Prognostic factors influencing relapse and survival of childhood acute lymphoblastic leukemia with the ALL-BFM IC 2009 protocol

Abstract Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, remaining the fourth leading cause of death among children aged 1 to 15 in Turkey. Although treatment outcomes have improved significantly with MRD-based risk stratification and intensive chemotherapy regimens like ALL-BFM IC 2009 protocol, relapse and early mortality remain significant barriers to cure. Methods: A retrospective analysis of data from children diagnosed with ALL and treated between January 2016 and January 2025 according to the original ALL-BFM IC 2009 protocol were identified. The study excluded patients younger than 1 year (n = 5), those with biphenotypic (n = 2) or secondary leukemia (n = 3), those referred to an external center after diagnosis (n = 12), those not at remission after induction (n=1), and those who were diagnosed and began treatment at another center but later continued their treatment at our hospital (n = 5). The final analysis included 113 children between the ages of 1 and 18 years who had completed induction chemotherapy prior to the study's commencement. This study was approved by the ethics committee (SBA 25/135) Results: The median age was 4 years, with 54% male patients. Most were classified as intermediate risk (55.4%) or standard risk (26.8%). Pre-B cell phenotype predominated (88.5%). Overall, 20 patients (17.7%) relapsed and 11 (9.7%) died. The 5-year Overall Survival (OS) was 88.3% (95% CI: 81.8–95.2%) and Event Free Survival (EFS) was 84.4% (95% CI: 77.3–92.1%). Relapse risk was significantly higher in children older than or equal to 6 years (p=0.004) and those with White Blood Cell (WBC) > 100,000/mm³ at diagnosis (p=0.029). Logistic regression identified age ≥6 years (OR=3.87, 95% CI: 1.32–11.34, p=0.011) and WBC >100,000/mm³ (OR=4.35, 95% CI: 1.03–18.43, p=0.046) as independent predictors of relapse. The predictive model had 83.2% accuracy and AUC=0.727. Survival analyses showed significantly reduced OS and EFS in patients with WBC >100,000/mm³ (log-rank p=0.003 and p=0.004, respectively). Cox regression confirmed WBC as an independent predictor of mortality (HR=2.76, p=0.008). All 11 deaths occurred in patients who relapsed (p<0.001), with median OS in this group of 48 months. Conclusion: The restricted mean OS of 98.411 months and EFS of 92.07 months; estimated 5-year OS rate of 88.3% and EFS rate of 84.4% observed in our study group is consistent with the success rates reported in other studies that utilized the ALL IC-BFM 2009 protocol. Among the prognostic factors, WBC count at diagnosis emerged as the strongest predictor of poor outcomes.