Immunoglobulin NGS enhance residual disease detection and prognosis in pediatric Ph+ acute lymphoblastic leukemia

TL;DR

This study shows that immunoglobulin next-generation sequencing improves detection of residual disease and predicts outcomes in children with a specific type of leukemia.

Contribution

The study demonstrates that Ig-NGS provides more accurate and earlier prognosis and monitoring of clonal evolution in pediatric Ph+ B-ALL compared to conventional methods.

Findings

Ig-NGS detected lower malignant clonal cells at diagnosis correlated with better relapse-free survival.

Ig-NGS MRD negativity at the end of induction was linked to improved two-year survival.

Specific IGH gene usage and clonal evolution patterns were associated with prognosis.

Abstract

In pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ B-ALL), the clinical value of highly sensitive minimal residual disease (MRD) detection by immunoglobulin next-generation sequencing (Ig-NGS), and its role for tracking clonal evolution, remains inadequately characterized. In this study, we evaluated MRD in a cohort of pediatric Ph+ B-ALL patients using Ig-NGS in parallel with conventional methods, including flow cytometry (FCM) and BCR-ABL reverse transcription polymerase chain reaction (RT-PCR). Malignant clonal burden at diagnosis, MRD kinetics, and immunoglobulin heavy chain (IGH) clonal evolution were analyzed for their prognostic relevance. We observed that a lower percentage of malignant clonal cells detected by Ig-NGS at diagnosis was associated with improved relapse-free survival (RFS) (p < 0.01). Ig-NGS-derived pre-treatment malignant clone burden showed stronger association with relapse risk compared with FCM or RT-PCR. Furthermore, Ig-NGS MRD negativity at the end of induction (EOI) was associated with superior two-yeas RFS (p = 0.01), and Ig-NGS detected molecular relapse earlier than FCM or RT-PCR in some patients. Specific IGHV and IGHJ gene usage patterns and the extent of V-replacement clonal evolution at diagnosis were also correlated with prognosis. In summary, these findings suggested that Ig-NGS based MRD assessment may provide enhanced prognostic stratification and enable dynamic monitoring of clonal evolution in pediatric Ph+ B-ALL. Its integration into routine clinical practice may enhance early relapse prediction and support more precise risk-adapted therapeutic decisions.

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