Articles, Issue 2/2026, Брой 2/2026, Брой 2/2026, Articles

Diagnosis and risk stratification of acutelymphoblastic leukemia:

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DOI: 10.66223/pediatria.2026.2.001

H. Burnusuzov

Department of Pediatrics, Medical University – Plovdiv Competence Center “Perimed-2” – Plovdiv Department of Pediatrics, University Hospital “Pulmed” – Plovdiv

Abstract

The diagnosis and risk stratification of acute lymphoblastic leukemia (ALL) has undergone a fundamental evolution with the introduction of the 5th edition of the WHO classification (WHO 2022) and the International Consensus Classifier (ICC 2022). These systems require the integration of morphological, immunophenotypic and precise molecular genetic data. The modern diagnostic process is moving
from quantitative morphological assessment to multiparameter flow cytometry (MFC) for cell lineage determination and specific phenotypes such as ETP-ALL. ICC 2022 expands the taxonomy with nine new categories based on gene rearrangements and specific mutations, including a detailed distinction between Ph-positive subtypes (ALL-L and ALL-M). Prognosis is assessed by combining static clinical factors (age, WBC, extramedullary involvement) and genetic aberrations.
Particular attention is paid to Ph-like ALL as a powerful predictor for targeted therapy with TKIs or JAK inhibitors. Measurable residual disease (MRD) has been established as the most significant dynamic prognostic marker. While multiparameter flow cytometry achieves a sensitivity of 10-5, next-generation sequencing (NGS) allows detection of up to 10-6, defining the concept of “deep molecular remission”.
Integrated risk-adapted therapy systems (such as COG and BFM) use MRD status at key time points to refine treatment. The future of diagnostics is directed towards standardizing ultrasensitive methods with the aim of optimizing therapeutic response and preventing relapse.

Key words: Acute lymphoblastic leukemia (ALL), ICC 2022, risk stratification, measurable residual disease (MRD), Ph-like ALL, NGS.

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Address for correspondence::

Dr. H. Burnusuzov

Department of Pediatrics, University Hospital “Pulmed” – Plovdiv
1A, Perushtitsa, Str.

4002, Plovdiv

e-mail: hassan_md@abv.bg