Minimal residual disease (MRD) monitoring is a key prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Currently, MRD assessment relies mainly on cellular DNA obtained from bone marrow aspirates. Although highly informative, this approach has limitations, including the need for invasive procedures and the fact that it reflects only the bone marrow compartment.
Tumor cells release fragments of genomic DNA into the bloodstream, known as circulating cell-free DNA (cfDNA). In solid tumors, cfDNA analysis has emerged as a valuable non-invasive biomarker for disease monitoring and treatment response. Recent studies have shown that cfDNA is detectable in pediatric ALL.
This study aims to investigate whether plasma cfDNA analysis could represent an alternative or complementary approach to bone marrow-based MRD assessment. cfDNA may better reflect the global tumor burden across the entire body and allow more frequent longitudinal monitoring during treatment.
The primary objective is to assess the correlation between MRD measured in plasma cfDNA and MRD measured in bone marrow cellular DNA at two key timepoints of treatment: the end of induction (Day 29) and the end of consolidation (Day 71-78).
Secondary objectives include evaluating the correlation between peripheral blood cellular DNA and bone marrow MRD, describing clonal evolution using cfDNA throughout treatment and follow-up, exploring the concordance of genomic alterations detected in cfDNA and other biological compartments, assessing the prognostic value of cfDNA MRD for relapse risk and event-free survival, and characterizing cfDNA fragmentome and methylome signatures in patients compared with healthy controls.
The study will include children and adolescents with newly diagnosed ALL treated at two AP-HP pediatric hematology centers, as well as a control cohort of healthy children undergoing HLA typing for sibling stem cell transplant.
Age < 18 years
Newly diagnosed B-cell or T-cell acute lymphoblastic leukemia
Absence of BCR::ABL1 rearrangement
For infants (<12 months), absence of KMT2A rearrangement
Pregnant or breastfeeding patients
Patients not affiliated with a health insurance system
Study population Children and adolescents with newly diagnosed acute lymphoblastic leukemia treated in participating pediatric hematology centers, as well as healthy pediatric siblings undergoing HLA typing.
Cohort
Prospective
Biological sample collection
Other interventionAdditional peripheral blood samples will be collected during treatment and follow-up for cell-free DNA analysis. Residual samples from bone marrow and cerebrospinal fluid collected as part of standard clinical care will also be analyzed.
Correlation between plasma cfDNA MRD and bone marrow MRD
Pearson correlation coefficient between minimal residual disease (MRD) measured in plasma circulating cell-free DNA and MRD measured in bone marrow cellular DNA. Analyses will be performed according to the type of molecular target used for MRD detection (IG/TCR rearrangements, genomic breakpoints, or pathogenic variants). End of induction (Day 29) and end of consolidation (Day 71-78)
Correlation between peripheral blood cellular DNA MRD and bone marrow MRD
Pearson correlation coefficient between MRD measured in peripheral blood cellular DNA and MRD measured in bone marrow cellular DNA.
Correlation between peripheral blood cellular DNA MRD and bone marrow MRD
Pearson correlation coefficient between MRD measured in peripheral blood cellular DNA and MRD measured in bone marrow cellular DNA. At day 71 to 78
Clonal evolution detected in cell-free DNA
Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up
Clonal evolution detected in cell-free DNA
Mutation profiles of cfDNA across multiple timepoints during treatment and follow-up
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