PCR amplification of fusion transcripts resulting from chromosomal translocations and of IG and TCR gene rearrangements has emerged as a sensitive and reproducible method to monitor MRD in ALL. The measure of the initial response to therapy in patients who have achieved complete remission by morphologic standards can dissect clinical heterogeneity within a genetically homogeneous childhood ALL subgroup. Moreover, MRD monitoring can be applied to the appropriate patient subgroups for early prediction of impending relapses.
However, before any application in clinical decision making, the MRD value must be studied in the context of prospective controlled trials. Moreover, high levels of confidence in interpreting MRD results are needed to rule out false-positive and false-negative tests, considering the problems and pitfalls of the current technology. In this context, international standardization is needed for the interpretation of MRD results produced by different studies.
MRD analysis should be incorporated into any future clinical studies investigating a therapeutic question. Moreover, only the combination of simplification and reliability of MRD methods will allow the potential benefits of MRD monitoring to be extended to all children with leukemia. In addition, new technologies such as microarrays can be of great value to identify new genetic lesions in patients carrying the same genetic subtypes of ALL but with different MRD clearance and to identify new specific markers for MRD monitoring.
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