Disease characteristics and outcomes of Croatian pediatric patients with acute lymphoblastic leukemia: pretreatment immunophenotypic predictors of high bone marrow minimal residual disease on day 15 of treatment

Aim To assess the clinical-biological characteristics and outcomes of Croatian pediatric patients with acute lymphoblastic leukemia (ALL). A secondary aim was to evaluate the predictive value of pretreatment leukemia-associated immunophenotypes (LAIPs) for poor early response to induction therapy defined as >= 10% day 15 bone marrow flow cytometry minimal residual disease (FCM-MRD). Methods This retrospective cohort study reviewed the medical data of 393 consecutive pediatric ALL patients diagnosed and treated from February 2003 to April2017atfour Croatian pediatric hemato-oncology centers. FCM data of 379 non-infant patients enrolled in two consecutive intercontinental trials, ALL IC-BFM 2002 (NCT00764907) and ALL IC-BFM 2009 (EudraCT 2010-019722-13), were analyzed to evaluate the association between LAIPs at diagnosis and day 15 FCM-MRD >= 10% using univariate and multivariate logistic regression. Results The median age at diagnosis was 5.2 years, with a predominance (83%) of B-cell precursor (BCP) ALL, and high hyperdiploidy (25.1%) and ETV6..RUNX1 (18.7%) as the most common genetic abnormalities. The protocols did not significantly differ in 5-year event-free survival (82.1% vs 81.7%), overall survival (88% vs 85%), and cumulative incidence of relapse (12.3% vs 10%). FCM-MRD >= 10% on day 15 was identified in 22.1% of patients and was predicted by white blood cell (WBC) count >= 20 x 109/L (P = 0.011) and strong expression of CD34 (P = 0.032) and CD13 (P = 0.001) at diagnosis. Conclusion The characteristics and survival rates of Croatian pediatric ALL patients aligned with ALL IC-BFM data. WBC >= 20x 109/L, CD34strong, and CD13strong independently predicted poor early response in BCP-ALL, suggesting a potential prognostic value of LAIPs at diagnosis.