Allogeneic stem cell transplantation (ASCT) is the most definitive curative strategy for patients with acute leukemia (AL), especially those with high relapse risk. Traditionally, the decision to proceed to transplant has been based on static clinical and cytogenetic risk stratification. However, measurable residual disease (MRD) has emerged as a dynamic and sensitive biomarker that allows real-time risk assessment and personalized therapeutic planning. In the review published in Blood Science, researchers examine how MRD can guide transplant indications in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), offering a detailed exploration of MRD detection technologies, transplant decision-making, and future strategies.MRD Detection Platforms
Several platforms are available for MRD detection, each with distinct advantages and limitations. Multiparameter flow cytometry (MFC) remains widely adopted for its rapid turnaround and applicability to most patients. However, operator-dependent variability and sample quality pose challenges to reproducibility. Molecular approaches such as real-time quantitative PCR (qPCR) and digital droplet PCR (ddPCR) provide high sensitivity and specificity for known targets like NPM1 and Ig/TCR rearrangements, but are only applicable when such markers are present. Next-generation sequencing (NGS) broadens MRD detection capabilities by identifying low-frequency variants and tracking clonal evolution but is technically demanding. Single-cell DNA sequencing (scDNA-seq) offers the highest resolution, capable of capturing intra-clonal heterogeneity, yet remains largely confined to research due to cost and complexity. Standardization across centers remains a key challenge, but essential for integrating MRD into clinical workflows.
MRD-Guided Transplantation in AML and ALL
（Blood Science. 7(2):e00229, June 2025.）
In AML, MRD status after induction or consolidation is a powerful predictor of relapse. Persistently MRD-positive patients have a significantly higher risk of relapse and benefit more from ASCT. In contrast, MRD-negative patients, particularly those with favorable-risk cytogenetics, may avoid transplant safely. Chinese AML05 data showed that patients with persistent RUNX1::RUNX1T1 transcripts after consolidation gained significant benefit from ASCT. Similarly, MRD persistence in patients with CBFβ-MYH11 after two consolidation cycles predicted poor prognosis. For intermediate-risk AML, MRD stratification improves transplant selection, with studies such as NCRI AML17 and GMALL validating ASCT for MRD-positive patients in this group. The presence of additional mutations (e.g., FLT3-ITD, DNMT3A, IDH1/2) may further refine this decision, even in patients who achieve MRD negativity.
In ALL, MRD is central to treatment algorithms. GRAALL-2003 and GRAALL-2005 trials established MRD positivity after induction as a reliable predictor of relapse, justifying ASCT in such cases. Conversely, patients who achieve early MRD negativity and are standard-risk may forgo transplant with favorable outcomes. Philadelphia chromosome–positive ALL represents a unique case. Despite the success of tyrosine kinase inhibitors (TKIs), residual MRD following TKI therapy still predicts relapse. Data from Kim et al. suggest that ASCT remains valuable in patients who fail to achieve deep molecular remission. Additionally, certain genetic subtypes such as TP53-mutant ALL, early T-cell precursor (ETP) phenotype, or complex karyotypes may require ASCT irrespective of MRD clearance.
Risk Stratification in MRD-Negative Patients and Future Directions
MRD negativity, while generally associated with favorable prognosis, is not an absolute predictor of long-term remission. Some patients harbor residual subclonal mutations or delayed clearance patterns that elevate relapse risk. In both AML and ALL, MRD-negative patients with stable molecular profiles may safely avoid transplant, but others—particularly those with high-risk genetics—might still benefit from ASCT.
These decisions require balancing relapse risk, transplant-related toxicity, and long-term disease control. A dynamic, integrative risk model that combines MRD kinetics with clinical and genomic features will be essential in refining individualized transplant decisions.
Conclusion
The integration of MRD into the management of acute leukemia has transformed post-remission therapy, offering a more nuanced, biology-driven approach to ASCT. While MRD negativity provides valuable prognostic information, it should be interpreted within the broader context of molecular and clinical risk. The review by Professors Zhao, Chen, and Chang in Blood Science highlights the need for global standardization, dynamic monitoring strategies, and MRD-informed treatment algorithms. As MRD technologies and clinical understanding evolve, personalized transplant pathways are poised to enhance survival while minimizing overtreatment in AML and ALL.
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