P1452: mortality and clinical complications among patients with transfusion-dependent beta-thalassemia in italy

Topic: 27. Thalassemias Background: β-thalassemia is a rare hereditary disorder characterized by reduced or absent β-globin production. The most severe form of the disease is transfusion-dependent β-thalassemia (TDT), in which patients require regular red blood cell transfusions (RBCTs) and iron chelation therapies (ICTs) for survival. Individuals with TDT experience significant clinical complications associated with ineffective erythropoiesis, hemolysis, and iron overload that can lead to early mortality. Aims: To describe the mortality and clinical complications among patients with TDT in Italy. Methods: This longitudinal, retrospective cohort study utilized a database of Italian local health units covering 12 million Italian national health service-health assisted individuals to identify patients with ≥8 RBCTs over a 12-month period and ≥1 ICT prescription between January 1, 2011, and February 1, 2019 (eligibility period). Patients with myelodysplastic syndrome, myelofibrosis, iron deficiency anemia, congenital anemias, or myelophthisis were excluded from the analysis. Patients who had received a hematopoietic stem cell transplant or had been prescribed erythropoietin were also excluded from the analysis. The index date was the first transfusion of the ≥8 RBCTs in any 12-month period during the eligibility period. Eligible patients were required to be continuously enrolled for 1 year before and after their index date. Each patient was matched to 5 controls without disease by age, geographic area, gender, and index year. Patients and controls were followed from index until death, exiting the database, or end of study period (February 1, 2020), whichever occurred first. Demographics were assessed at index. Mortality (proportion of total population and rate [deaths per 100 person-years]) was summarized for patients and controls, and a chi-squared test was used for significance testing (P<0.05) for mortality rate differences. Clinical complications (proportion of total population) were summarized descriptively during follow-up for patients with TDT. Results: In total, 214 patients with TDT met the inclusion criteria and were matched to 1,070 controls. The mean age of patients was 46.7 years, and 45.8% were male. Controls had similar demographics. Mortality proportion (Patients with TDT: 47/214 [22.0%] vs. controls: 48/1,070 [4.5%]) and rate per 100 person-years (4.8 vs. 0.8; P<0.001, respectively) were higher for patients with TDT than for matched controls. The most prevalent complications in patients with TDT were endocrine complications (19.2%), liver complications (14.5%), malignancies (13.1%), cardiopulmonary complications (12.1%), and musculoskeletal complications (10.3%). Summary/Conclusion: Patients with TDT had significantly higher mortality than the matched general population. Despite the best available care, patients with TDT experience significant clinical complications associated with the disease, highlighting the need for innovative therapies in this space. Keywords: beta thalassemia, Hemoglobinopathy, Complications, Mortality