Minimal residual disease monitoring in childhood acute lymphoblastic leukemia

This review summarizes recent advances in the application of minimal residual disease (MRD) testing in childhood acute lymphoblastic leukemia (ALL).

Polymerase chain reaction amplification of antigen receptor genes, one of the two main methods to study MRD in ALL, could be made more rapid, sensitive and informative by the application of next-generation sequencing technologies. Advances in flow cytometric detection of MRD, the other main method, include the identification of new immunophenotypic markers to recognize ALL cells, the development of computerized approaches to automate data analysis, and the generation of instruments that can rapidly screen large number of cells for immunophenotypic abnormalities while visualizing their morphology. Recent data further corroborate the prognostic value of MRD at early time points during therapy, demonstrate the prognostic significance of MRD among ALL subtypes, and indicate that presenting features can complement the prognostic utility of MRD.

MRD is replacing morphology to measure treatment response in ALL and is being used, with promising results, for risk-stratification in clinical protocols. Recent studies provide further evidence of its prognostic significance and point to possible strategies to increase the reliability, applicability and sensitivity of MRD testing.