Mechanisms and prognostic value of cell kinetics in the myelodysplastic syndromes

Cell kinetics were studied by quantitative autoradiography in 29 patients with myelodysplastic syndromes (MDS) and in four with smouldering leukaemia (SML) in a prospective 6-year study. Cellular turnover in all FAB groups was characterized by reduced labelling index and prolonged DNA synthesis time indicating reduced proliferative activity. Two more parameters were derived from the measurements. (1) The relative cell production rate, which is increased in proerythroblasts and myeloblasts in most cases. This could be attributed to an increased number of divisions in early recognizable precursors in the absence of maturation, and (or) an increased influx from the progenitor compartments. (2) The maturation index of a cell lineage was determined by the ratio of relative cell production rate increase from the first to the last proliferative compartment over the corresponding normal value. It showed a high degree of abnormality in all FAB subgroups, indicating premature cell death in the bone marrow. None of the kinetic parameters proved to be of value in predicting the evolution of leukaemia. In contrast, an excellent correlation was found between the myeloid maturation index and survival (P less than 0.0001). No correlation, however, was found between survival and the erythroid maturation index, which was relatively normal in the worst prognostic group. These findings indicate that although in vitro cell kinetic studies can not predict the evolution of overt leukaemia, the myeloid maturation index is a useful predictor of survival in patients with MDS and SML.