Patient-specific assays based on whole-genome sequencing data to measure residual disease in children with acute lymphoblastic leukemia – a proof-of- concept study

Risk-adapted treatment in acute lymphoblastic leukemia (ALL) relies on genetic information and measurable residual disease (MRD) monitoring. In this proof-of-concept study, DNA from diagnostic bone marrow from six children with ALL, without stratifying genetics or CNS involvement, underwent whole-genome sequencing to identify structural variants (SVs) in the leukemic blasts. Unique sequences generated by SVs were targeted with patient-specific droplet digital PCR assays, and genomic and cell-free DNA (cfDNA) from bone marrow, plasma and cerebrospinal fluid were analyzed longitudinally. The results indicate that this approach is a feasible option for accurate MRD quantification and that cfDNA may contribute valuable information regarding MRD and low-grade CNS involvement.