Journal
HAEMATOLOGICA
Volume 107, Issue 12, Pages 2783-2793Publisher
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2022.280638
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Funding
- American Society of Hematology Research Training Award
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Measurable residual disease (MRD) is a strong predictor of relapse risk and survival in acute lymphoblastic leukemia (ALL). Various methods, including next-generation sequencing, can evaluate MRD levels. Immunotherapy approaches have shown efficacy in eradicating MRD in B-ALL, but T-ALL remains a challenge. As MRD detection and novel therapeutics advance, MRD will play an increasingly important role in ALL therapy.
Measurable residual disease (MRD) is the most powerful independent predictor of risk of relapse and long-term survival in adults and children with acute lymphoblastic leukemia (ALL). For almost all patients with ALL there is a reliable method to evaluate MRD, which can be done using multi-color flow cytometry, quantitative polymerase chain reaction to detect specific fusion transcripts or immunoglobulin/T-cell receptor gene rearrangements, and high-throughput next-generation sequencing. While next-generation sequencing-based MRD detection has been increasingly utilized in clinical practice due to its high sensitivity, the clinical significance of very low MRD levels (< 10-4) is not fully characterized. Several new immunotherapy approaches including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T-cell therapies have demonstrated efficacy in eradicating MRD in patients with B-ALL. However, new approaches to target MRD in patients with T-ALL remain an unmet need. As our MRD detection assays become more sensitive and expanding novel therapeutics enter clinical development, the future of ALL therapy will increasingly utilize MRD as a criterion to either intensify or modify therapy to prevent relapse or de-escalate therapy to reduce treatment-related morbidity and mortality.
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