Minimal Residual Disease Studies

Polymerase chain reaction (PCR) and flow cytometry have been used to monitor the persistence of the leukemic clone during treatment in an attempt to identify patients in morphologic and cytogenetic remission, but in whom there is persistence of subclin-ical or minimal residual disease (MRD), which may increase the risk of relapse. These sensitive techniques rely on the ability to identify a unique marker of the leukemia cells. For example, PCR techniques monitor a recurring fusion gene (e.g., BCR-ABL) or a clone-specific rearrangement of the immunoglobulin heavy chain or T-cell receptor gene.19 MRD monitoring by flow cytometry of an aberrant immunophenotype of the leukemic blasts (e.g., presence of myeloid antigens on a lymphoid progenitor cell) can be identified at diagnosis and used for MRD monitoring. These molecular techniques have far greater sensitivity than standard cytogenetic analysis and may detect anywhere from one leukemia cell in a background of 10,000 to 1 million normal cells. Using both semiquantitative and more precise quantitative techniques, a number of studies in both pediatric and adult ALL have now provided preliminary evidence that MRD detection at specific time points following achievement of remission is an independent prognostic factor that may predict early relapse.22-26

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