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Original scientific paper

https://doi.org/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 ; Division of Flow Cytometry, Department of Laboratory Diagnostics, Children’s Hospital Zagreb, Zagreb, Croatia *
Ružica Lasan Trčić ; Division for Cytogenetics, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croati
Ernest Bilić ; Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
Josip Konja ; Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
Ljubica Rajić ; Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
Ranka Femenić ; Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
Maja Pavlović ; Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
Koraljka Gjadrov Kuveždić ; Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia
Sunčica Ries ; Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia
Mirna Sučić ; Division of Cytology, Department of Pathology and Cytology, Sveti Duh University Hospital, Zagreb, Croatia
Ivana Franić Šimić ; Division for Cytogenetics, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Renata Zadro ; Department of Laboratory Diagnostics, St Catherine Specialty Hospital, Zagreb, Croatia
Margareta Radić Antolic ; Division of Laboratory Hematology and Coagulation, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Ivana Horvat ; Medical- biochemical laboratory, Polyclinic Analiza, Varaždin, Croatia
Gordana Jakovljević ; Department of Oncology and Hematology, Children’s Hospital Zagreb, Zagreb, Croatia
Jelena Roganović ; Department of Oncology and Hematology, Children’s Hospital Zagreb, Zagreb, Croatia
Srđana Čulić ; Department of Pediatrics, University Hospital of Split, Split, Croatia
Dubravka Kuljiš ; Department of Pediatrics, University Hospital of Split, Split, Croatia
Višnja Armanda ; Department of Pediatrics, University Hospital of Split, Split, Croatia
Karolina Malić Tudor ; Department of Pediatrics, University Hospital of Split, Split, Croatia
Senada Šerifi ; Department of Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital Center Rijeka, Rijeka, Croatia
Bernarda Lozić ; Department of Pediatrics, University Hospital of Split, Split, Croatia
Drago Batinić ; Division of Laboratory Immunology, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia

* Corresponding author.


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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 immunopheno
types (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 hy
perdiploidy (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.

Keywords

Hrčak ID:

352477

URI

https://hrcak.srce.hr/352477

Publication date:

23.4.2025.

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