Management of high-risk myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are a group of clonal disorders characterized by one or more cytopenias secondary to bone marrow dysfunction. The percentage of bone marrow blasts, the number of cytopenic cell lines and cytogenetics define more precisely clinical risk groups. In the high-risk MDS, the time for evolution to acute myeloid leukemia (AML) is between 0.2 and 1.1 years and the median survival has been evaluated between 0.4 and 1.2 years. Progress in the understanding the biology of MDS and the development of accurate prognostic classification systems have allowed a risk-adapted treatment strategy in individual patients. Some high-risk MDS patient categories may benefit from intensive cytotoxic treatment. Allogeneic stem cell transplantation (alloSCT) from donors remains the treatment of choice for younger patients. Autologous stem cell transplantation (ASCT) may provide a suitable alternative for those patients without a sibling donor or for older patients' categories. New regimens using non-myeloablative stem cell transplantation followed by donor lymphocyte infusions (DLI) are underway and have achieved promising results in HLA-identical transplantation, resulting in reduced morbidity and mortality and confirming that this approach is feasible in patients ineligible for conventional allografting due to age and/or organ toxicity. Other therapeutic strategies include new low-dose treatments, antiapoptotic agents such as amifostine and anticytokine therapy, which are currently under investigation and deserve further evaluation. More insights into the biology of the disease, the discovery of new therapeutic approaches and the search for better ways to use existing strategies may lead to more effective treatments.