Systematic Light Exposure Effects on Circadian Rhythms Entrainment, Inflammation, Neutropenic Fever and Symptom Burden among Multiple Myeloma Patients undergoing Autologous Stem Cell Transplantation

项目总结 多发性骨髓瘤患者接受自体干细胞移植(ASCT) 有过影响疾病预后、存活率的临床显著负面后遗症 生活质量。这些后遗症包括促炎细胞因子的产生增加， 中性粒细胞减少性发热的发生率更高，症状负担更重(如抑郁、疼痛) 它们与昼夜节律紊乱(CRD)有关。CRD涉及到 自然发生的激素分泌、温度和活动的24小时循环。CRD加薪 促炎细胞因子的产生引发了一系列负面影响，包括 更高的症状负担和发展为中性粒细胞减少症的风险。CRD已关联 预后和存活率较差。我们最近完成的R21研究显示，那天早上 患者病房的昼夜有效照明导致显著更高的 夜间褪黑激素水平、抑郁症减少和炎性细胞因子的产生 与昼夜节律无效的组(对照组)相比。在积极小组中，在 观察睡眠情况和中性粒细胞减少的情况。我们的R21结果也显示出强劲的 褪黑素水平与促炎细胞因子呈负相关。因此，对于 建议的多点随机对照试验(RCT)我们假设昼夜节律 早晨暴露在阳光下会导致更好的睡眠，更低的促肾上腺皮质激素水平 炎性细胞因子和症状负担，以及中性粒细胞减少的发生 发烧。我们将调查患者的病房/门诊是否有昼夜有效的照明 在ASCT期间的设置，促进昼夜节律携带和改善睡眠，如果昼夜节律 夹带可减少炎症。我们还将调查是否有更好的夹带和 促炎标志物水平较低与中性粒细胞减少的发生有关 发烧，减轻症状负担。昼夜节律刺激灯将安装在 门诊室/病房，因为移植是在两个环境中进行的。独一无二的 我们介入的好处是它不需要任何病人的努力，因为昼夜节律- 整个房间都有主动光投射。 该项目将确定：1)昼夜节律有效光与昼夜无效光相比， 在ASCT期间给药导致昼夜节律缠绕；2)昼夜节律缠绕 减少促炎细胞因子并介导昼夜效应光对血管内皮细胞的影响 细胞因子；以及3)炎性细胞因子水平降低与减少有关 患者出现中性粒细胞减少热，症状负担降低。

PROJECT SUMMARY Multiple Myeloma (MM) patients undergoing Autologous Stem Cell Transplantation (ASCT) experience clinically significant negative sequelae affecting disease prognosis, survival, and quality of life. These sequelae include increase in production of pro-inflammatory cytokines, higher occurrences of neutropenic fever and higher symptom burden (e.g., depression, pain) which are associated with circadian rhythm disruption (CRD). CRD involves disruption in naturally occurring 24-hour cycles of hormone secretion, temperature and activity. CRD raises production of pro-inflammatory cytokines unfolding a cascade of negative effects that include higher symptom burden and risk of developing neutropenic fever. CRD has been associated with poorer prognosis and survival. Our recently completed R21 study showed that morning circadian-effective illumination of patients' hospital rooms resulted in significantly higher nocturnal melatonin levels, reduced depression and production of inflammatory cytokines compared to the circadian-ineffective group (control). In the active group, an improvement in sleep and reduction in neutropenic fever was observed. Our R21 results also showed a strong negative relationship between melatonin levels and pro-inflammatory cytokines. Therefore, for the proposed multi-site randomized controlled trial (RCT) we hypothesize that circadian entrainment resulting from morning light exposure will lead to better sleep, lower levels of pro- inflammatory cytokines and symptom burden, as well as fewer occurrences of neutropenic fever. We will investigate if circadian-effective illumination, of patients' hospital rooms/outpatient settings during ASCT, promotes circadian entrainment and improves sleep, and if circadian entrainment reduces inflammation. We will also investigate whether better entrainment and lower levels of pro-inflammatory markers are associated with fewer occurrences of neutropenic fever and reduced symptom burden. The circadian stimulating light will be installed in the outpatient setting/hospital rooms since transplants are performed in both settings. A unique advantage of our intervention is that it does not require any patient effort because the circadian- active light is delivered throughout the entire room. The project will determine if: 1) circadian-effective light compared to circadian-ineffective light, delivered during ASCT results in circadian rhythm entrainment; 2) circadian entrainment reduces pro-inflammation cytokines and mediates the effects of circadian-effective light on the cytokines; and 3) reduced levels of inflammatory cytokines are associated with reduced occurrence of neutropenic fever and lower symptom burden in patients.