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KEY CONCEPTS

KEY CONCEPTS

  • image Myelodysplastic syndromes (MDS) primarily affect elderly adults, with median age at diagnosis of 76 years.

  • image MDS are associated with environmental, occupational, and therapeutic exposures to chemicals or radiation.

  • image The clonal population of cells manifested as MDS results from enhanced self-renewal of a hematopoietic stem cell or acquisition of self-renewal in a progenitor cell, increased proliferative capacity in the abnormal clone, impaired cell differentiation, evasion of immune regulation, and antiapoptotic mechanisms in the disease-sustaining cell.

  • image Most patients with MDS present with fatigue and lethargy or symptoms related to anemia-induced tissue hypoxia.

  • image The prognosis of patients with MDS is variable. Overall survival time ranges from a few months to several years and is most accurately estimated with the International Prognostic Scoring System—Revised (IPSS-R).

  • image The primary goal of therapy is hematologic improvement for lower-risk patients and alteration in the natural course of the disease for higher-risk patients. Palliation of symptoms and improvement in quality of life are goals of therapy for all patients.

  • image Current guidelines recommend erythropoietin (EPO) or darbepoetin with or without filgrastim for management of anemia in patients with lower-risk MDS.

  • image Hypomethylating agents are appropriate for patients with lower-risk MDS with clinically significant neutropenia or thrombocytopenia, patients with anemia who are unlikely to respond to or have not responded to a trial of EPO or immunosuppressive therapy.

  • image Antithymocyte globulin is appropriate treatment for patients with lower risk, HLA DR15 positive expressing MDS who have symptomatic anemia that is unlikely to respond to erythropoietic agents.

  • image Lenalidomide is recommended for initial treatment of lower-risk 5q- syndrome accompanied by symptomatic anemia.

  • image Allogeneic hematopoietic stem cell transplantation offers potentially curative therapy to patients with MDS who have a donor and are healthy enough for the procedure.

Myelodysplastic syndromes (MDS) are myeloid clonal, heterogeneous, stem cell disorders characterized by predominantly hypercellular bone marrows, anemia, thrombocytopenia, leukopenia, and an inherent predisposition toward evolution to acute myeloid leukemia (AML).1,2 The diagnostic hallmark for MDS is the presence of bone marrow dysplasia in at least 10% of cells of a single myeloid lineage.1 The clinical course of patients with MDS varies from a slowly progressing indolent disease to more aggressive disease characterized by excess bone marrow blasts and rapid progression to AML in up to 30% of cases.3,4

Our understanding of the molecular genetics behind MDS has advanced in recent years, but few targeted treatments have been approved in MDS. Aberrations in epigenetic regulator genes, spliceosome component pathways, DNA damage response genes, and genes regulating transcription factors have redefined the molecular landscape in MDS and several additional chromosomal abnormalities have been incorporated into prognostic models predicting survival and leukemic transformation.5,6 Between 2004 and 2006, three medications (azacitidine, decitabine, and lenalidomide) were approved by the FDA for the treatment of MDS with both azacitidine and lenalidomide improving survival in MDS.7,8 Despite progress in disease classification, identification of over 40 ...

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