Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
Front Immunol. 2024 May 23;15:1377546. doi: 10.3389/fimmu.2024.1377546. eCollection 2024.
Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events.
We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia.
Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414).
Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.
多发性骨髓瘤（MM）是一种常见的血液系统恶性肿瘤，由于患者对化疗的反应和毒性存在差异，因此治疗极具挑战性。本研究旨在探讨治疗前血清白细胞介素 6（IL-6）、白细胞介素 8（IL-8）、单核细胞趋化蛋白 1（MCP-1）和血管内皮生长因子（VEGF）水平对新诊断 MM 患者化疗诱导毒性的预测价值。我们假设这些在肿瘤微环境中起关键作用的细胞因子可能与治疗相关不良事件的发生率和严重程度相关。
我们进行了一项前瞻性观察性研究，纳入了 81 例新诊断的 MM 患者，使用多重流式细胞术检测血清细胞因子水平。研究采用非参数和多变量分析比较了细胞因子水平与化疗诱导的毒性（包括淋巴细胞减少、感染、多发性神经病和中性粒细胞减少）之间的关系。
我们的研究结果表明，细胞因子水平与特定毒性之间存在显著关联。淋巴细胞减少患者的 IL-8 水平较低（p=0.0454），感染或多发性神经病患者的 IL-8 水平较高（p=0.0009 或 p=0.0333）。中性粒细胞减少患者的 VEGF 浓度明显较低（p=0.0343）。IL-8 对感染风险的识别具有 81%的敏感性（AUC=0.69；p=0.0015）。IL-8 是淋巴细胞减少（优势比 [OR]=0.26；95%置信区间 [CI]=0.07-0.78；p=0.0167）和感染（OR=4.76；95% CI=0.07-0.62；p=0.0049）的独立预测因子。高 VEGF 水平与贫血风险增加 4 倍相关（OR=4.13；p=0.0414）。
治疗前血清中 IL-8 和 VEGF 的浓度可预测新诊断 MM 患者化疗后发生血液学并发症、感染和多发性神经病。它们可能成为检测感染、淋巴细胞减少、中性粒细胞减少和治疗相关多发性神经病的简单而有效的生物标志物，有助于化疗方案的个体化和治疗相关风险的降低。
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