TECHNIQUES FOR DETECTION OF MINIMAL RESIDUAL DISEASE

Analysis of leukemia-specific and leukemia-associated markers followin g standard or high-dose treatments is crucial in order to evaluate the efficacy of therapeutic strategies. During the last decade, several t echniques have been proposed and used for detecting minimal residual d isease (MRD). Each approach is characterized by advantages and limitat ions, mainly related to its sensitivity and specificity. The general l imitations of such tests originates from the size of the sample which can be analysed and the heterogeneous distribution of leukemia after t reatment. Clinically useful methods for detecting residual leukemia re quire not only sensitivity but also speed and reproducibility. The rat e of false negative tests is low with polymerase chain reaction as wel l as flow cytometric analysis. Usually, patients without persistent ce lls carrying leukemia-associated markers have a lower risk of relapse. However, the detection of a persistent marker at one time point in co mplete remission cannot be considered a reliable indicator of MRD, whe reas increase of positive signals or reappearance of leukemic markers usually precedes relapse. It is likely that one single approach will n ot allow the monitoring of the majority of patients and that a combina tion of techniques will be needed. Definitive results will be obtained only through prospective studies in patients receiving standardised t herapy. Studies in which therapeutic strategies are designed according to the results provided by techniques for detecting MRD will be neces sary to assess the relevance of their contribution to the treatment of leukemia.