Long-Term Clinical and Molecular Dynamics in Hypoplastic Myelodysplastic Neoplasia Treated With Immunosuppressive...

Myelodysplastic neoplasia (MDS) comprises heterogeneous clonal hematologic disorders characterized by peripheral cytopenia, bone marrow dysplasia, and a risk of leukemic transformation. A hypoplastic variant (MDS-h) shares features with aplastic anemia and responds to immunosuppressive therapy (IST). We report three low-risk MDS-h cases treated with IST and monitored over 9-17 years using serial cytogenetic and molecular analyses. All patients achieved transfusion independence after IST, and two experienced durable, long-term remissions. One patient developed late clonal evolution culminating in secondary acute myeloid leukemia. Molecular follow-up revealed diverse mutational dynamics, including stable and fluctuating clones and delayed mutational emergence, detectable in peripheral blood. These findings suggest that in MDS-h, disease activity is largely driven by immune dysregulation rather than early molecular changes, and that repeated IST can yield sustained remissions. However, accumulating mutations may eventually predict malignant transformation, underscoring the importance of long-term molecular monitoring.