NGS versus High sensitivity Cytometry to detect minimal residual disease in acute lymphoblastic leukemia

The concept of acute lymphoblastic leukemia (ALL) as a mono or oligoclonal disease has been replaced by a disease with a clonal heterogeneity yet at the time of diagnosis. This clonal heterogeneity, partly responsible for treatment resistance and relapse, is not taken into account in the diagnosis and during the follow up by the current methods of minimal residual disease (MRD) assessment. The NGS (next generation sequencing), allows the detection and monitoring of this clonal heterogeneity and thus it could be useful for MRD assessment. This project aims to compare the high sensitivity flow cytometry, currently used in clinics for MRD assessment, with the NGS in 50 children and 75 adults with ALL treated within risk-adapted Spanish protocols. In each sample at diagnosis and during follow-up the MRD will be assessed by flow cytometry and NGS. We are interested in determining which of the two techniques is able to identify and follow more accurately the resistant clone(s) during the treatment, and thus to reduce the percentage of false negative MRD values observed by flow cytometry. If we demonstrate that NGS is more sensitive and specific than flow cytometry, we can use NGS to optimize the therapeutic strategies based on the MRD assessment in children and adult patients with ALL.