Work

Minimal residual disease by high-throughput sequencing in standard risk–favorable pediatric B-lymphoblastic leukemia

Year: 2026

Type: article

Abstract: Most children with B-lymphoblastic leukemia (B-ALL) are cured by modern chemotherapy immunotherapy, but their burden of treatment-related toxicity underscores a need to further refine risk-adapted therapy.Prognostic advances from frontline incorporation of blinatumomab 1 have stimulated interest in testing whether carefully selected, favorable-risk groups might safely benefit from chemotherapy deescalation.The responsible design of such studies requires a clear understanding of how all prognostic information should inform eligibility.Minimal/measurable residual disease (MRD) at the end of induction (EOI) remains one of the strongest predictive tools for guiding postinduction treatment intensity for pediatric B-ALL. 2 High-throughput sequencing (HTS) of clonal immunoglobulin gene rearrangements enhances MRD detection sensitivity below the typical 0.01% threshold of flow cytometry MRD (fcMRD) and provides clinically actionable prognostic information, with the guiding principle that patients who achieve and sustain undetectable HTS-MRD fare better than those with MRD persistence.[3][4][5][6] However, because MRD behaves as a continuous variable with unique, subgroup-specific thresholds, 7,8 the clinical relevance of low-level detection in the context of a specific treatment regimen may not be uniform across all patients.In particular, children classified as Standard Risk-Favorable (SR-FAV) by criteria defined in the Children's Oncology Group (COG) trial AALL1731 1 have consistently outstanding outcomes with chemotherapy alone, 9,10 but the AALL1731 stratification schema, now widely adopted in most of North America, did not incorporate HTS-MRD evaluation for SR-FAV assignment.HTS-MRD has clear prognostic value and is frequently evaluated before final risk group assignment.Thus, defining how EOI HTS-MRD should influence SR-FAV eligibility remains an unresolved gap in current practice.In the largest published pediatric HTS-MRD analysis to date, Wood et al. 3 retrospectively evaluated EOI HTS-MRD using bone marrow samples from a subset of patients from COG AALL0331 11 and AALL0232.12 Of the 296 evaluable National Cancer Institute Standard Risk (age, ≥1 to <10 years; white blood cell count, <50 × 10 3 /μL) patients, 3,13 53 met AALL1731-defined SR-FAV criteria by retrospective classification (Figure 1A).Day 8 peripheral blood (PB) fcMRD was unavailable for 19 patients; therefore, this parameter was omitted from classification.Four patients lacked trackable sequence(s) at diagnosis.Thus, we analyzed the incidence and prognostic relevance of EOI HTS-MRD in 49 SR-FAV patients (supplemental Table 1).

Source: Blood Advances

DOI: 10.1182/bloodadvances.2026020975