Management of High-Risk Myelodysplastic Syndrome

摘要: High-risk myelodysplastic syndromes (HR-MDS) are usually defined by the International Prognostic Scoring System (IPSS) risk classes intermediate-2 and high. Untreated patients with HR-MDS have poor prognosis a median survival of less than one year. The discovery clinically-significant activity DNA methyltransferase inhibitors (DNMTi) in MDS has been major advancement. In addition to supportive care, clinical trials, DNMTi therapy, typical therapeutic options for include allogeneic hematopoietic stem cell transplantation (alloHSCT) intensive chemotherapy. Since most not candidates alloHSCT due co-morbidities lack appropriate donors, therapy become standard care first-line HR-MDS. While curative, results hematologic improvements including transfusion-independence, delayed leukemic progression, case azacitidine, prolongation. Many unanswered questions remain regarding optimal use therapy. More data is needed about best schedules, doses, possible combinations sequencing other drugs, biomarkers models predict response, duration Although several cycles before responses typically seen, number role maintenance after achieving response need further exploration. advantage azacitidine extends any hematological but it clear if improved whose stable disease. As more emerges on mechanism action their effects methylation, immune system, cells, synergism agents, deployment these agents will likely result better outcomes Patients primary or secondary resistance dismal very limited options. Development novel ways restore prevent emergence remains high-priority research area. Understanding mechanisms may allow rational design drugs that would sensitivity Several undergoing evaluation elucidation complex pathogenetic disease hopefully development targeted therapies.