Myelodysplastic syndrome (MDS) is a clonal neoplastic myeloid stem cell neoplasm characterized by ineffective hematopoiesis in the bone marrow and cytopenias in the peripheral blood. Prognostic scoring systems classify patients as low-risk or high-risk MDS. Various prognostic scoring systems have been developed to predict disease course and survival using markers such as cytopenias, bone marrow blast ratio, cytogenetics, age, and performance status. The most commonly used scoring systems are the IPSS and R-IPSS. In its 2022 classification, the WHO used the term myelodysplastic neoplasms instead of myelodysplastic syndromes. These clonal hematopoietic neoplasms were defined by cytopenias and morphological dysplasia, with a dysplasia threshold of 10% for all series. MDS subtypes were grouped into those characterized by genetic abnormalities and those defined by morphology. Although patients may be classified as low risk based on their current MDS risk scores, the disease is a blood cancer with a generally poor prognosis. Patients with high and very high IPSS-R risk can expect a median survival of 1.6 and 0.8 years, respectively, while those with intermediate, low, and very low IPSS-R risk have a median survival of 3, 5.3, and 8.8 years, respectively.

The treatment approach for high-risk MDS is aimed at delaying leukemic transformation and prolonging survival. Currently, the only curative treatment for high-risk MDS patients is allogeneic stem cell transplantation (HSCT). Its application is limited by the advanced age and lack of vigor of many MDS patients. All "high-risk" MDS patients with good performance status and without serious comorbidities should be considered for curative allogeneic HSCT. Transplant-related factors have also been shown to play a role in determining post-transplant prognosis. Treatment options for patients ineligible for transplantation are limited, and HMA remains the standard of care. New agents are under development for high-risk MDS patients. In recent years, several new drugs have been tested in combination with 5-azacitidine to further improve patient outcomes, but these have been unsuccessful. A randomized phase II SWOG trial compared standard azacitidine with azacitidine combined with lenalidomide or vorinostat in 227 patients with HR-MDS, reporting an overall response rate of 38% in the azacitidine group, while no improvement in response or survival was seen in the combination group. The recent approval of venetoclax, a BCL-2 inhibitor, for use with 5-azacitidine in AML has prompted investigation of this combination in MDS. In particular, azacitidine + venetoclax, azacitidine + sabatolimab, and azacitidine + magrolimab have shown encouraging results in large, single-arm studies and have also improved in placebo-controlled, double-blind studies with OS as the primary endpoint. IDH1 or IDH2 mutations occur in 5–15% of MDS patients, and enasidenib and ivosidenib have been shown to produce responses in MDS patients with IDH2 mutations. It may be mentioned that the new ICC, which classifies previous WHO 2016 MDS with ≥10% blasts as MDS/AML, would potentially allow the use of AML-approved drugs also in higher-risk MDS