A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute...

Area of Science:

• Pediatric Oncology
• Hematology
• Cancer Genomics

Background:

• Intensive treatment is used for high-risk pediatric acute lymphoblastic leukemia (ALL) to prevent relapse.
• However, relapses often occur in standard or medium-risk ALL patients with low minimal residual disease (MRD).
• Accurate risk stratification is crucial for optimizing treatment and improving outcomes in pediatric ALL.

Purpose of the Study:

• To identify recurrent microdeletions and clinical prognostic factors for relapse prediction in non-high-risk precursor B-cell ALL.
• To develop a refined risk stratification model beyond current MRD and NCI classifications.
• To improve therapeutic decisions and cure rates for childhood ALL.

Main Methods:

• Analysis of microdeletions and clinical factors in 475 uniformly treated non-high-risk precursor B-cell ALL patients.
• Development of a predictive risk score (RS) incorporating IKZF1 deletions, P2RY8-CRLF2 fusion, Day 33 MRD, and NCI risk.
• Evaluation of the RS model's performance against MRD-based risk stratification.

Main Results:

• Lower relapse-free survival (RFS) was significantly associated with IKZF1 deletions, P2RY8-CRLF2 fusion, elevated Day 33 MRD, and High NCI risk.
• The developed risk score (RS0, RS1, RS2+) demonstrated distinct RFS (93%, 78%, 49%) and overall survival (OS) (99%, 91%, 71%) rates.
• The RS model provided superior discrimination compared to standard MRD-based risk stratification.

Conclusions:

• The novel risk score effectively stratifies relapse risk in non-high-risk pediatric ALL.
• This RS model offers improved early therapeutic stratification, potentially enhancing cure rates.
• Integrating genetic and MRD data into a comprehensive risk score is vital for personalized ALL treatment.