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Status of minimal residual disease testing in childhood haematological malignancies

In children with acute leukaemia, measurements of minimal residual disease (MRD) provide unique information on treatment response and have become a crucial component of contemporary treatment protocols. In acute lymphoblastic leukaemia (ALL), the most useful MRD assays are based on polymerase chain reaction (PCR) amplification of antigen‐receptor genes, and on flow cytometric detection of abnormal immunophenotypes. The latter is the only MRD assay available for most patients with acute myeloid leukaemia (AML). PCR amplification of chromosomal breakpoints and fusion transcripts can also be used to track MRD in a minority of patients with ALL or AML. Because of the strong correlation between MRD levels and risk of relapse, several ongoing regimens include treatment intensification for children with higher MRD. Treatment de‐intensification for patients with early MRD clearance is also being tested. In addition to their direct clinical application, MRD measurements can be used to better understand the molecular and cellular mechanisms of drug resistance in vivo. The identification of new markers of leukaemia and the use of increasingly sophisticated technologies for detection of rare cells should further facilitate routine monitoring of MRD and elucidate the features of drug‐resistant leukaemic cells.