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Updated: Sep 7, 2025
Isolation of Precursor B-cell Subsets from Umbilical Cord Blood
Published on: April 16, 2013
Incidence and prognostic value of central nervous system involvement in infants with B-cell precursor acute
Alexander Popov1, Grigory Tsaur2,3,4, Zhan Permikin2,3
1National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
Insights
Central nervous system (CNS) involvement impacts outcomes in infant B-cell precursor acute lymphoblastic leukemia (BCP-ALL), especially with KMT2A rearrangements. Combining CNS and minimal residual disease (MRD) status improves risk stratification for better treatment allocation.
Area of Science:
- Pediatric Oncology
- Hematology
- Leukemia Research
Background:
- Infants with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) face unique challenges.
- Central nervous system (CNS) involvement is a critical factor influencing treatment outcomes.
- Understanding the interplay between CNS disease and minimal residual disease (MRD) is vital for risk stratification.
Purpose of the Study:
- To determine the incidence of CNS involvement in infants with BCP-ALL.
- To assess the prognostic significance of CNS involvement in this population.
- To explore the relationship between CNS status, MRD, and treatment outcomes.
Main Methods:
- Studied 139 infants with BCP-ALL from the MLL-Baby trial.
- Analyzed cerebrospinal fluid (CSF) for CNS involvement via microscopy.
- Evaluated MRD using flow cytometry and PCR for fusion gene transcripts (FGT).
Main Results:
- CNS involvement was detected in 36% of infants, higher in those with KMT2A rearrangements (44%).
- CNS-positive infants had significantly worse outcomes, particularly with KMT2A rearrangements (EFS 0.21 vs. 0.48).
- Conventional chemotherapy alone was insufficient for CNS-positive infants; combined CNS negativity and FGT-MRD negativity identified a high-prognosis group.
Conclusions:
- Initial CNS involvement and MRD data are crucial for accurate risk-group allocation in infant ALL.
- This combined approach can guide treatment strategies in clinical trials.
- Optimized risk stratification promises improved outcomes for infants with BCP-ALL.
Aim:
The aim of the study was to evaluate the incidence and prognostic impact of central nervous system (CNS) involvement in infants with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), as well as its relation with minimal residual disease (MRD) data.
Methods:
A total of 139 consecutive infants with BCP-ALL from the MLL-Baby trial were studied. Cerebrospinal fluid (CSF) samples were investigated by microscopy of cytospin slides. MRD was evaluated according to the protocol schedule by flow cytometry and PCR for fusion gene transcripts (FGT).
Results:
Involvement of the CNS at any level was found in 50 infants (36.0%). The incidence of CNS involvement was higher in patients with KMT2A gene rearrangements (44.0% for KMT2A-r vs. 15.4% for KMT2A-g, p = .003). The outcome of CNS-positive infants was significantly worse than that of CNS-negative infants, although this prognostic impact was limited to the KMT2A-r group (event-free survival 0.21 for CNS-positive vs. 0.48 for CNS-negative infants, p = .044). CNS-positive infants could not be treated successfully by conventional chemotherapy alone, irrespective of the rapidity of MRD response. In contrast, the combination of initial CNS negativity and FGT-MRD negativity identified a group comprising up to one-third of infants with KMT2A-r ALL who can be treated with chemotherapy and achieve very good outcomes (disease-free survival above 95%), and remaining patients should be allocated to receive other types of treatment.
Conclusion:
We can conclude that this combination of initial CNS involvement and MRD data can significantly improve risk-group allocation in future clinical trials enrolling infants with ALL.
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