IL-10 and TNFα are associated with decreased survival in low-risk pediatric acute myeloid leukemia; a children's oncology group report.

IF 1.2 4区 医学 Q4 HEMATOLOGY
Pediatric Hematology and Oncology Pub Date : 2023-03-01 Epub Date: 2022-07-15 DOI:10.1080/08880018.2022.2089790
Alexandra M Stevens, Terzah M Horton, Chana L Glasser, Robert B Gerbing, Richard Aplenc, Todd A Alonzo, Michele S Redell
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引用次数: 0

Abstract

Pediatric acute myeloid leukemia (AML) is a devastating disease with a high risk of relapse. Current risk classification designates patients as high or low risk (LR) based on molecular features and therapy response. However, 30% of LR patients still suffer relapse, indicating a need for improvement in risk stratification. Cytokine levels, such as IL-6 and IL-10, have been shown to be prognostic in adult AML but have not been well studied in children. Previously, we reported elevated IL-6 levels in pediatric AML bone marrow to be associated with inferior prognosis. Here, we expanded our investigation to assess cytokine levels in diagnostic peripheral blood plasma (PBP) of pediatric AML patients and determined correlation with outcome. Diagnostic PBP was obtained from 80 patients with LR AML enrolled on the Children's Oncology Group AAML1031 study and normal PBP from 11 controls. Cytokine levels were measured and correlation with clinical outcome was assessed. IL-6, TNFα, MIP-3a, and IL-1β were significantly higher in AML patients versus controls when corrected by the Bonferroni method. Furthermore, elevated TNFα and IL-10 were significantly associated with inferior outcomes. Our data demonstrate that in diagnostic PBP of LR pediatric AML patients, certain cytokine levels are elevated as compared to healthy controls and that elevated TNFα and IL-10 are associated with inferior outcomes, supporting the idea that an abnormal inflammatory state may predict poor outcomes. Studies are needed to determine the mechanisms by which these cytokines impact survival, and to further evaluate their use as prognostic biomarkers in pediatric AML.

IL-10和TNFα与低风险小儿急性髓性白血病存活率下降有关;儿童肿瘤学小组报告。
小儿急性髓性白血病(AML)是一种破坏性疾病,复发风险很高。目前的风险分级根据分子特征和治疗反应将患者分为高风险和低风险(LR)。然而,30% 的 LR 患者仍会复发,这表明需要改进风险分层。IL-6和IL-10等细胞因子水平已被证明对成人急性髓细胞白血病的预后有影响,但对儿童的研究还不够深入。以前,我们曾报道过小儿急性髓细胞白血病骨髓中 IL-6 水平升高与预后不良有关。在此,我们扩大了研究范围,评估了小儿急性髓细胞性白血病患者诊断性外周血血浆(PBP)中的细胞因子水平,并确定了其与预后的相关性。诊断性 PBP 取自参加儿童肿瘤学组 AAML1031 研究的 80 名 LR AML 患者,正常 PBP 取自 11 名对照组。测量了细胞因子水平,并评估了其与临床结果的相关性。经 Bonferroni 方法校正后,AML 患者的 IL-6、TNFα、MIP-3a 和 IL-1β 显著高于对照组。此外,TNFα和IL-10的升高与不良预后明显相关。我们的数据表明,与健康对照组相比,在LR儿科AML患者的诊断性PBP中,某些细胞因子水平会升高,而TNFα和IL-10的升高与不良预后有关,这支持了异常炎症状态可能预示不良预后的观点。需要进行研究以确定这些细胞因子影响生存的机制,并进一步评估它们在小儿急性髓细胞性白血病中作为预后生物标志物的应用。
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来源期刊
CiteScore
2.60
自引率
5.90%
发文量
71
审稿时长
6-12 weeks
期刊介绍: PHO: Pediatric Hematology and Oncology covers all aspects of research and patient management within the area of blood disorders and malignant diseases of childhood. Our goal is to make PHO: Pediatric Hematology and Oncology the premier journal for the international community of clinicians and scientists who together aim to define optimal therapeutic strategies for children and young adults with cancer and blood disorders. The journal supports articles that address research in diverse clinical settings, exceptional case studies/series that add novel insights into pathogenesis and/or clinical care, and reviews highlighting discoveries and challenges emerging from consortia and conferences. Clinical studies as well as basic and translational research reports regarding cancer pathogenesis, genetics, molecular diagnostics, pharmacology, stem cells, molecular targeting, cellular and immune therapies and transplantation are of interest. Papers with a focus on supportive care, late effects and on related ethical, legal, psychological, social, cultural, or historical aspects of these fields are also appreciated. Reviews on important developments in the field are welcome. Articles from scientists and clinicians across the international community of Pediatric Hematology and Oncology are considered for publication. The journal is not dependent on or connected with any organization or society. All submissions undergo rigorous peer review prior to publication. Our Editorial Board includes experts in Pediatric Hematology and Oncology representing a wide range of academic and geographic diversity.
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