# Clinical Impact of Immunoglobulin Heavy Chain Clonality in Pediatric B‐Cell Precursor Acute Lymphoblastic Leukemia

## TL;DR

This study shows that analyzing immunoglobulin heavy chain clonality in pediatric B-cell leukemia can improve risk assessment and relapse prediction.

## Contribution

The study introduces a novel method for risk stratification using RNA sequencing of IGH clonality in pediatric BCP-ALL.

## Key findings

- IGH clonality analysis identified three distinct prognostic groups in BCP-ALL patients.
- Patients with high hyperdiploidy showed significant survival differences based on IGH clonotype.
- Relapse often involved newly expanded clones, especially in high hyperdiploidy cases.

## Abstract

Recent advancements in risk stratification have greatly improved outcomes in pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). Despite favorable prognostic indicators, including the absence of cytogenetic abnormalities and minimal residual disease (MRD) negativity, relapse remains a major clinical concern.

We investigated the clinical significance of immunoglobulin heavy chain (IGH) clonality using RNA sequencing data in BCP‐ALL. We analyzed IGH clonality from 136 patients. IGH abundance followed a power law distribution, which enabled us to identify disease clones as outliers based on read count. In total, 330 disease clones were detected, and patients were categorized into three clonotype groups: undetectable disease clone (UDC), incomplete disease clone (IDC), and complete disease clone (CDC). Clinical outcomes were compared across clonotypes, including in subgroups with high hyperdiploidy (HHD) and MRD negativity. Among patients with HHD, significant prognostic differences were observed across clonotypes (event‐free survival [EFS], p = 0.01; overall survival [OS], p = 0.08), even among those who were MRD‐negative (EFS, p = 0.01; OS, p = 0.03). Furthermore, comparisons of IGH sequences between diagnosis and relapse indicated that while initial disease clones often contributed to relapse, newly expanded clones frequently emerged, particularly in patients with HHD.

These findings highlight the importance of analyzing the IGH repertoire in refining risk stratification and underscore the need for advanced sequencing‐based MRD monitoring.

IGH clonality analysis by RNA sequencing revealed distinct prognostic groups in pediatric BCP‐ALL. Our results demonstrate the value of sequencing‐based IGH profiling to enhance relapse risk assessment and guide precision monitoring strategies.