Myelodysplastic Syndromes in 2026 Brings New Options for Anemia and Risk Scoring

Myelodysplastic syndromes (MDS), now called myelodysplastic neoplasms under the 2022 WHO classification, are heterogeneous myeloid cancers that mostly affect older men and people with prior chemotherapy or radiation. Most patients die from complications of cytopenias rather than leukemic transformation, so careful risk assessment and tailored treatment matter. This narrative review by Garcia-Manero updates diagnosis, risk stratification, and risk-adapted management.

Diagnosis depends on dysplasia seen in bone marrow aspirate and biopsy, with manual blast counts central to risk assessment. Karyotyping remains standard; flow cytometry and FISH are used selectively, and newer tools such as optical genome mapping may lower assay failure. Morphologic diagnostic discrepancy occurs in roughly 20% of initial presentations. Mutation testing helps distinguish MDS from idiopathic cytopenia (ICUS), clonal cytopenia of undetermined significance (CCUS), and age-related clonal hematopoiesis (CHIP). The 5-year progression risk in ICUS rises from about 9% to as high as 82% when a clonal mutation is present. For risk scoring, IPSS-R remains the standard, while the molecular IPSS-M, which incorporates 16 genes and TP53 allelic status, has been validated; the two disagree in about 10% of patients. Comorbidity, which these scores omit, independently affects survival.

For lower-risk disease, therapy is guided by transfusion need and genetics. Erythropoiesis-stimulating agents yield responses in 30% to 60% of patients, and a placebo-controlled trial of darbepoetin showed higher erythroid response. In the COMMANDS trial (363 patients), luspatercept outperformed epoetin alfa, with response in 60.4% versus 34.8% and longer response duration (150 vs 95 weeks). A preplanned analysis suggested a survival advantage (HR 0.805). The author now favors luspatercept first-line for transfusion-dependent patients, including ring sideroblast-negative disease. In the earlier MEDALIST trial in ESA-refractory ring sideroblast disease, 37.9% achieved transfusion independence versus 13.2% on placebo. Imetelstat, a telomerase inhibitor, was tested in the 178-patient IMerge trial and is emerging as an alternative after ESA failure. The supplied text ends during the imetelstat discussion.

For CHIP and CCUS, no data support treatment; patients should be followed in dedicated clinics, risk-scored with CHRS or CCRS, and have comorbidities such as cardiovascular disease managed. Therapy-related cases are of special concern, as prior treatment appears to expand pre-existing mutant clones, including TP53. Allogeneic stem cell transplant remains the only curative approach, and no approved options exist for progression after hypomethylating-agent therapy.

Caveats: this is an expert opinion review, and recommendations reflect one center's practice. The available text is truncated, so the higher-risk and post-HMA sections are not covered here.