The hematopathological basis for studying effects of the demethylating agent 5-aza-2′-deoxycytidine (decitabine) in myelodysplasia
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The myelodysplastic syndromes have, since their first recognition decades ago, been considered notoriously difficult with regard to their proper classification, determination of prognosis, and optimal treatment. With the advent of the French–American–British (FAB) classification, now aided but not superseded by the World Health Organization classification, distinct biological entities have been delineated, which in turn are very useful for stratification to different, established and experimental treatment modalities. However, precise subclassification of different types of myelodysplastic syndrome (MDS) is only possible with hematopathological studies based on the analysis of peripheral blood, bone marrow smear, and bone marrow biopsy, backed by appropriate clinical information. Bone marrow cytogenetics are also essential for any risk stratification since they still provide the second most powerful prognostic parameter after bone marrow blast enumeration. This paper will review the most important aspects of hematopathological diagnostics in MDS, risk scoring, and their application to the inclusion and stratification of patients into the European Organization for Research and Treatment of Cancer (EORTC)/German MDS Study Group Phase III multicenter trial of low-dose decitabine in patients more than 60 years old with high-risk MDS. Emphasis is placed on itemizing the broad spectrum of cytologic and histologic stigmata defining the myelodysplastic categories that are to be considered in this study.