Measurable Residual Disease 2.0 in Haematologic Malignancies: Emerging Technologies, Clinical Applications, and Future Perspectives

Measurable residual disease (MRD) assessment has transformed response evaluation and prognostic stratification across hematologic malignancies. Advances in flow cytometry, polymerase chain reaction, next-generation sequencing, and circulating tumour DNA analysis have expanded the sensitivity and biological scope of residual disease detection. However, increasing analytical sensitivity does not necessarily translate into improved clinical utility. This narrative review critically examines contemporary MRD technologies, their analytical limitations, and their applications in acute myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, chronic lymphocytic leukaemia, lymphomas, and chronic myeloid leukaemia. Particular em-phasis is placed on MRD-guided treatment intensification, de-escalation, transplanta-tion decisions, treatment discontinuation, and pre-emptive intervention. Although MRD negativity is strongly associated with favourable outcomes, evidence demon-strating that MRD-guided treatment modification improves survival remains heterogeneous across diseases and therapeutic settings. The review also addresses preanalytical variables, assay validation, laboratory harmonization, standardized reporting, and the complementary role of molecular and immunophenotypic methodologies. Emerg-ing approaches involving artificial intelligence, single-cell profiling, spatial analysis, and multimodal predictive models are discussed. The proposed MRD 2.0 framework emphasizes the transition from increasingly sensitive detection toward integrated, longitudinal, biologically informed, and clinically actionable monitoring. Its successful implementation requires validated laboratory measurements and prospective evidence linking MRD-informed decisions to improved patient outcomes.