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Clinical Trial
. 2025 May 7;66(2):100-114.
doi: 10.3325/cmj.2025.66.100.

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

Klara Dubravčić  1 , Ružica Lasan Trčić, Ernest Bilić, Josip Konja, Ljubica Rajić, Ranka Femenić, Maja Pavlović, Koraljka Gjadrov Kuveždić, Sunčica Ries, Mirna Sučić, Ivana Franić Šimić, Renata Zadro, Margareta Radić Antolic, Ivana Horvat, Gordana Jakovljević, Jelena Roganović, Srđana Čulić, Dubravka Kuljiš, Višnja Armanda, Karolina Malić Tudor, Senada Šerifi, Bernarda Lozić, Drago Batinić
Affiliations
Clinical Trial

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

Klara Dubravčić et al. Croat Med J. .

Abstract

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 April 2017 at four 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 ≥20×109/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≥20×109/L, CD34strong, and CD13strong independently predicted poor early response in BCP-ALL, suggesting a potential prognostic value of LAIPs at diagnosis.

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Figures

Figure 1
Figure 1
The frequency of major cytogenetic subgroups in Croatian children with acute lymphoblastic leukemia (ALL), shown for (A) the cohort with available cytogenetic results (N = 374) and (B) patients with mixed-lineage leukemia (MLL) rearrangements (N = 14).
Figure 2
Figure 2
Kaplan-Meier survival curves for (A) event-free survival (EFS) and (B) overall survival (OS) in non-infant patients (aged 1–18 years) treated according to the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols. ALL – acute lymphoblastic leukemia; IC-BFM – international consortium Berlin–Frankfurt–Münster.
Figure 3
Figure 3
Cumulative incidence of relapse (CIR) in non-infant patients (aged 1–18 years) treated according to the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols. ALL – acute lymphoblastic leukemia; IC-BFM – international consortium Berlin–Frankfurt–Münster.
See this image and copyright information in PMC

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