Understanding Progression in MDS: Insights From the Prospective MDS Natural History Study

By Blood Cancers Today Staff Writers - Last Updated: December 12, 2024

Moving beyond the limitation of current retrospective cohorts, the large prospective Myelodysplastic Syndromes Natural History Study (MDS NHS) illustrated annual disease progression rates for MDS of 8% in patients with MDS and 2% among patients at risk for MDS. The presence of genetic mutations and specific cytopenias emerged as key predictors of progression. These findings support the clinical value of targeted interventions for patients at high risk of progression.

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Amy E. DeZern, MD, MHS, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues presented new insights into MDS disease progression and risk stratification based on data from the MDS NHS, a landmark project sponsored by the National Institutes of Health.1 This ongoing research aims to bridge critical gaps in understanding MDS evolution and clinical management strategies. “We are trying to unravel the evolution from one MDS state to another. Currently, our understanding of this evolution, including epidemiologic risk factors and clinal changes, is limited to data from retrospective studies,” said Dr. DeZern. Using the unique, prospective MDS NHS cohort from multiple US centers with extensive clinical data and biospecimens from baseline through follow-up in real time, the researchers assessed rates and potential predictors of MDS progression.2

The study followed up 582 patients with MDS and 505 with at-risk MDS, including clonal cytopenias of undetermined significance. The annual disease progression rate was 8% in patients with MDS and 2% in patients with at-risk MDS. These estimates are lower than reported in previous retrospective analyses. Notably, patients with higher-risk MDS exhibited the steepest progression rates in the first year after diagnosis, highlighting a critical intervention window.

Low hemoglobin, platelet, and neutrophil counts were key predictors of disease progression in patients with MDS. In the at-risk MDS group, low hemoglobin levels were associated with progression. Specific cytopenias and genetic mutations were also associated with disease progression, but additional studies are needed to validate these results in larger cohorts. Yet these specific mutations associated with MDS progression could serve as potential biomarkers for the early identification of high-risk patients.

The findings from the prospective MDS NHS cohort enhance our understanding of the natural history of MDS and provide potential markers of progression that can be leveraged for evidence-based care. Identifying patients at high risk for progression allows for personalized monitoring strategies and timely therapeutic interventions. As the MDS NHS continues to follow up patients for life, its evolving dataset promises to refine treatment paradigms and improve outcomes for individuals across the MDS spectrum.

REFERENCES

 

1 Sekeres MA, Gore SD, Stablein DM, et al. The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes. Leuk Lymphoma. 2019;60(13):3161-3171. doi: 10.1080/10428194.2019.1616186

2 DeZern AE, Otterstatter M, Gillis N, et al. Progression of myelodysplastic syndromes in the MDS Natural History Study (MDS NHS). Abstract #1831. Presented at the ASH Annual Meeting; December 7-10, 2024; San Diego, California.

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