Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by biallelic SMN1 variants, partially modulated by SMN2 copy number. Risdiplam, an oral SMN2 splicing modifier, has demonstrated efficacy in SMA. However, long-term adherence and persistence are key to sustaining benefit. We evaluated real-world adherence, persistence, and safety of risdiplam in a population-based cohort. This was a retrospective observational study including all genetically confirmed SMA type 1–3 patients treated with risdiplam in Spain between January 2020 and October 2025. Adherence was assessed using the proportion of days covered (PDC) from pharmacy dispensing records and the Morisky–Green questionnaire. Persistence was defined as time to permanent discontinuation or switch. Adverse events (AEs) were extracted from clinical records, and Kaplan–Meier analysis was used to estimate persistence probabilities. Fifty-three patients were included (38 adults, 15 pediatric patients); 5.7
BACKGROUND:Hepatitis C virus (HCV) has significantly impacted people with human immunodeficiency virus (HIV). Harm reduction programs, changing transmission patterns, and direct-acting antivirals (DAAs) have profoundly altered HIV/HCV coinfection trends. This study evaluates HCV prevalence among people with HIV in Spain over 2 decades. METHODS:We conducted 9 cross-sectional studies (2002-2023) in 39-43 centers. Sampled individuals were randomly sampled from people with HIV actively followed up at these centers, with proportional allocation. Main outcomes included the prevalence of anti-HCV antibody and active HCV infection (HCV RNA--positive result). RESULTS:The reference population ranged from 31 800 to 47 006, with sample sizes of 1260-1867. HIV transmission patterns shifted from 2002 to 2023, with injection drug use decreasing from 55% to 21% and the proportion of men who have sex with men increasing from 17% to 46%. HCV seroprevalence fell from 60.8% to 27.4%, and active infection from 46.3% to 0.9%. In the DAA era (2015-2023), active HCV infection dropped by 100% in heterosexuals, 94% in people who inject drugs, and 71% in men who have sex with men. Treatment uptake increased from 23% in 2002 to 99% by 2023 with all-oral DAAs. The prevalence of cirrhosis among active HCV cases peaked at 23.1% in 2015 but fell to 0% by 2021. Among those achieving sustained virologic response, cirrhosis prevalence was 20.4% in 2023. CONCLUSIONS:HIV/HCV coinfection has drastically declined in Spain, with active HCV infection prevalence <1% since 2021. DAAs were pivotal in this achievement. However, cirrhosis remains a concern among those with sustained virologic response. Ongoing surveillance and prevention efforts are essential to sustain these gains and address residual risks.
ABSTRACT:QuANTUM-First was a randomized trial that demonstrated that the addition of quizartinib, a potent and selective FMS-like tyrosine kinase 3 (FLT3) inhibitor, to induction and consolidation chemotherapy, followed by monotherapy maintenance, improved the survival for patients with newly diagnosed FLT3-internal tandem duplication (FLT3-ITD)-mutated acute myeloid leukemia. We conducted a post hoc analysis of the trial data focusing on measurable residual disease (MRD) as assayed using an amplicon-based next-generation sequencing assay, and on the impact of molecular biomarkers such as FLT3-ITD insertion length and comutations. This is, to our knowledge, the first prospective, randomized trial of an FLT3 inhibitor in newly diagnosed patients in which FLT3-ITD MRD data were collected throughout therapy. We established that quizartinib induces deeper remissions with respect to FLT3-ITD MRD vs placebo, and that the amount of MRD at the completion of induction correlates with relapse and survival. We found that longer FLT3-ITD insertion mutations correlated with worse outcome, quizartinib was beneficial irrespective of insertion mutation length, and the FLT3-ITD MRD assay was more sensitive when bone marrow was used vs peripheral blood. Regardless of the presence of NPM1 (nucleophosmin 1) comutation, quizartinib increased the rates of MRD negativity at the end of induction vs placebo. Finally, comparison of the FLT3-ITD mutation length between the polymerase chain reaction (PCR) with capillary electrophoresis assay obtained at screening and the PCR next-generation sequencing MRD assay performed at the end of induction showed a 96.2% concordance with the exact ITD length. This trial was registered at www.clinicaltrials.gov as #NCT02668653.
Chronic graft-versus-host disease (cGVHD) remains a leading cause of late morbidity after allogeneic hematopoietic cell transplantation (HCT), but its phenotype under modern prophylaxis with post-transplant cyclophosphamide (PTCy) is not well characterized. We conducted a prospective, single-center study of 600 consecutive adults undergoing HCT with PTCy- based prophylaxis to assess incidence, clinical manifestations, treatment response, prognostic factors, and outcomes. Donors included matched siblings (36%), matched unrelated (34%), haploidentical (24%), and mismatched unrelated (6%). The 1-year cumulative incidence of moderate-to-severe cGVHD was 22% (95% confidence interval [CI]: 19-26%). The mouth was the most frequently involved organ (64%), with lichen planus-like changes as the predominant diagnostic feature, whereas sclerotic forms were uncommon. Notably, 27% of moderate-to-severe cases were managed successfully without systemic corticosteroids. The cumulative incidence of systemic therapy requirement was 15% at 1 year, with risk significantly higher in donors ≥30 years and in female-to-male transplants. Among 105 patients requiring systemic steroids, 64% achieved complete response, 32% discontinued immunosuppression, yet 18% developed cGVHD-related sequelae. Mouth ulcers and erythema, as well as a lung score ≥2 at steroid initiation independently predicted shorter failure-free survival. At 2 years, overall survival, cGVHD-free relapse-free survival, and GVHD-free relapse-free survival were 76% (95% CI: 72-79), 63% (95% CI: 60-68), and 57% (95% CI: 53-62), respectively. In conclusion, after HCT with PTCy-based prophylaxis, systemic therapy was required in only a minority of patients, with risk influenced by donor age and sex mismatch rather than donor type. While corticosteroids were generally effective, a substantial subset required salvage therapy, underscoring the burden of refractory cGVHD and the need for steroid-sparing approaches and novel interventions.
