Myelodysplastic syndromes: evolution of overt leukaemia by one or several steps of transformation

Summary The evolution of leukaemia was studied prospectively in 29 patients with myelodysplastic syndrome (MDS) followed for 2–6 years by sequential blast counts, cell kinetics derived from quantitative 14 C‐autoradiography and karyotype analysis. Overt leukaemia developed in seven patients. Two distinct patterns of leukaemic evolution were identified. The first was characterized by a gradual increase in blast cell count and in the frequency of labelled blasts, and a corresponding reduction in myeloid maturation index indicating increased intracompartmental myeloblast divisions and premature myeloid cell death. A second pattern of leukaemic evolution was marked by a sudden rise in the blast cell population in a previously stable MDS. This rise was attributed both to an increased rate of blast proliferation, and the accumulation of non‐proliferating blasts. In an additional patient with smouldering ANLL and multiple karyotype abnormalities, transient clinical remission took place following prednisone and oxymetholone therapy, characterized by a sideroblastic morphology, normal karyotype, and persistence of a highly abnormal myeloid maturation index. The sudden emergence of overt leukaemia in previously stable MDS in some of our patients and the temporary reversal of overt leukaemia into sideroblastic anaemia in one case, lend support to the notion of leukaemic evolution by several steps of transformation. On the other hand, the gradual transition of MDS into overt leukaemia in other patients is compatible with a single step leukaemic transformation, although the possibility of clonal disease prior to the development of MDS cannot be excluded with certainty.