Optimizing Molecular Minimal Residual Disease Analysis in Adult Acute Lymphoblastic Leukemia

Simple Summary Minimal/measurable residual disease (MRD) monitoring is a powerful and independent predictor of outcomes in both children and adult acute lymphoblastic leukemia (ALL). MRD monitoring enables patients' stratification into different risk-adapted treatment arms; it guides treatment decisions in clinical practice, including stem cell transplantation, and represents an early marker of impending relapse. Real-time quantitative PCR is the most widely used molecular method for MRD assessment, but there are some limitations that new approaches may overcome. In this review, we discuss the most recent technological advances in MRD monitoring that are allowing to increase the number of evaluable patients and the levels of quantification and also have the potential to study different disease compartments. Minimal/measurable residual disease (MRD) evaluation has resulted in a fundamental instrument to guide patient management in acute lymphoblastic leukemia (ALL). From a methodological standpoint, MRD is defined as any approach aimed at detecting and possibly quantifying residual neoplastic cells beyond the sensitivity level of cytomorphology. The molecular methods to study MRD in ALL are polymerase chain reaction (PCR) amplification-based approaches and are the most standardized techniques. However, there are some limitations, and emerging technologies, such as digital droplet PCR (ddPCR) and next-generation sequencing (NGS), seem to have advantages that could improve MRD analysis in ALL patients. Furthermore, other blood components, namely cell-free DNA (cfDNA), appear promising and are also being investigated for their potential role in monitoring tumor burden and response to treatment in hematologic malignancies. Based on the review of the literature and on our own data, we hereby discuss how emerging molecular technologies are helping to refine the molecular monitoring of MRD in ALL and may help to overcome some of the limitations of standard approaches, providing a benefit for the care of patients.