Measurable Residual Disease detection in acute lymphoblastic leukaemia: comparison between targeted NGS and ASO-RQPCR

Measurable residual disease (MRD) testing ​in acute lymphoblastic leukaemia (ALL) is considered standard of care as it is the strongest prognostic factor predicting disease outcome and is critical in therapeutic decision-making and assessing response to therapy. Across many centres, allele-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQPCR) has been the gold standard for assessing MRD in ALL patients for over 20 years. More recently, next-generation sequencing (NGS) technology has rapidly developed, with several platforms currently available for ALL MRD assessment. Comparative analysis between NGS and ASO-RQPCR is vital to ensure quality performance and to guide future use. Using longitudinal samples from 10 patients in a real-world clinical setting, we correlated the results of the Invivoscribe LymphoTrack system for NGS and ASO-RQPCR. Across the 10 patients, 63 timepoints were analysed showing nine discordant samples, six NGS⁺/PCR^- ​and three PCR⁺/NGS^-. Our findings are consistent with previous literature ​that the two methodologies are highly concordant in ALL MRD assessment (r=0.89). We also demonstrate that NGS has a greater quantitative range allowing for earlier detection of relapse in some cases. Furthermore, in our study, NGS was able to identify an MRD marker in more patients than ASO-RQPCR. Therefore, NGS MRD has potential advantages; however, clinical trials are required to evaluate clinical impact.