Pawińska-Wąsikowska Katarzyna, Czogała Małgorzata, Bukowska-Strakova Karolina, Surman Marta, Rygielska Monika, Książek Teofila, Sadowska Beata, Pac Agnieszka, Skalska-Sadowska Jolanta, Samborska Magdalena, Wachowiak Jacek, Ciebiera Małgorzata, Chaber Radosław, Tomaszewska Renata, Szczepański Tomasz, Zielezińska Karolina, Urasiński Tomasz, Rodziewicz-Konarska Anna, Kałwak Krzysztof, Kozłowska Marta, Irga-Jaworska Ninela, Sikorska-Fic Barbara, Chyżyński Bartosz, Łaguna Paweł, Muszyńska-Rosłan Katarzyna, Krawczuk-Rybak Maryna, Deleszkiewicz Paulina, Drabko Katarzyna, Bobeff Katarzyna, Młynarski Wojciech, Chodała-Grzywacz Agnieszka, Karolczyk Grażyna, Mycko Katarzyna, Badowska Wanda, Bartoszewicz Natalia, Styczyński Jan, Machnik Katarzyna, Stolpa Weronika, Mizia-Malarz Agnieszka, Balwierz Walentyna, Skoczeń Szymon
Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
Department of Pediatric Oncology and Hematology, University Children Hospital of Krakow, Krakow, Poland.
Front Pediatr. 2024 Oct 17;12:1482720. doi: 10.3389/fped.2024.1482720. eCollection 2024.
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.
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).
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 × 10/L), M3 leukemia ( < 0.001), and ED15-42 and age <1 year ( = 0.029). In the univariate analysis only initial high leukocyte count >100 × 10/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%).
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.
针对儿童和青少年急性髓系白血病（AML）的个性化治疗方法以及支持性疗法的发展显著提高了生存率。尽管如此，一些患者仍在开始治疗前或治疗早期未达到缓解时死亡。本研究分析了AML儿童和青少年早期死亡（ED）和治疗相关死亡（TRD）的发生率、临床特征及危险因素。
2005年1月至2023年11月，对波兰儿童白血病和淋巴瘤研究组各中心按照三个后续治疗方案治疗的646例AML儿童进行了评估：AML-BFM 2004临时方案（385例儿童）、AML-BFM 2012登记方案（131例儿童）和AML-BFM 2019方案（130例儿童）。
646例儿童中，30例发生早期死亡，其中15例为女孩。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%为急性早幼粒细胞白血病（M3）。连续三个AML-BFM方案的早期死亡率分别为4.9%、5.3%和3.1%。19例患者在治疗第15天前死亡，11例在第15天至42天之间死亡。第15天前（ED15）最常见的死亡原因是白细胞淤滞和出血，而在第15天至第42天之间（ED15-42），主要是细菌败血症感染。发现ED15与高白细胞计数（>10×10⁹/L）、M3白血病（P<0.001）以及ED15-42与年龄<1岁（P=0.029）之间存在显著关联。单因素分析中，仅初始高白细胞计数>100×10⁹/L是早期死亡的显著预测因素。整个研究期间的总体治疗相关死亡率为3.4%。主要死亡原因是感染，主要是细菌败血症（22例中有10例，45.4%）。
尽管采用了各种细胞减灭方法，但高白细胞血症仍是AML患者早期死亡的重要因素。感染仍然是治疗相关死亡的主要原因。未来，使用新型靶向药物的更个体化治疗方法可能是首选的治疗选择。
