Study of Cell-free DNA in Children and Adolescents With Acute Lymphoblastic Leukemia

Etude de l'ADN Libre Circulant Dans Les leucémies Aigues Lymphoblastiques de l'Enfant et de l'Adolescent

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.

Inclusion Criteria:

ALL population

• 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
• Inclusion before initiation of corticosteroid therapy or chemotherapy
• Written informed consent from legal guardians
• Affiliation to a national health insurance system Control population
• Age < 18 years
• Undergoing blood sampling for HLA typing in the context of bone marrow donor evaluation
• Sibling of a patient with leukemia
• Written informed consent from legal guardians
• Affiliation to a national health insurance system

Exclusion Criteria:

• Pregnant or breastfeeding patients
• Patients not affiliated with a health insurance system