Minimal Residual Disease in Hematological Malignancies

Accessible online at: www.karger.com/aha Do you prefer quality to quantity? This question has been asked for many years. It is well known that mathematics is the science of pure quantity but what about medicine? For many years, counting cells and identifying them by microscopic inspection have determined the number of normal or abnormal cells in hematological and nonhematological malignancies. During the last decade, several studies have shown that detection and quantification of residual tumor cells significantly correlate with clinical outcome in several types of hematological malignancies. In particular the quantitative measurement of the decrease of the leukemic cell load during the first phases of treatment has a high prognostic value [1]. Detection of minimal residual disease (MRD) is now becoming routinely implemented in treatment protocols and is increasingly used for guiding therapy and for evaluation of new treatment modalities [2]. Methods to detect MRD include technologies designed to detect residual malignant cells beyond the sensitivity of conventional approaches like for example morphology and banding cytogenetics in leukemia. A wide variety of techniques have been developed. The choice of the best method for the particular clinical situation certainly depends on the biology of the individual malignancy, i.e. on the determination of specific markers, which are useful to differentiate between leukemic cells and normal hematopoiesis in leukemic patients. These markers include leukocyte differentiation antigens, fusion transcripts, transcripts overexpressed by mutated or nonmutated genes, rearranged genes, and individual markers, like polymorphic repetitive DNA sequences. In this issue we sought to provide a comprehensive overview on the major technologies for the detection of MRD and their clinical applications. Campana and Coustan-Smith critically discuss advantages and disadvantages of flow cytometry methods in acute leukemias. A special direction of MRD detection is the differentiation between donor and recipient hematopoiesis after allogeneic stem cell transplantation as discussed by Thiede et al. The authors also reviewed the technical issues, advantages and limitations of the methods currently used for chimerism analysis. Adding the morphological analysis of small populations of cells to malignant or recipient-associated markers may improve the accuracy of chimerism and MRD testing, and delineate their clinical significance. Trakhtenbrot et al. introduce the simultaneous analysis of morphology, immunophenotyping and FISH on the same cell, i.e. a multiparametric scanning system. For the comparability of results, an agreement should be reached between various laboratories and different multicenter studies on sample source and volumes obtained (or minimum cell counts) for RT-PCR analyses and regarding the general methods of cell purification, RNA extraction and cDNA synthesis. Rigorous, internationally accepted controls need to be implemented. Muller et al. investigated the impact of preanalytical factors and their standardization. Their review introduces some important considerations for the implementation of RT-PCR-based MRD