Molecular monitoring of childhood acute lymphoblastic leukemia using antigen receptor gene rearrangements and quantitative polymerase chain reaction technology

Abstract

The use of minimal residual disease (MRD) measurement as a surrogate marker of molecular response to treatment can potentially improve the evaluation of treatment response and enable estimates of the residual leukemic cell burden during clinical remission, thereby improving the selection of therapeutic strategies and, possibly, long-term clinical outcome. The most specific and sensitive methods for MRD monitoring currently available are polymerase chain reaction amplification of rearranged immunoglobulin and antigen-receptor genes, and flow cytometric detection of aberrant immunophenotypes. Several retrospective studies have demonstrated the strong association between MRD and risk of relapse in childhood acute lymphoid leukemia (ALL), irrespective of the methodology used. The promising results on the predictivity of MRD evaluation at the end of induction treatment has challenged the need for a new definition of remission. There is now urgent need to incorporate MRD data into clinical studies, properly designed to address treatment questions, in order to explore whether a better tailored treatment would result in further improvement in cure rates for children with ALL. However, several critical issues must be resolved before MRD determinations can be routinely considered in clinical decision making.