Background Acquired aplastic anemia is a rare, life-threatening hematologic disorder characterized by immune-mediated bone marrow failure. Despite therapeutic advancements that have increased survival, evaluating contemporary mortality trends in the United States remains important to inform clinical practice and health policy. Objectives This study examined aplastic anemia-related mortality trends, demographic disparities, and geographic variation among United States adults from 1999 to 2020. Methods Death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database were analyzed for adults aged 25 years and older. Age-adjusted mortality rates per 100,000 persons and annual percent changes were calculated across years, sex, race, ethnicity, and geographic regions. Place of death and state-level social vulnerability index correlations were also evaluated. Results Aplastic anemia was recorded in 107,975 deaths from 1999 to 2020. The national age-adjusted mortality rate decreased initially from 1999 to 2002, remained stable until 2015, and increased through 2020. Men consistently demonstrated higher age-adjusted mortality rates than women. Non-Hispanic Black or African American individuals had the highest mortality rates among racial groups. Mortality was higher in non-metropolitan areas and the Midwest region. Mortality varied widely across states, whereas state-level social vulnerability was not associated with mortality rates. Conclusions Following a period of stability, aplastic anemia-related mortality has increased in the United States since 2015. Disparities persist across sex, race, urbanization, and geographical region.
Background Primary immune thrombocytopenia requires diagnostic exclusion and individualized management. Recent changes in the therapeutic landscape and health technology assessment recommendations of Brazil prompted an update of the national Clinical Practice Guidelines for immune thrombocytopenia in the Unified Health System (SUS). Objectives This study aims to describe the methodological process used to update the guidelines for primary immune thrombocytopenia, summarize the primary conceptual, diagnostic, and therapeutic updates, and emphasize the integration of health technology assessment into treatment pathways within the Brazilian Unified Health System. Methods The update followed the technical guide of the Brazilian Ministry of Health for guideline development. Recommendations were appraised by the National Committee for Health Technology Incorporation (Conitec) and drafted by a multidisciplinary panel including health technology assessment researchers, clinical experts and policymakers. Systematic reviews, economic evaluations, budget impact analyses, stakeholder input and public consultation drafted the final recommendations. Results The updated Clinical Practice Guidelines changed the title and conceptual framing to reflect contemporary disease nomenclature and immune‑mediated pathophysiology, reinforced a diagnostic approach based on clinical evaluation and exclusion of alternative causes of thrombocytopenia, and reorganized classification criteria. Rituximab and romiplostim were incorporated for selected adult and pediatric populations with refractory, chronic or corticosteroid‑dependent disease, whereas dapsone was not incorporated. Treatment sequencing was clarified, positioning immunosuppressive therapies before thrombopoietin receptor agonists and specifying age‑related indications. A public consultation refined the wording and interpretation of the therapeutic sequencing, particularly for pediatric care. Conclusion The updated Brazilian Clinical Practice Guidelines for primary immune thrombocytopenia modernizes disease framing, expands treatment options and improves organization of therapeutic decision‑making in the Unified Health System (SUS), illustrating how health technology assessment outputs can be integrated into evidence‑informed national clinical protocols.
Background: The METER study (NCT05444972) described real-world treatment patterns and outcomes for myelofibrosis across 14 countries. Given the potential regional variability, the present analysis evaluates the Brazilian cohort within METER to investigate local treatment approaches and patient results. Methods: This subanalysis of the METER study included all patients enrolled in Brazil, based on the same eligibility criteria as in the global study. The primary objective was to describe real-world treatment patterns for myelofibrosis. Main results: Of 50 eligible patients enrolled in Brazil, 37 (74%) presented with primary myelofibrosis. At diagnosis, nine (20.9%) individuals had high-risk and 14 (32.6%) intermediate-2 risk disease, mostly using the Dynamic International Prognostic Scoring System (DIPSS) criteria. Among patients with available data (n = 18), 50% had a high-risk mutation at diagnosis. Hydroxyurea was the most frequent initial therapy (n = 32; 64%), followed by ruxolitinib (n = 12; 24%). A total of 23 patients (46%) had discontinuation or change of initial therapy, with a median overall duration of first-line treatment of 29.9 months (95% confidence interval: 21.5 to not estimable). The median overall survival from index date was 45.5 months (95% confidence interval: 28.5 to not estimable), with 1- and 2-year survival rates of 87.3% and 74.7%, respectively. Conclusion: The treatment patterns in Brazil reflect insufficient access to novel agents. Whether the shorter observed median overall survival compared with the overall METER study is a consequence of insufficient access to treatment or of different biological features warrants further investigation.
Background Chimeric Antigen Receptor T-cell (CAR T-cell) therapy is a promising treatment option for patients with refractory or relapsed B-cell malignancies. The success of this therapy depends on the efficient collection of lymphocytes (CD3+ T cells) through apheresis. This study analyzed the factors influencing CD3+ cell counts in apheresis products for CAR T-cell therapy. Methods This exploratory analysis evaluated patients enrolled in the registration phase I/II trials of talicabtagene autoleucel at a tertiary care oncology centre in Western India. Patients were enrolled after obtaining informed consent. The study was approved by the Institutional Ethics Committee and the Central Drugs Standard Control Organisation (CDSCO), and registered with the Clinical Trials Registry of India. A total of 48 autologous lymphocytapheresis procedures were performed on 44 patients with refractory or relapsed lymphoma (predominantly diffuse large B-cell lymphoma) or B-acute lymphoblastic leukemia. Pre-apheresis hematological parameters and flow cytometry were used to estimate absolute lymphocyte counts and peripheral blood CD3+ cell counts. Predictive factors for CD3+ cells in the product were analyzed using the Pearson correlation coefficient and regression models by the Statistical Package for Social Sciences software (Version 25.0, Armonk, NY: IBM Corp.), and p-values <0.05 were considered statistically significant. Results Pre-apheresis parameters like total leukocyte count, absolute lymphocyte count, and circulating CD3⁺ cell count were all positively correlated with the absolute CD3+ cell yield in the apheresis product (p < 0.05). Importantly, these associations remained significant in multivariate analysis, highlighting their independent predictive value for the harvested CD3+ count. Additionally, lower pre-apheresis hematocrit and higher platelet levels were independently associated with reduced CD3+ recovery. Notably, the targeted CD3+ cell dose was successfully achieved in 96 % (46/48) of collections. Conclusion Pre-apheresis total leukocyte count, absolute lymphocyte counts, CD3+ cells, hematocrit, and platelet counts are key factors influencing the successful collection of CD3+ cells during apheresis. Understanding these variables is crucial for optimizing lymphocyte collection for CAR T-cell manufacturing.
