Myelodysplastic syndromes (MDS) remain underrepresented in epidemiologic research from Latin America. Large studies such as Belli et al. (2015) and the Re-GLAM registry (2022) provided important insights into the clinical and cytogenetic landscape of MDS in the region, with median overall survival (OS) ranging from 35 to 56 months. However, the impact of genomic drivers on outcomes in Latin American populations has remained largely unexplored. To date, no Brazilian cohort has comprehensively applied next-generation sequencing (NGS) combined with the 2022 World Health Organization/ International Consensus Classification (WHO/ICC) classifications, the International Prognostic Scoring System–Molecular (IPSS-M), and the recently proposed taxonomic classification by Bernard et al.(2024). The molecular perspective in MDS is an unmet epidemiological need and lacks region-specific data to refine risk stratification and therapeutic decision-making.

We conducted a retrospective single-center analysis of 114 patients with MDS diagnosed between January 2018 and December 2024 at a private tertiary hospital in Brazil. All patients underwent bone marrow evaluation, conventional cytogenetics, and comprehensive next-generation sequencing (NGS) of a myeloid gene panel. Cases were classified according to the 2022 WHO/ICC, and taxonomic classification. Risk was assessed using both IPSS-R and IPSS-M. Survival outcomes were estimated by Kaplan–Meier analysis, with subgroup comparisons by age, molecular alterations, and treatment modality, including hypomethylating agents (HMA), venetoclax, and allogeneic hematopoietic stem cell transplantation (HSCT).

The median age at diagnosis was 75 years (range, 33–95), significantly older than in prior Latin American cohorts, with a predominance of male patients (59.6%). According to 2022 WHO/ICC, the most common subtypes were MDS with low blasts (29.8%)/MDS with multilineage dysplasia (27,2%), MDS with SF3B1 mutation (14.9%/17,5%), MDS with increased blasts (21.1%)/MDS-EB or MDS/AML (26,3%). IPSS-R classified 48,2% as very low/low, 21.9% as intermediate, 36,8%as high/very high risk. In contrast, IPSS-M upstaged 18% of cases: 44,5% very low/low/intermediate-low, 55,5% intermediate-high/high/very high. By IPSS-R the prevalence of patients classified as high/very high risk was significantly higher than <25%that was reported in previous Latin American series. Applying molecular taxonomy, the most frequent categories were TP53-complex (21.2%), SF3B1 (15,1%). The most common mutations were SF3B1 (28.9%), TET2 (24.4%), ASXL1 (23.3%), and TP53 (16.7%). We identified a higher prevalence of patients in the TP53-complex (p=0,000159) and AML-like (p=0,27) subgroups compared with the pivotal study, suggesting that, at least in the Brazilian population with access to NGS panels, the disease tends to present at more advanced stages. Despite being predominantly a high-risk population, our cohort demonstrated survival curves comparable to those reported in the Latin American and international literature.

Median OS for the entire cohort was 50.4 months (95% CI, 37.2–not reached). Patients <70 years had significantly better outcomes (p=0.0029). TP53 mutations conferred poorest OS (p<0.0001), whereas SF3B1 did not yield a survival advantage (p=0.68). Venetoclax-based regimens were administered in 9% of the cohort and were associated with a trend toward improved OS (p=0.28). Among patients who underwent transplantation, median OS was not reached during follow-up, in sharp contrast to the median of 37.2 months observed in non-transplanted patients. These results confirm the curative potential of allogeneic transplantation in MDS, underscoring its role as the only strategy capable of durably altering the natural history of the disease.This is the first Brazilian cohort to systematically apply IPSS-M and molecular taxonomy. Despite a significantly older median age, overall survival was comparable to prior series. Our findings confirm the strong adverse prognostic impact of TP53-complex subgroups, emphasize the utility of IPSS-M in refining risk stratification, and validate the clinical relevance of the molecular taxonomy in Latin America. This study highlights the critical importance of routine molecular profiling in MDS and establishes a benchmark for future collaborations aimed at improving outcomes in underrepresented populations.

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2025
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