By Dr Sarah Lawson

Flow Cytometric Analysis of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) is the commonest childhood malignancy affecting approximately 450 children per year in the UK. Modern treatment results in cure in approximately 80% and patients receive different intensities of treatment according to their risk of relapse. One of the factors used to risk stratify patients is the level of minimal residual disease (MRD) present during treatment. MRD is currently measured by molecular methods at day 28 and week 11 of treatment. This methodology is sensitive and specific but is not applicable to all patients and is costly and timely.

Flow cytometric MRD analysis offers a number of advantages over molecular MRD analysis. It is widely available, offers equivalent or higher technical applicability, has quick turnaround times, offers the ability to assess very early treatment response and is cheaper.

Flow cytometric MRD analysis relies on the identification of aberrant antigen expression by leukaemic blasts. Identification of these aberrant immunophenotypes allows detection of leukaemic cells at a sensitivity of 1 in 10⁴ and is specific for leukaemic cells.

The UK Flow MRD Laboratory Network was established in 2002 with representatives from Birmingham, Bristol, Glasgow and Sheffield. The network has since expanded and now includes two further laboratories – Newcastle and Royal London. The network laboratories work from a common SOP, have regular workshops and a website for reporting and reviewing results. Results are all centrally reviewed. This laboratory network is coordinated by Mrs Jenny Jesson and Dr Sarah Lawson at Birmingham Children’s Hospital. The network provides quality assured results of MRD analysis in childhood ALL at day 28 and week 11 of treatment.

Our research to date shows that flow cytometric MRD analysis is feasible, applicable and predictive of relapse in childhood ALL. It is cheaper than current molecular methodology and offers the advantage of quicker turnaround times and the ability to assess very early treatment response.

Further work on its exact role in the management of childhood ALL in the UK is ongoing within the UK Flow MRD Laboratory Network.

Our hope is that flow cytometric analysis of MRD in childhood ALL will be incorporated into routine management. This will allow MRD assessment, the most significant predictor of relapse in childhood ALL, to be available to more patients allowing individualisation of therapy according to each patient’s risk of relapse thus avoiding both under treatment and its associated risk of relapse and overtreatment with its associated morbidity and mortality. The ultimate aim is to cure as many children with ALL as possible with as little toxicity as possible.