Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool for guiding therapeutic choices. In recent years, thanks to real-time quantitative PCR (qPCR), MRD monitoring has further achieved higher levels of sensitivity and standardization. However, some outstanding issues still remain to be addressed and emerging technologies hold the promise of improving MRD detection in ALL patients. Areas covered: Through a comprehensive review of the literature, we analyze the state-of-the-art of molecular MRD assessment in ALL to better understand how, in the upcoming years, some of its limitations could be tackled by emerging molecular technologies. Furthermore, we highlight the future role of molecular MRD monitoring in the context of personalized protocols, taking into account the growing genetic complexity in ALL. Expert commentary: Although new molecular technologies are promising tools for MRD assessment, qPCR still remains the gold standard for evaluating MRD in ALL. High-throughput sequencing and droplet digital PCR allow to identify new prognostic factors and/or MRD targets at diagnosis and to perform earlier MRD evaluations, thereby optimizing patient stratification and earlier MRD-based clinical intervention to improve ALL patient outcomes.
Keywords: MRD-guided clinical trials; Minimal residual disease; PCR-based high-throughput sequencing; acute lymphoblastic leukemia; droplet digital PCR; immunoglobulin and T-cell receptor gene rearrangements; real-time quantitative PCR.