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. 2024 Oct 17:12:1482720.
doi: 10.3389/fped.2024.1482720. eCollection 2024.

Analysis of early and treatment related deaths among children and adolescents with acute myeloid leukemia in Poland: 2005-2023

Katarzyna Pawińska-Wąsikowska  1   2 , Małgorzata Czogała  1   2 , Karolina Bukowska-Strakova  3 , Marta Surman  3 , Monika Rygielska  4 , Teofila Książek  5 , Beata Sadowska  6 , Agnieszka Pac  7 , Jolanta Skalska-Sadowska  8 , Magdalena Samborska  8 , Jacek Wachowiak  8 , Małgorzata Ciebiera  9   10 , Radosław Chaber  9   10 , Renata Tomaszewska  11 , Tomasz Szczepański  11 , Karolina Zielezińska  12 , Tomasz Urasiński  12 , Anna Rodziewicz-Konarska  13 , Krzysztof Kałwak  13 , Marta Kozłowska  14 , Ninela Irga-Jaworska  14 , Barbara Sikorska-Fic  15 , Bartosz Chyżyński  15 , Paweł Łaguna  15 , Katarzyna Muszyńska-Rosłan  16 , Maryna Krawczuk-Rybak  16 , Paulina Deleszkiewicz  17 , Katarzyna Drabko  17 , Katarzyna Bobeff  18 , Wojciech Młynarski  18 , Agnieszka Chodała-Grzywacz  19 , Grażyna Karolczyk  19 , Katarzyna Mycko  20 , Wanda Badowska  20 , Natalia Bartoszewicz  21 , Jan Styczyński  21 , Katarzyna Machnik  22 , Weronika Stolpa  23 , Agnieszka Mizia-Malarz  23 , Walentyna Balwierz  1   2 , Szymon Skoczeń  1   2
Affiliations

Analysis of early and treatment related deaths among children and adolescents with acute myeloid leukemia in Poland: 2005-2023

Katarzyna Pawińska-Wąsikowska et al. Front Pediatr. .

Abstract

Background: A personalised approach to the treatment of acute myeloid leukemia (AML) in children and adolescents, as well as the development of supportive therapies, has significantly improved survival. Despite this, some patients still die before starting treatment or in an early phase of therapy before achieving remission. The study analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment related deaths (TRD) of children and adolescents with AML.

Methods: From January 2005 to November 2023, 646 children with AML treated in the centers of the Polish Pediatric Leukemia and Lymphoma Study Group according to three subsequent therapeutic protocols were evaluated: AML-BFM 2004 Interim (385 children), AML-BFM 2012 Registry (131 children) and AML-BFM 2019 (130 children).

Results: Out of 646 children, early death occurred in 30 children, including 15 girls. The median age was 10.7 years (1 day to 18 years). More than half of the patients (53%) were diagnosed with acute myelomonocytic leukemia (M5) and 13% with acute promyelocytic leukemia (M3). The ED rate for the three consecutive AML-BFM protocols was 4.9% vs. 5.3% vs. 3.1%, respectively. In 19 patients, death occurred before the 15th day of treatment, in 11 between the 15th and 42nd day. The most common cause of death before the 15th day (ED15) was leukostasis and bleeding, whereas between the 15th and 42nd day (ED15-42), infections, mainly bacterial sepsis. A significant association was found between ED15 and high leukocyte count (>10 × 109/L), M3 leukemia (p < 0.001), and ED15-42 and age <1 year (p = 0.029). In the univariate analysis only initial high leukocyte count >100 × 109/L, was a significant predictor of early death. The overall TRD for the entire study period was 3.4%. The main cause of death were infections, mainly bacterial sepsis (10 children out of 22, 45.4%).

Conclusions: Hyperleukocytosis remains significant factor of early mortality in patients with AML, despite the introduction of various cytoreductive methods. Infections are still the main cause of treatment related deaths. A more individualized approach by using new targeted drugs may be the therapeutic option of choice in the future.

Keywords: acute myeloid leukemia; adolescents; children; early death; treatment related death.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

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