Improved survival in pediatric acute lymphoblastic leukemia through therapy intensification based on minimal residual
Hyery Kim1, Su Hyun Yoon2, Sunghan Kang2
1Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. taban@hanmail.net.
Insights
Minimal residual disease (MRD) monitoring and intensified therapy significantly improve survival for pediatric acute lymphoblastic leukemia (ALL). This approach optimizes risk-adapted treatment strategies, leading to better outcomes for both standard-risk and high-risk patients.
Area of Science:
- Pediatric Oncology
- Hematologic Malignancies
- Clinical Trial Analysis
Background:
- Minimal residual disease (MRD) guided therapy is the standard for pediatric acute lymphoblastic leukemia (ALL).
- Risk stratification and treatment intensification are crucial for optimizing patient outcomes.
- Understanding the interplay between MRD levels and risk groups is essential for refining treatment protocols.
Purpose of the Study:
- To assess the impact of MRD-driven treatment intensification in pediatric ALL.
- To evaluate the effectiveness of MRD-guided therapy in conjunction with protocol-defined risk groups.
- To determine if intensified therapy improves survival outcomes in pediatric ALL patients.
Main Methods:
- Retrospective analysis of 209 pediatric ALL patients treated between 2013 and 2023.
- MRD assessment using flow cytometry at critical treatment junctures.
- Treatment intensification based on MRD levels (≥0.1%) and risk stratification (NCI, cytogenetics).
Main Results:
- Overall 5-year survival rates were 92.5% (OS) and 84.3% (EFS).
- Treatment intensification significantly improved event-free survival (EFS) in high MRD patients (94.2% vs. 75.5%, p=0.04).
- MRD-based intensification eliminated survival differences between rapid and slow early responders and improved outcomes in post-induction high MRD patients.
Conclusions:
- MRD-guided therapy intensification markedly improves survival outcomes in pediatric ALL.
- Combining MRD monitoring with risk-based protocols optimizes risk-adapted treatment strategies.
- MRD monitoring is vital for tailoring therapy and improving survival in pediatric ALL.
Purpose:
Minimal residual disease (MRD)-guided therapy is the global standard treatment for pediatric acute lymphoblastic leukemia (ALL). We assessed the impact of MRD-driven intensification along with protocol-defined risk groups in pediatric ALL treatment.
Methods:
This retrospective analysis included 209 patients with ALL (treated between January 2013 to June 2023). MRD was assessed using six- to eight-color flow cytometry at the end of each phase before the maintenance phase. Post-induction treatment was determined based on early response, National Cancer Institute risk, and cytogenetics. High-risk (HR) patients followed the Korean HR or CCG-1882 protocols and standard-risk (SR) patients followed the modified COG-AALL0331 protocol. Treatment was intensified if flow-MRD ≥ 0.1% was identified.
Results:
Overall, 103 and 106 patients were classified as having SR and HR, respectively. The 5-year overall survival (OS) and event-free survival (EFS) were 92.5% and 84.3%, respectively. Thirty SR and 18 HR patients received intensified chemotherapy. Treatment intensification significantly improved EFS in patients with high MRD (94.2% vs. 75.5%, p = 0.04), particularly in post-induction patients with high MRD (90.0% vs. 19.0%, p = 0.035). The difference in survival between rapid early responder (RER) and slow early responder (SER) groups was eliminated after MRD-based intensification. The implementation rates of treatment intensification varied over time (9.1% before 2015, 28.6% during 2016-2019, and 13.9% during 2020-2023), reflecting improved risk stratification and therapy selection.
Conclusion:
MRD-guided therapy intensification markedly improved survival outcomes in patients with pediatric ALL when combined with risk-based protocols, highlighting the importance of MRD monitoring for optimizing risk-adapted treatment strategies.
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