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

IF 2.1 3区医学 Q2 PEDIATRICS Frontiers in Pediatrics Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI:10.3389/fped.2024.1482720

Katarzyna Pawińska-Wąsikowska, Małgorzata Czogała, Karolina Bukowska-Strakova, Marta Surman, Monika Rygielska, Teofila Książek, Beata Sadowska, Agnieszka Pac, Jolanta Skalska-Sadowska, Magdalena Samborska, Jacek Wachowiak, Małgorzata Ciebiera, Radosław Chaber, Renata Tomaszewska, Tomasz Szczepański, Karolina Zielezińska, Tomasz Urasiński, Anna Rodziewicz-Konarska, Krzysztof Kałwak, Marta Kozłowska, Ninela Irga-Jaworska, Barbara Sikorska-Fic, Bartosz Chyżyński, Paweł Łaguna, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Paulina Deleszkiewicz, Katarzyna Drabko, Katarzyna Bobeff, Wojciech Młynarski, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Mycko, Wanda Badowska, Natalia Bartoszewicz, Jan Styczyński, Katarzyna Machnik, Weronika Stolpa, Agnieszka Mizia-Malarz, Walentyna Balwierz, Szymon Skoczeń

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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.

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波兰急性髓性白血病儿童和青少年早期死亡和治疗相关死亡分析：2005-2023 年。

背景：针对儿童和青少年急性髓性白血病（AML）的个性化治疗方法以及支持性疗法的开发，大大提高了患者的生存率。尽管如此，仍有一些患者在开始治疗前死亡，或在获得缓解前的早期治疗阶段死亡。该研究分析了急性髓细胞性白血病儿童和青少年患者早期死亡（ED）和治疗相关死亡（TRD）的频率、临床特征和风险因素：从2005年1月到2023年11月，波兰儿童白血病和淋巴瘤研究小组的中心按照随后的三种治疗方案对646名接受治疗的AML患儿进行了评估：AML-BFM2004年中期方案（385名患儿）、AML-BFM2012年登记方案（131名患儿）和AML-BFM2019年方案（130名患儿）：结果：在646名患儿中，有30名患儿早逝，其中包括15名女孩。中位年龄为 10.7 岁（1 天至 18 岁）。超过一半的患者（53%）被诊断为急性粒单核细胞白血病（M5），13%被诊断为急性早幼粒细胞白血病（M3）。AML-BFM三个连续方案的ED率分别为4.9% vs. 5.3% vs. 3.1%。19名患者在治疗第15天之前死亡，11名患者在治疗第15天至第42天之间死亡。第15天前（ED15）最常见的死亡原因是白细胞增多和出血，而第15天到第42天之间（ED15-42）最常见的死亡原因是感染，主要是细菌性败血症。ED15 与高白细胞计数（>10 × 109/L）、M3 白血病之间存在明显关联（P = 0.029）。在单变量分析中，只有初始高白细胞计数（>100 × 109/L）是早期死亡的重要预测因素。在整个研究期间，总体TRD为3.4%。死亡的主要原因是感染，主要是细菌性败血症（22 名儿童中有 10 名，占 45.4%）：结论：尽管采用了各种细胞吞噬方法，但高白细胞仍是急性髓细胞白血病患者早期死亡的重要因素。感染仍是治疗相关死亡的主要原因。使用新的靶向药物进行更个体化的治疗可能是未来的治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Pediatrics Medicine-Pediatrics, Perinatology and Child Health

CiteScore

3.60

自引率

7.70%

发文量

2132

审稿时长

14 weeks

期刊介绍： Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.