Risk Stratification and Updates in Management of MDS

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, resulting in cytopenia’s and an increased risk of progression to acute myeloid leukemia. The diagnosis and classification of MDS have evolved significantly, with the 2022 WHO classification delineating subtypes based on molecular, genetic, and morphological criteria. Risk stratification using the Revised International Prognostic Scoring System and the more recent Molecular International Prognostic Scoring System has enabled more accurate prognosis and personalized treatment strategies. Supportive care—including transfusions, infection prophylaxis, iron chelation, and vaccination remains foundational, particularly in lower-risk MDS. Disease-modifying therapies for lower-risk MDS include erythropoiesis-stimulating agents, lenalidomide, luspatercept, and hypomethylating agents. High-risk MDS patients benefit from more aggressive approaches, including allogeneic hematopoietic stem cell transplantation, which remains the only curative option. Bridging therapy, conditioning regimens, and post-transplant monitoring play vital roles in optimizing transplant outcomes. In less fit or frail patients, hypomethylating agents such as azacitidine and decitabine provide disease control with acceptable tolerability. Emerging targeted therapies—directed at molecular abnormalities offer promising avenues for personalized treatment, especially in relapsed or refractory settings. This review comprehensively discusses the evolving classification, prognostication, and management of MDS, integrating conventional and novel therapeutic modalities, and highlighting current evidence and clinical practice recommendations, with a special focus on the Indian healthcare context.