Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, North Carolina, United States of America.
Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States of America.
PLoS One. 2022 Jun 14;17(6):e0268963. doi: 10.1371/journal.pone.0268963. eCollection 2022.
Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated with overall survival (OS) and clinical outcomes. We hypothesized that circulating metabolic, inflammatory, and immune molecules have potential as predictive biomarkers for AML patients who receive HCT treatment. This retrospective study was designed with an exploratory approach to comprehensively characterize immune, inflammatory, and metabolomic biomarkers. We identified patients with AML who underwent HCT and had existing baseline plasma samples. Using those samples (n = 34), we studied 65 blood based metabolomic and 61 immune/inflammatory related biomarkers, comparing patients with either long-term OS (≥ 3 years) or short-term OS (OS ≤ 1 years). We also compared the immune/inflammatory response and metabolomic biomarkers in younger vs. older AML patients (≤30 years vs. ≥ 55 years old). In addition, the biomarker profiles were analyzed for their association with clinical outcomes, namely OS, chronic graft versus host disease (cGVHD), acute graft versus host disease (aGVHD), infection and relapse. Several baseline biomarkers were elevated in older versus younger patients, and baseline levels were lower for three markers (IL13, SAA, CRP) in patients with OS ≥ 3 years. We also identified immune/inflammatory response markers associated with aGVHD (IL-9, Eotaxin-3), cGVHD (Flt-1), infection (D-dimer), or relapse (IL-17D, bFGF, Eotaxin-3). Evaluation of metabolic markers demonstrated higher baseline levels of medium- and long-chain acylcarnitines (AC) in older patients, association with aGVHD (lactate, long-chain AC), and cGVHD (medium-chain AC). These differentially expressed profiles merit further evaluation as predictive biomarkers.
尽管造血干细胞移植（HCT）是治疗急性髓系白血病（AML）的唯一治愈方法，但它与重大的治疗相关发病率和死亡率相关。因此，非常需要与总生存期（OS）和临床结果相关的预测生物标志物。我们假设循环代谢、炎症和免疫分子具有作为接受 HCT 治疗的 AML 患者的预测生物标志物的潜力。这项回顾性研究采用探索性方法设计，全面描述免疫、炎症和代谢组学生物标志物。我们确定了接受 HCT 治疗并具有现有基线血浆样本的 AML 患者。使用这些样本（n=34），我们研究了 65 种基于血液的代谢组学和 61 种免疫/炎症相关生物标志物，比较了长期 OS（≥3 年）或短期 OS（OS≤1 年）的患者。我们还比较了年轻 AML 患者（≤30 岁）与老年 AML 患者（≥55 岁）的免疫/炎症反应和代谢组学生物标志物。此外，还分析了生物标志物谱与临床结果（即 OS、慢性移植物抗宿主病（cGVHD）、急性移植物抗宿主病（aGVHD）、感染和复发）的相关性。与年轻患者相比，老年患者的基线标志物水平升高，而 OS≥3 年的患者中三种标志物（IL13、SAA、CRP）的基线水平较低。我们还确定了与 aGVHD（IL-9、Eotaxin-3）、cGVHD（Flt-1）、感染（D-二聚体）或复发（IL-17D、bFGF、Eotaxin-3）相关的免疫/炎症反应标志物。代谢标志物的评估表明，老年患者的基线水平更高中链和长链酰基辅酶 A（AC），与 aGVHD（乳酸、长链 AC）和 cGVHD（中链 AC）相关。这些差异表达谱值得进一步评估作为预测生物标志物。
