Myelodysplastic syndromes: an historical perspective.

In 1900, Leube described a patient with severe megaloblastic anemia, preceding the development of overt leukemia. This case was followed by similar reports of patients characterized by cytopenia, dysmaturation of marrow precursors, an increase of marrow blasts and a significant risk of evolving to acute myeloid leukemia. The first classification of the myelodysplastic syndromes published in 1982 by the French-American-British (FAB) group, sorted out the differences between subgroups with and without an increase of marrow blasts, defined sideroblastic anemia by its characteristic accumulation of mitochondrial iron in erythroblasts, and included chronic myelomonocytic leukemia. During the 1990s, it became clear that additional clinical variables, and in particular chromosome analysis, largely contributed to clinical outcome and that survival and risk for leukemic transformation was significantly worse in patients with adverse cytogenetics. In 1997, patient cohorts from the United States, Europe and Japan were put together and reviewed thoroughly in order to form the database of the International Prognostic Scoring System (IPSS). Based on the number of significant cytopenias, percentage of marrow blasts, and cytogenetic risk profile the IPSS divided patients into four risk categories with significantly different probabilities for survival and risk for leukemic transformation. The IPSS has been extremely useful, and not until recently have new validated risk factors been introduced, the most important being presence of a transfusion need.