RNA-seq Molecular Risk Classification Refines Prognostic Stratification in Childhood B-Cell Acute Lymphoblastic...

Area of Science:

• Pediatric Oncology
• Molecular Diagnostics
• Cancer Genomics

Background:

• Current risk stratification for childhood B-cell acute lymphoblastic leukemia (B-ALL) relies on clinical factors and early minimal residual disease (MRD).
• These methods may not fully capture the molecular heterogeneity influencing treatment response.
• The Chinese Children's Cancer Group (CCCG)-acute lymphoblastic leukemia (ALL)-2020 protocol guides therapy based on these established risk factors.

Purpose of the Study:

• To evaluate if RNA sequencing (RNA-seq) based molecular risk classification enhances outcome prediction in B-ALL.
• To assess the added prognostic value of RNA-seq beyond existing clinical risk and MRD assessments in the CCCG-ALL-2020 cohort.

Main Methods:

• Retrospective analysis of 531 children with newly diagnosed B-ALL treated under the CCCG-ALL-2020 protocol.
• Classification of patients into favorable, intermediate/other, or adverse risk groups based on RNA-seq.
• Evaluation of standard event-free survival (EFS) and real-world EFS, using Cox models and Harrell's C-index for prognostic performance.

Main Results:

• RNA-seq identified distinct molecular risk groups, with 4-year standard EFS of 85.2% and overall survival of 95.3%.
• Intermediate/other (HR=3.23) and adverse (HR=4.22) molecular risk groups were independently associated with inferior EFS compared to the favorable group.
• Integration of Day-19 MRD and molecular risk significantly improved prognostic accuracy (Harrell's C-index from 0.698 to 0.762).

Conclusions:

• RNA-seq molecular risk classification provides significant prognostic information beyond standard clinical risk and early MRD in B-ALL.
• Transcriptomic risk assessment shows promise for refining prognostic models in B-ALL.
• Further prospective validation is recommended, but RNA-seq is not yet a standalone tool for treatment allocation.