{ "abstract": "Introduction: Risk prediction in sickle cell disease (SCD) is commonly reported using hazard ratios, which are often difficult to interpret in clinical practice. Estimating the adjusted predicted life expectancy from parametric survival models may provide a more intuitive measure of prognosis and facilitate communication of disease burden to clinicians and patients. Objective: To estimate genotype-specific predicted life expectancy associated with major clinical risk factors in patients with SCD using standardized Weibull survival models. Methods: This longitudinal study included 2,696 participants from the Brazilian Recipient Epidemiology and Donor Evaluation Study III (REDS-III), a prospective multicenter cohort of patients with SCD, comprising 2,052 individuals with HbSS/HbSβ⁰ and 644 with HbSC disease. Parametric Weibull survival models accounting for left truncation were fitted separately for each genotype. For each prognostic factor, adjusted predicted life expectancy was estimated using marginal standardization by assigning all individuals to each exposure level while preserving the observed distribution of adjustment covariates. Confidence intervals were obtained by patient-level bootstrap resampling. Associations were assessed using likelihood ratio tests. Results: Among the 2,696 participants, sex distribution and age at enrollment were similar between HbSC and HbSS/HbSβ⁰ groups (54.2% vs. 52.7% female, p=0.516; mean age 20.7±15.8 vs. 20.0±13.2 years, p=0.330). However, HbSC participants were more frequently ≥40 years at enrollment (14.9% vs. 9.6%, p<0.001). Distinct genotype-specific prognostic profiles were identified. Among individuals with HbSS/HbSβ⁰, pulmonary hypertension was associated with the greatest reduction in adjusted predicted life expectancy, corresponding to nearly 10 fewer years of life (26.4 vs. 36.3 years; difference -9.9-years, 95% CI -15.5 to -4.1; p=0.003). Likewise, patients requiring >0.33 transfusions/year had a markedly shorter predicted life expectancy than those with a lower transfusion burden (30.2 vs. 41.1 years; difference -10.8-years, 95% CI -18.4 to -5.1; p<0.001). Acute chest syndrome and hospitalization burden (>1 hospitalization/year) showed non-significant trends toward lower reduced life expectancy, whereas hydroxyurea use was not associated with predicted age at death. In contrast, among HbSC patients, hydroxyurea use identified a subgroup with markedly lower adjusted predicted life expectancy (34.6 vs. 50.8 years; difference -16.3 years, 95% CI -38.1 to -1.7; p=0.029), while annual hospitalization burden and acute chest syndrome were not significantly associated with survival. Discussion and Conclusions: Expressing prognosis as predicted life expectancy rather than hazard ratios provides an intuitive and clinically meaningful measure of prognosis in SCD. Prognostic determinants differed substantially by genotype. In HbSS/HbSβ⁰ disease, with pulmonary hypertension and higher transfusion burden were associated with approximately 10 fewer years of predicted life, highlighting patients who may benefit from closer monitoring and earlier disease-modifying interventions. In HbSC disease, hydroxyurea use identified a higher-risk subgroup, likely reflecting treatment indication in patients with more severe disease. This approach translates complex survival models into clinically interpretable estimates that may improve patient counseling, individualized risk stratification, and clinical decision-making.", "abstract_shown": true, "affiliations": [ "Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil", "Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP, Brazil", "Universidade de São Paulo (USP), São Paulo, SP, Brazil", "Universidade Municipal de São Caetano do Sul (USCS), São Caetano do Sul, SP, Brazil", "Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope), Recife, PE, Brazil", "Fundação Hemorio, Rio de Janeiro, RJ, Brazil", "Fundação Hemominas, Juiz de Fora, MG, Brazil", "Vitalant Research Institute, United States" ], "article_type": null, "arxiv": null, "author_total": 13, "authors": [ { "affs": [ 0 ], "name": "Isabel Cristina Gomes MOURA" }, { "affs": [ 1 ], "name": "Carla Luana DINARDO" }, { "affs": [ 2 ], "name": "Mina Cintho OZAHATA" }, { "affs": [ 3 ], "name": "Sheila MATEOS" }, { "affs": [ 2 ], "name": "Márcio OIKAWA" }, { "affs": [ 4 ], "name": "Alessandra FERRAZ" }, { "affs": [ 5 ], "name": "Luiz AMORIM" }, { "affs": [ 6 ], "name": "André BELISáRIO" }, { "affs": [ 6 ], "name": "Anna Bárbara PROIETTI" }, { "affs": [ 7 ], "name": "Shannon KELLY" }, { "affs": [ 7 ], "name": "Brian CUSTER" }, { "affs": [ 2 ], "name": "Ester SABINO" }, { "affs": [ 1 ], "name": "Vanderson ROCHA" } ], "bibtex": "https://research.draconitic.com/paper/7zzdya78wa29w.bib", "cited_by": 0, "doi": "10.1016/j.htct.2026.106694", "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926004414", "id": "7zzdya78wa29w", "issns": [ "2531-1379", "2531-1387" ], "landing_url": "https://doi.org/10.1016/j.htct.2026.106694", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC633-647.5" ], [ "openalex", "2716|Hemoglobinopathies and Related Disorders" ] ], "openalex": "W7223149921", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "Elsevier", "ris": "https://research.draconitic.com/paper/7zzdya78wa29w.ris", "sources": [ { "first_seen": "2026-10-30T13:43:27Z", "native_id": "9f51a784778640168dabc6b35e2debc3", "source": "doaj", "url": "https://doi.org/10.1016/j.htct.2026.106694" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2716|Hemoglobinopathies and Related Disorders", "subfield": "human-genetics" } ], "title": "PREDICTED LIFE EXPECTANCY IMPROVES CLINICAL INTERPRETATION OF SURVIVAL MODELS IN SICKLE CELL DISEASE", "title_text": "PREDICTED LIFE EXPECTANCY IMPROVES CLINICAL INTERPRETATION OF SURVIVAL MODELS IN SICKLE CELL DISEASE", "type": "peer-reviewed", "updated_at": "2026-10-30T13:43:27Z", "url": "https://research.draconitic.com/paper/7zzdya78wa29w", "venue": "Hematology, Transfusion and Cell Therapy", "versions": [] }