TY - JOUR
T1 - Primary HBB gene mutation severity and long-term outcomes in a global cohort of β-thalassaemia
AU - the International Working Group on Thalassemia (IWG-THAL)
AU - Musallam, Khaled M.
AU - Vitrano, Angela
AU - Meloni, Antonella
AU - Addario Pollina, Sebastiano
AU - Di Marco, Vito
AU - Hussain Ansari, Saqib
AU - Filosa, Aldo
AU - Ricchi, Paolo
AU - Ceci, Adriana
AU - Daar, Shahina
AU - Vlachaki, Efthymia
AU - Singer, Sylvia T.
AU - Naserullah, Zaki A.
AU - Pepe, Alessia
AU - Scondotto, Salvatore
AU - Dardanoni, Gabriella
AU - Karimi, Mehran
AU - El-Beshlawy, Amal
AU - Hajipour, Mahmoud
AU - Bonifazi, Fedele
AU - Vichinsky, Elliott
AU - Taher, Ali T.
AU - Sankaran, Vijay G.
AU - Maggio, Aurelio
N1 - Publisher Copyright:
© 2021 British Society for Haematology and John Wiley & Sons Ltd
PY - 2022/1
Y1 - 2022/1
N2 - In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β0/β0, β0/β+, β+/β+, β0/β++, β+/β++, and β++/β++. Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β0 and β+ mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with β0/β0, β0/β+, or β+/β+ had a 2·104-increased risk of death [95% confidence interval (CI): 1·176–3·763, P = 0·011] and 2·956-increased odds of multiple morbidity (95% CI: 2·310–3·784, P < 0·001) compared to patients in lower genotype severity groups. Cumulative survival estimates by age 65 years were 36·8% for this subgroup compared with 90·2% for patients in lower genotype severity groups (P < 0·001). Our study identified mortality and morbidity risk estimates across various genotype severity groups in patients with β-thalassaemia and suggests inclusion of both β+ and β0 mutations in strata of greatest severity.
AB - In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β0/β0, β0/β+, β+/β+, β0/β++, β+/β++, and β++/β++. Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β0 and β+ mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with β0/β0, β0/β+, or β+/β+ had a 2·104-increased risk of death [95% confidence interval (CI): 1·176–3·763, P = 0·011] and 2·956-increased odds of multiple morbidity (95% CI: 2·310–3·784, P < 0·001) compared to patients in lower genotype severity groups. Cumulative survival estimates by age 65 years were 36·8% for this subgroup compared with 90·2% for patients in lower genotype severity groups (P < 0·001). Our study identified mortality and morbidity risk estimates across various genotype severity groups in patients with β-thalassaemia and suggests inclusion of both β+ and β0 mutations in strata of greatest severity.
UR - http://www.scopus.com/inward/record.url?scp=85117957604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117957604&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/622e4d1b-774d-3696-b9e8-922b61102e53/
U2 - 10.1111/bjh.17897
DO - 10.1111/bjh.17897
M3 - Article
C2 - 34697800
AN - SCOPUS:85117957604
SN - 0007-1048
VL - 196
SP - 414
EP - 423
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 2
ER -