Journal: Nature reviews. Clinical oncology
This review article synthesizes current knowledge on myelodysplastic neoplasms (MDS), emphasizing their biological complexity, clinical heterogeneity, and the slow pace of therapeutic progress despite substantial advances in understanding disease biology.
Key points:
- Disease biology and epidemiology
- MDS are clonal myeloid malignancies defined by ineffective hematopoiesis, cytopenias, and variable risk of progression to acute myeloid leukemia.
- They predominantly affect older adults; median age at diagnosis in the US is 76 years.
- The pathophysiology reflects a complex interplay of somatic and germline mutations, immune dysregulation, and a chronically inflamed bone marrow microenvironment.
- Diagnosis, classification, and risk stratification
- Diagnostic tools have improved with broader use of molecular profiling and refined morphologic and cytogenetic criteria.
- Newer classification systems and prognostic models integrate genomic data to better capture disease heterogeneity and to predict outcomes.
- However, evolving definitions and reclassification create challenges for clinical trial design, comparability of historical data, and epidemiologic reporting.
- Therapeutic landscape
- Disease-modifying options remain limited; allogeneic hematopoietic stem cell transplantation is still the only potentially curative therapy.
- Approved therapies for most patients focus on improving cytopenias, delaying progression, and maintaining quality of life rather than cure.
- The article reviews the expanding treatment armamentarium, including established agents and emerging targeted or immune-based strategies, but underscores that relatively few novel agents have translated into approved, practice-changing options.
- Challenges and future directions
- Major barriers include biologic heterogeneity, overlapping molecular drivers across risk groups, and difficulty in designing trials with clearly defined and stable patient subsets.
- The authors highlight the need for:
- Better integration of molecular and microenvironmental insights into risk models and trial eligibility.
- More rationally designed, biomarker-driven therapies.
- Improved clinical trial frameworks that accommodate evolving classifications.
Overall, the review concludes that while our mechanistic understanding of MDS has advanced dramatically, therapeutic progress has lagged, and future gains will depend on translating genomic and microenvironmental insights into precisely targeted, clinically effective treatments.