Understanding the Myelodysplastic Syndromes.

The myelodysplastic syndrome (MDS) remains challenging to the clinician in terms of diagnosis and management. The diagnosis is essentially one of exclusion in first ruling out other disorders that can also cause peripheral blood/bone marrow cell dysplasia and cytopenias. The distinguishing biological characteristic of MDS is that it is a clonal disorder of the marrow with impaired differentiation. Recent studies implicate extensive apoptosis as the explanation of the paradoxical observation of marrow hyperplasia but peripheral blood cytopenia. Neutropenia and/or neutrophil dysfunction account for the primary clinical manifestation of MDS in terms of an increased risk for infection, which is the leading cause of death in MDS. The clonal nature of MDS places it also at continual risk for transformation to acute leukemia. Predicting overall survival as well as the risk of AML transformation has been improved by the recent development of a scoring system (International Prognostic Scoring System) that incorporates three laboratory variables: percent of marrow blasts, degree of cytopenias, and presence of chromosomal abnormalities. Based on these variables, four prognostic subgroups can be delineated ranging from low risk with a median survival of 5.7 years, to high risk with a median survival of 0.4 years. Management of MDS can now be based on the patient's respective prognostic subgrouping, with low-risk patients being considered for hematopoietic growth factor singly or in combination if at the point of red cell transfusion dependence and/or neutropenia with recurrent infections, while high-risk patients should be offered AML-induction therapy or novel agents such as topotecan. One must individualize further in patients in the remaining intermediate groups, I and II, in choosing the most appropriate therapy. Future advances upon understanding the molecular details of the MDS clone should ultimately improve the care of patients with MDS.