppler-defined pulmonary arterial hypertension. Int Med Case Rep J. 2019;12:1–7.
   PubMed Web of Science ®Google Scholar
• Gerede DM, Acibuca A, Sayin T, et al. Treatment of pulmonary hypertension in three patients with ss-thalassemia intermedia using pulmonary arterial hypertension-specific medications. Anatol J Cardiol. 2016 Jan;16(1):64–66.
   PubMed Web of Science ®Google Scholar
• Correale M, Zicchino S, Monaco I, et al. Association therapy with macitentan added to sildenafil in a thalassemic patient with pulmonary hypertension. Int J Cardiol. 2016 Oct 1;220:80–81.
   PubMed Web of Science ®Google Scholar
• Jalalian R, Moghadamnia AA, Tamaddoni A, et al. Comparing the efficacy of tadalafil versus placebo on pulmonary artery systolic pressure and right ventricular function in patients with beta-thalassaemia intermedia. Heart Lung Circ. 2017 Jul;26(7):677–683.
   PubMed Web of Science ®Google Scholar
• Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010 Mar 11;115(10):1886–1892.
   PubMed Web of Science ®Google Scholar
• Cappellini MD, Cohen A, Porter J, et al., editors. Guidelines for the management of Transfusion Dependent Thalassaemia (TDT). Nicosia (CY): Thalassaemia International Federation; 2014.
   Google Scholar
• Taher AT, Cappellini MD. How I manage medical complications of beta-thalassemia in adults. Blood. 2018 Oct 25; 132(17):1781–1791.
   PubMed Web of Science ®Google Scholar
• Matin S, Jahromi MG, Karemizadeh Z, et al. The frequency of adrenal insufficiency in adolescents and young adults with thalassemia major versus thalassemia intermedia in Iran. Mediterr J Hematol Infect Dis. 2015;7(1):e2015005.
   PubMedGoogle Scholar
• Huang KE, Mittelman SD, Coates TD, et al. A significant proportion of thalassemia major patients have adrenal insufficiency detectable on provocative testing. J Pediatr Hematol Oncol. 2015 Jan;37(1):54–59.
   PubMed Web of Science ®Google Scholar
• Costin G, Kogut MD, Hyman CB, et al. Endocrine abnormalities in thalassemia major. Am J Dis Child. 1979 May;133(5):497–502.
   PubMedGoogle Scholar
• el-Hazmi MA, Warsy AS, al-Fawaz I. Iron-endocrine pattern in patients with beta-thalassaemia. J Trop Pediatr. 1994 Aug;40(4):219–224.
   PubMed Web of Science ®Google Scholar
• Poomthavorn P, Isaradisaikul B, Chuansumrit A, et al. High prevalence of “biochemical” adrenal insufficiency in thalassemics: is it a matter of different testings or decreased cortisol binding globulin? J Clin Endocrinol Metab. 2010 Oct;95(10):4609–4615.
   PubMed Web of Science ®Google Scholar
• Jaruratanasirikul S, Tanchotikul S, Wongcharnchailert M, et al. A low dose adrenocorticotropin test (1 microg ACTH) for the evaluation of adrenal function in children with beta-thalassemia receiving hypertransfusion with suboptimal iron-chelating therapy. J Pediatr Endocrinol Metab. 2007 Nov;20(11):1183–1188.
   PubMed Web of Science ®Google Scholar
• Scacchi M, Danesi L, Cattaneo A, et al. The pituitary-adrenal axis in adult thalassaemic patients. Eur J Endocrinol. 2010 Jan;162(1):43–48.
   PubMed Web of Science ®Google Scholar
• Guzelbey T, Gurses B, Ozturk E, et al. Evaluation of iron deposition in the adrenal glands of beta thalassemia major patients using 3-Tesla MRI. Iran J Radiol. 2016 Jul;13(3):e36375.
   PubMed Web of Science ®Google Scholar
• Christoforidis A, Haritandi A, Tsitouridis I, et al. Correlative study of iron accumulation in liver, myocardium, and pituitary assessed with MRI in young thalassemic patients. J Pediatr Hematol Oncol. 2006 May;28(5):311–315.
   PubMed Web of Science ®Google Scholar
• Ambrogio AG, Danesi L, Baldini M, et al. Low-dose Synachten test with measurement of salivary cortisol in adult patients with beta-thalassemia major. Endocrine. 2018 May;60(2):348–354.
   PubMed Web of Science ®Google Scholar
• Baldini M, Mancarella M, Cassinerio E, et al. Adrenal insufficiency: an emerging challenge in thalassemia? Am J Hematol. 2017 Jun;92(6):E119–E121.
   PubMed Web of Science ®Google Scholar
• Vogiatzi MG, Macklin EA, Fung EB, et al. Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res. 2009 Mar;24(3):543–557.
   PubMed Web of Science ®Google Scholar
• Baldini M, Forti S, Marcon A, et al. Endocrine and bone disease in appropriately treated adult patients with beta-thalassemia major. Ann Hematol. 2010 Dec;89(12):1207–1213.
   PubMed Web of Science ®Google Scholar
• Shamshirsaz AA, Bekheirnia MR, Kamgar M, et al. Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. BMC Endocr Disord. 2003 Aug 12;3(1):4.
   PubMedGoogle Scholar
• Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Multicentre study on prevalence of endocrine complications in thalassaemia major. Clin Endocrinol (Oxf). 1995 Jun;42(6):581–586.
   PubMed Web of Science ®Google Scholar
• Wonke B. Bone disease in beta-thalassaemia major. Br J Haematol. 1998 Dec;103(4):897–901.
   PubMed Web of Science ®Google Scholar
• Morabito N, Russo GT, Gaudio A, et al. The “lively” cytokines network in beta-thalassemia major-related osteoporosis. Bone. 2007 Jun;40(6):1588–1594.
   PubMed Web of Science ®Google Scholar
• Bordat C, Constans A, Bouet O, et al. Iron distribution in thalassemic bone by energy-loss spectroscopy and electron spectroscopic imaging. Calcif Tissue Int. 1993 Jul;53(1):29–37.
   PubMed Web of Science ®Google Scholar
• Voskaridou E, Terpos E. New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia. Br J Haematol. 2004 Oct;127(2):127–139.
   PubMed Web of Science ®Google Scholar
• Bouillon R, Van Schoor NM, Gielen E, et al. Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. J Clin Endocrinol Metab. 2013 Aug;98(8):E1283–304.
   PubMed Web of Science ®Google Scholar
• Dandona P, Menon RK, Houlder S, et al. Serum 1,25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major. Arch Dis Child. 1987 May;62(5):474–477.
   PubMed Web of Science ®Google Scholar
• Moreira Guimaraes Penido MG, de Sousa Tavares M. Bone disease in pediatric idiopathic hypercalciuria. World J Nephrol. 2012 Apr 6;1(2):54–62.
   PubMedGoogle Scholar
• De Sanctis V, Soliman AT, Elsefdy H, et al. Bone disease in beta thalassemia patients: past, present and future perspectives. Metabolism. 2018 Mar;80:66–79.
   PubMed Web of Science ®Google Scholar
• Lasco A, Morabito N, Gaudio A, et al. Effects of hormonal replacement therapy on bone metabolism in young adults with beta-thalassemia major. Osteoporos Int. 2001;12(7):570–575.
   PubMed Web of Science ®Google Scholar
• Bousson V, Bergot C, Sutter B, et al. Trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects. Osteoporos Int. 2012 May;23(5):1489–1501.
   PubMed Web of Science ®Google Scholar
• Hans D, Goertzen AL, Krieg MA, et al. Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res. 2011 Nov;26(11):2762–2769.
   PubMed Web of Science ®Google Scholar
• Baldini M, Ulivieri FM, Forti S, et al. Spine bone texture assessed by trabecular bone score (TBS) to evaluate bone health in thalassemia major. Calcif Tissue Int. 2014 Dec;95(6):540–546.
   PubMed Web of Science ®Google Scholar
• Fung EB, Aguilar C, Micaily I, et al. Treatment of vitamin D deficiency in transfusion-dependent thalassemia. Am J Hematol. 2011 Oct;86(10):871–873.
   PubMed Web of Science ®Google Scholar
• Voskaridou E, Terpos E, Spina G, et al. Pamidronate is an effective treatment for osteoporosis in patients with beta-thalassaemia. Br J Haematol. 2003 Nov;123(4):730–737.
   PubMed Web of Science ®Google Scholar
• Voskaridou E, Anagnostopoulos A, Konstantopoulos K, et al. Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized, placebo-controlled trial. Haematologica. 2006 Sep;91(9):1193–1202.
   PubMed Web of Science ®Google Scholar
• Forni GL, Perrotta S, Giusti A, et al. Neridronate improves bone mineral density and reduces back pain in beta-thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel-arm, open-label study. Br J Haematol. 2012 Jul;158(2):274–282.
   PubMed Web of Science ®Google Scholar
• Yassin MA, Soliman AT, De Sanctis V, et al. Effects of the anti-receptor activator of nuclear factor kappa B ligand denusomab on beta thalassemia major-induced osteoporosis. Indian J Endocrinol Metab. 2014 Jul;18(4):546–551.
   PubMedGoogle Scholar
• Trotta A, Corrado A, Cantatore FP. Anabolic therapy of induced osteoporosis in beta-thalassaemia major: case report and literature review. Reumatismo. 2010 Apr-Jun;62(2): 119–126.
   PubMedGoogle Scholar
• Chung WS, Lin CL, Lin CL, et al. Thalassaemia and risk of cancer: a population-based cohort study. J Epidemiol Community Health. 2015 Nov;69(11):1066–1070.
   PubMed Web of Science ®Google Scholar
• Mancuso A. Hepatocellular carcinoma in thalassemia: A critical review. World J Hepatol. 2010 May 27;2(5):171–174.
   PubMedGoogle Scholar
• Fargion S, Valenti L, Fracanzani AL. Role of iron in hepatocellular carcinoma. Clin Liver Dis (Hoboken). 2014 May;3(5):108–110.
   PubMedGoogle Scholar
• Borgna-Pignatti C, Vergine G, Lombardo T, et al. Hepatocellular carcinoma in the thalassaemia syndromes. Br J Haematol. 2004 Jan;124(1):114–117.
   PubMed Web of Science ®Google Scholar
• Borgna-Pignatti C, Garani MC, Forni GL, et al. Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry. Br J Haematol. 2014 Oct;167(1):121–126.
   PubMed Web of Science ®Google Scholar
• Wirth TC, Manns MP. The impact of the revolution in hepatitis C treatment on hepatocellular carcinoma. Ann Oncol. 2016 Aug;27(8):1467–1474.
   PubMed Web of Science ®Google Scholar
• Origa R, Ponti ML, Filosa A, et al. Treatment of hepatitis C virus infection with direct-acting antiviral drugs is safe and effective in patients with hemoglobinopathies. Am J Hematol. 2017 Dec;92(12):1349–1355.
   PubMed Web of Science ®Google Scholar
• European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018 Aug;69(2):461–511.
   PubMed Web of Science ®Google Scholar
• Maakaron JE, Cappellini MD, Graziadei G, et al. Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia: a closer look at the role of siderosis. Ann Hepatol. 2013 Jan-Feb;12(1):142–146.
   PubMed Web of Science ®Google Scholar
• Moukhadder HM, Halawi R, Cappellini MD, et al. Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: A comprehensive review. Cancer. 2017 Mar 1;123(5):751–758.
   PubMed Web of Science ®Google Scholar
• Hodroj MH, Bou-Fakhredin R, Nour-Eldine W, et al. Thalassemia and malignancy: an emerging concern? Blood Rev. 2019 Jun 22;37:100585.
   PubMed Web of Science ®Google Scholar
• Poggi M, Sorrentino F, Pascucci C, et al. Malignancies in beta-thalassemia patients: first description of two cases of thyroid cancer and review of the literature. Hemoglobin. 2011;35(4):439–446.
   PubMed Web of Science ®Google Scholar
• De Sanctis V, Campisi S, Fiscina B, et al. Papillary thyroid microcarcinoma in thalassaemia: an emerging concern for physicians?. Georgian Med News. 2012 Sep;(210):71–76.
   PubMedGoogle Scholar
• Govoni MR, Sprocati M, Fabbri E, et al. Papillary thyroid cancer in thalassaemia. Pediatr Endocrinol Rev. 2011 Mar;8(Suppl 2):314–321.
   PubMedGoogle Scholar
• Ricchi P, Ammirabile M, Spasiano A, et al. Renal cell carcinoma in adult patients with thalassaemia major: a description of three cases. Br J Haematol. 2014 Jun;165(6):887–888.
   PubMed Web of Science ®Google Scholar
• Voskaridou E, Terpos E, Komninaka V, et al. Chronic myeloid leukaemia with marked thrombocytosis in a patient with thalassaemia major: complete haematological remission under the combination of hydroxyurea and anagrelide. Br J Haematol. 2002 Jan;116(1):155–157.
   PubMed Web of Science ®Google Scholar
• Schiliro G, Russo A, Marino S, et al. Occurrence of lymphoma with bone marrow involvement in a boy with beta+ thalassaemia major. Clin Lab Haematol. 1979;1(4):325–328.
   PubMedGoogle Scholar
• Otrock ZK, Shamseddine AI, Taher AT. Non-Hodgkin disease in beta-thalassemia major. Am J Hematol. 2006 Jan;81(1):62–64.
   PubMed Web of Science ®Google Scholar
• Jabr FI, Aoun E, Yassine H, et al. Beta-thalassemia intermedia and Hodgkin lymphoma. Am J Hematol. 2006 Feb;81(2):151.
   PubMed Web of Science ®Google Scholar
• Alavi S, Safari A, Sadeghi E, et al. Hematological malignancies complicating beta-thalassemia syndromes: a single center experience. Blood Res. 2013 Jun;48(2):149–151.
   PubMedGoogle Scholar
• Halawi R, Beydoun H, Cappellini MD, et al. Hematologic malignancies in thalassemia: adding new cases to the repertoire. Am J Hematol. 2017 May;92(5):E68–E70.
   PubMed Web of Science ®Google Scholar
• Hershko C. Pathogenesis and management of iron toxicity in thalassemia. Ann N Y Acad Sci. 2010 Aug;1202:1–9.
   PubMed Web of Science ®Google Scholar
• Porter JB, de Witte T, Cappellini MD, et al. New insights into transfusion-related iron toxicity: implications for the oncologist. Crit Rev Oncol Hematol. 2016;99:261–271.
   PubMed Web of Science ®Google Scholar
• Hoeks M, Yu G, Langemeijer S, et al. Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry. Haematologica. 2019 Jul 5. pii: haematol.2018.212332. DOI:10.3324/haematol.2018.212332. [Epub ahead of print].
   Web of Science ®Google Scholar
• Halawi R, Cappellini MD, Taher A. A higher prevalence of hematologic malignancies in patients with thalassemia: background and culprits. Am J Hematol. 2017 May;92(5):414–416.
   PubMed Web of Science ®Google Scholar
• Walker EM Jr., Walker SM. Effects of iron overload on the immune system. Ann Clin Lab Sci. 2000 Oct;30(4):354–365.
   PubMed Web of Science ®Google Scholar
• Sumboonnanonda A, Malasit P, Tanphaichitr VS, et al. Renal tubular function in beta-thalassemia. Pediatr Nephrol. 1998 May;12(4):280–283.
   PubMed Web of Science ®Google Scholar
• Ponticelli C, Musallam KM, Cianciulli P, et al. Renal complications in transfusion-dependent beta thalassaemia. Blood Rev. 2010 Nov;24(6):239–244.
   PubMed Web of Science ®Google Scholar
• Sumboonnanonda A, Sanpakit K, Piyaphanee N. Renal tubule function in beta-thalassemia after hematopoietic stem cell transplantation. Pediatr Nephrol. 2009 Jan;24(1):183–187.
   PubMed Web of Science ®Google Scholar
• Musallam KM, Taher AT. Mechanisms of renal disease in beta-thalassemia. J Am Soc Nephrol. 2012 Aug;23(8):1299–1302.
   PubMed Web of Science ®Google Scholar
• Koliakos G, Papachristou F, Koussi A, et al. Urine biochemical markers of early renal dysfunction are associated with iron overload in beta-thalassaemia. Clin Lab Haematol. 2003 Apr;25(2):105–109.
   PubMedGoogle Scholar
• Quinn CT, Johnson VL, Kim HY, et al. Renal dysfunction in patients with thalassaemia. Br J Haematol. 2011 Apr;153(1):111–117.
   PubMed Web of Science ®Google Scholar
• Diaz-Garcia JD, Gallegos-Villalobos A, Gonzalez-Espinoza L, et al. Deferasirox nephrotoxicity-the knowns and unknowns. Nat Rev Nephrol. 2014 Oct;10(10):574–586.
   PubMed Web of Science ®Google Scholar
• Agency EM. Exjade - SUMMARY OF PRODUCT CHARACTERISTICS. [cited 2019 Oct 18]. Available from: https://www.ema.europa.eu/en/documents/product-information/exjade-epar-product-information_en.pdf
   Google Scholar
• Administration USFaD. 2006. [cited 2019 Oct 18]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021882_s000_ExjadeTOC.cfm
   Google Scholar
• Yii E, Doery JC, Kaplan Z, et al. Use of deferasirox (Exjade) for iron overload in peritoneal dialysis patients. Nephrology (Carlton). 2018 Sep;23(9):887–889.
   PubMed Web of Science ®Google Scholar
• Beydoun HG, Saliba AN, Taher AT. Deferasirox in thalassemia patients with end-stage renal disease. Am J Hematol. 2016 Oct;91(10):E456–7.
   PubMed Web of Science ®Google Scholar
• Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006 May 1;107(9):3455–3462.
   PubMed Web of Science ®Google Scholar
• Origa R, Piga A, Tartaglione I, et al. Renal safety under long-course deferasirox therapy in iron overloaded transfusion-dependent beta-thalassemia and other anemias. Am J Hematol. 2018 Jul;93(7):E172–E175.
   PubMed Web of Science ®Google Scholar
• Efthimia V, Neokleous N, Agapidou A, et al. Nephrolithiasis in beta thalassemia major patients treated with deferasirox: an advent or an adverse event? A single Greek center experience. Ann Hematol. 2013 Jan;92(2):263–265.
   PubMed Web of Science ®Google Scholar
• Dede AD, Trovas G, Chronopoulos E, et al. Thalassemia-associated osteoporosis: a systematic review on treatment and brief overview of the disease. Osteoporos Int. 2016 Dec;27(12):3409–3425.
   PubMed Web of Science ®Google Scholar
• Morton A. A role for thiazide diuretic therapy in preventing bone loss, fracture, and nephrolithiasis in individuals with thalassemia and hypercalciuria? Osteoporos Int. 2017 May;28(5):1759.
   PubMed Web of Science ®Google Scholar