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Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia
Myriam Campbell1, Csongor Kiss2, Martin Zimmermann3
1Department of Pediatric Hematology and Oncology, Hospital Roberto del Rio, Universidad de Chile, Chilean National Pediatric Oncology Group, PINDA, Santiago, Chile.
Insights
Minimal residual disease (MRD) assessment using flow cytometry (FCM) refined risk groups in pediatric acute lymphoblastic leukemia (ALL). A lower methotrexate (MTX) dose proved effective in preventing relapse for specific patient groups.
Area of Science:
- Pediatric Hematology Oncology
- Clinical Trial Research
- Leukemia Treatment
Background:
- The Berlin-Frankfurt-Münster (BFM) study group investigated pediatric acute lymphoblastic leukemia (ALL).
- Minimal residual disease (MRD) assessment is crucial for refining risk stratification and treatment strategies in ALL.
- Previous risk group definitions relied on factors like age, WBC count, and morphological response.
Purpose of the Study:
- To evaluate the impact of early intensification and methotrexate (MTX) dose on survival in pediatric ALL.
- To assess the utility of flow cytometry (FCM) for minimal residual disease (MRD) detection in ALL.
- To refine risk group stratification using MRD data in the context of the ALL intercontinental-BFM 2002 study.
Main Methods:
- Inclusion of 6,187 pediatric patients (<19 years) diagnosed with ALL.
- Random assignment of intermediate-risk (IR) and high-risk (HR) patients to standard or augmented protocol I phase B (IB) regimens.
- Evaluation of two different methotrexate (MTX) doses (2 g/m² vs. 5 g/m²) every two weeks in precursor B-cell ALL (pcB-ALL) IR patients.
Main Results:
- Overall 5-year event-free survival (EFS) was 75.2% and overall survival (OS) was 82.6%.
- MRD by FCM was successfully assessed in 82.6% of cases, refining risk group outcomes.
- No significant difference in EFS was observed between standard IB and augmented IB regimens (P = .55), nor between MTX doses of 2 g/m² and 5 g/m² (P = .84).
Conclusions:
- Flow cytometry (FCM) is effective for MRD assessment in pediatric ALL.
- A methotrexate (MTX) dose of 2 g/m² was effective in preventing relapse in non-high-risk precursor B-cell ALL (pcB-ALL).
- Augmented protocol I phase B (IB) did not demonstrate advantages over the standard IB regimen.
Purpose:
The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated.
Patients And Methods:
We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR.
Results:
The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84).
Conclusion:
The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].
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