A complication risk score to evaluate clinical severity of thalassaemia syndromes Angela Vitrano, 1 Antonella Meloni, 2 Walter Addario Pollina, 3 Mehran Karimi, 4 Amal El-Beshlawy, 5 Mahmoud Hajipour, 6 Vito Di Marco, 7 Saqib Hussain Ansari, 8 Aldo Filosa, 9 Paolo Ricchi, 9 Adriana Ceci, 10 Shahina Daar, 11,12 Sylvia Titi Singer, 13 Zaki A. Naserullah, 14 Alessia Pepe, 2 Salvatore Scondotto, 3 Gabriella Dardanoni, 3 Fedele Bonifazi, 10 Elliott Vichinsky 13 and Aurelio Maggio 1 1 Campus of Haematology Franco and Piera Cutino, AOOR Villa Sofia-V. Cervello, 2 U.O.C. MRI, Fondazione Toscana G. Monasterio, Pisa, 3 D.A.S.O.E, Regione Siciliana, 4 Haematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, 5 Cairo University, Giza, Egypt, 6 Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 7 Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy, 8 Department of Paediatric Haematology and Molecular Medicine, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, 9 Rare Blood Cell Disease Unit, "Cardarelli" Hospital, Naples, 10 Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus, Valenzano, BA, Italy, 11 Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman, 12 Wallenberg Research Centre, Stellenbosch Institute for Advanced Study, Stellenbosch University, Stellenbosch, South Africa, 13 Haematology/Oncology Department, Oakland, CA, USA, and 14 Dammam Maternity and Child Hospital, Dammam, Saudi Arabia Abstract The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complica- tions. Nine independent variables were included in the inves- tigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non- transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminases [ala- nine aminotransferase (ALT) and aspartate aminotransferase] and left-ventricular ejection fraction (LVEF) for Group A; age (years), age at first chelation (months), ALT and LVEF for Group B; and age (years), mean serum ferritin (SF) levels and LVEF for Group C. The area under the receiver operat- ing characteristic curve was 84Á5%, 82Á1% and 80Á0% for Groups A, Group B and Group C respectively, suggesting the models had good discrimination. Finally, the CoRS for each group was categorised into four risk classes (low, intermedi- ate, high, and very high) using the centiles of its distribution. In conclusion, we have developed a CoRS for TS that can assist physicians in prospectively tailoring patients’ treatment. Keywords: thalassaemia, prognostic model, complications, risk score. Introduction The thalassaemia syndromes (TS) are recessively inherited disorders of haemoglobin synthesis resulting from a hetero- geneous group of mutations in the b-globin gene and defec- tive b-globin chain production. 1,2 An estimated 1–5% of the global population are carriers of a genetic thalassaemia muta- tion. 3,4 Although the epidemiology of the various clinical forms remains poorly recognised, the disease is known to be highly prevalent in the area extending from sub-Saharan Africa, through the Mediterranean region and Middle East, to the Indian subcontinent and East and Southeast Asia. 5 Thus, >90% of patients with these disorders live in low- and middle-income countries. The hallmark of the disease pro- cess, with or without treatment, in homozygous or com- pound heterozygous patients is characterised by an imbalance in the a/b-globin chain ratio, ineffective erythro- poiesis and an array of subsequent pathophysiological mech- anisms leading to variable degrees of chronic anaemia, transfusion requirement and a multi-morbidity profile. 6,7 Current classification of TS is primarily based on expert opinion. Three main clinical groups are recognised: heterozy- gote state or thalassaemia minor, non-transfusion-dependent Correspondence: Prof. Aurelio Maggio, Campus of Haematology Franco and Piera Cutino, AOOR Villa Sofia-V. Cervello, Palermo, Italy. E-mail: md.amaggio@gmail.com research paper ª 2020 British Society for Haematology and John Wiley & Sons Ltd doi: 10.1111/bjh.17203