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Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study

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Anuja P. Premawardhena, Dileepa Senajith Ediriweera, Amir Sabouhanian, Angela Allen, David Rees, Shanthimala de Silva, Windsor Perera, Nimal Katugaha, Mahinda Arambepola, Robert C. Yamashita, Sachith Mettananda, Nilam Jiffry, Vikita Mehta, Refai Cader, Dayananda Bandara, Timothy St Pierre, Giulia Muraca, Christopher Fisher, Abirami Kirubarajan, Shawn Khan & 4 more Stephen Allen, Sanath P. Lamabadusuriya, David J. Weatherall, Nancy F. Olivieri

Original languageEnglish
Pages (from-to)e134-e141
JournalThe Lancet Global Health
Volume10
Issue number1
DOIs
PublishedJan 2022

Bibliographical note

Funding Information: This study was supported by the Wellcome Trust (053267/Z98F), Medical Research Council (4050189188), US March of Dimes, the Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal. We wish to acknowledge the support rendered by the many medical officers, nursing officers, laboratory personnel, clinic volunteers, and support staff of the National Center, Kurunegala, Sri Lanka. We are grateful for the interest, support, and contributions of the patients and the families, both past and present, attending the National Center. We thank Martin Pippard for analysis of liver iron concentrations in liver biopsies. Funding Information: This study was supported by the Wellcome Trust (053267/Z98F), Medical Research Council (4050189188), US March of Dimes, the Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal. We wish to acknowledge the support rendered by the many medical officers, nursing officers, laboratory personnel, clinic volunteers, and support staff of the National Center, Kurunegala, Sri Lanka. We are grateful for the interest, support, and contributions of the patients and the families, both past and present, attending the National Center. We thank Martin Pippard for analysis of liver iron concentrations in liver biopsies. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

King's Authors

Abstract

Background: Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. Methods: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. Findings: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14–20). Median age at recruitment was 13 years (range 8–21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45–not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16–5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90–24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01–1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 μg/L (vs concentration ≤1300 μg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. Interpretation: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival. Funding: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

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