Development of a Thalassemia International Prognostic Scoring System (TIPSS).

A prognostic scoring system that can differentiate β-thalassemia patients based on mortality risk is lacking. We analysed data from 3145 β-thalassemia patients followed through a retrospective cohort design for the outcome of death. An a priori list of prognostic variables was collected. β Coefficients from a multivariate cox regression model were used from a development dataset (n = 2516) to construct a formula for a Thalassemia International Prognostic Scoring System (TIPSS) which was subsequently applied to a validation dataset (n = 629). The median duration of observation was 10.0 years. The TIPSS score formula was constructed as exp (1.4 × heart disease + 0.9 × liver disease + 0.9 × diabetes + 0.9 × sepsis + 0.6 × alanine aminotransferase ≥42 IU/L + 0.6 × hemoglobin ≤9 g/dL + 0.4 × serum ferritin ≥1850 ng/mL). TIPSS score thresholds of greatest differentiation were assigned as <2.0 (low-risk), 2.0 to <5.0 (intermediate-risk), and ≥5.0 (high-risk). The TIPSS score was a good predictor for the outcome of death in the validation dataset (AUC: 0.722, 95%CI: 0.641-0.804) and survival was significantly different between patients in the three risk categories (P < 0.001). Compared to low-risk patients, the hazard ratio for death was 2.778 (95%CI: 1.335-5.780) in patients with intermediate-risk and 6.431 (95%CI: 3.151-13.128) in patients with high-risk. This study provides a novel tool to support mortality risk categorization for patients with β-thalassemia that could help management and research decisions.
Competing Interests: Declaration of competing interest Khaled M. Musallam has been or is a consultant for Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, CRISPR Therapeutics and Vifor Pharma. Efthymia Vlachaki received hononaria from DEMO S.A. Pharmaceutical Industry and Novartis. Alessia Pepe is the principal investigator of the MIOT project that receives ‘non-profit support’ from industrial sponsorships (Chiesi Farmaceutici S.p.A. and Bayer) and she received speakers' honoraria from Chiesi Farmaceutici S.p.A. Ali T. Taher has been or is consultant for Novartis, Celgene Corp (Bristol Myers Squibb), Vifor Pharma, Silence Therapeutics and Ionis Pharmaceuticals; and received research funding from Novartis, Celgene Corp (Bristol Myers Squibb), La Jolla Pharmaceutical Company, Roche, Protagonist Therapeutics and Agios Pharmaceuticals. Vijay G Sankaran serves as an advisor to and/or has equity in Novartis, Forma, Cellarity, Ensoma, and Branch Biosciences. Aurelio Maggio has been or is a member of advisory boards for Novartis, Celgene Corp (Bristol Meyers Squibb) and Bluebird Bio. The remaining authors have no conflicts of interest to disclose.
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