The significance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia

In acute lymphoblastic leukaemia (ALL), minimal residual disease (MRD) can be defined as disease occurring at a subclinical level and beyond detection by conventional methods of assessment. Application of the polymerase chain reaction (PCR) to the hypervariable segment of the immunoglobulin heavy chain (IgH) gene, allows detection of MRD at a level of one leukaemic cell in 10(4)-10(5) normal marrow cells. We have performed a retrospective study using this technique in the assessment of children with precursor B-cell ALL in whom the clinical outcome is known. In the early treatment period MRD is commonly detected in children who remain in complete remission on subsequent follow up. Thus, the detection of MRD at this time may have little value in the prediction of future relapse. However, at the end of treatment, children who remain in complete remission have no evidence of MRD. Conversely, detectable MRD at this time would seem to predict for future relapse, though this can be a delayed event. Remarkably, in two children who suffered a bone marrow relapse 8.5 and 9 years after completing therapy for their initial disease, MRD was detected, in their end of initial treatment marrow samples. Clearly PCR technology is changing the definition of the remission state in childhood ALL, and may have predictive value in the assessment of children who are at a high risk of future relapse. Large prospective studies of molecular monitoring are now required to confirm these preliminary results.