Pediatric B-Cell Acute Lymphoblastic Leukemia: Comprehensive Genomic Characterization Including SNP-Array and Analysis of Relapse Risk

Background: Accurate identification of pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients at increased risk of relapse remains a major clinical challenge, as relapse occurs in 10–20% of cases, including patients initially classified as low- or intermediate-risk. This study aimed to identify clinical, genomic, and measurable residual disease (MRD) related predictors of relapse in pediatric B-ALL. Methods: 51 pediatric patients with B-ALL were included and followed for a median of 30.5 months (IQR, 16–45.5). Patients were stratified according to relapse status. At diagnosis, all cases underwent comprehensive genomic characterization based on the 2022 WHO and ICC classifications, including SNP-array analysis to identify copy number alterations (CNA) involving recurrent B-ALL genes (IKZF1, CDKN2A/B, PAX5, ETV6, BTG1, EBF1, ERG, RB1, and PAR1) and to determine IKZF1plus status. Clinical variables, including white blood cell count, cytogenetic risk, and MRD assessed by flow cytometry at day 15, day 33, and at the end of induction, were analyzed. Kaplan–Meier and Firth-penalized Cox regression analyses were performed to identify independent predictors of relapse. Results: 86.3% of patients were classified according to the 2022 WHO/ICC classifications, with high hyperdiploidy being the most frequent subtype. During follow-up, 11 patients relapsed. Relapse was significantly associated with high cytogenetic risk (p = 0.007) and showed a trend toward association with an adverse CNA profile (p = 0.075). Patients with >25% bone marrow blasts at day 15 (p < 0.001) and those with positive MRD at the end of induction (p = 0.017) had a significantly higher risk of relapse. In multivariable analysis, high genetic risk and positive end-of-induction MRD remained independent predictors of relapse, with hazard ratios (HRs) of 9.31 (95% CI, 1.55–56.1), p = 0.010, and 10.9 (95% CI, 2.39–49.9), p = 0.002, respectively. Conclusions: An integrated diagnostic strategy including SNP-array provides a high diagnostic yield. High-risk cytogenetic abnormalities and positive end-of-induction MRD are independent predictors of relapse in pediatric B-ALL. Their combined assessment at diagnosis and early treatment may improve risk stratification and may support personalized therapeutic approaches.