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

项目摘要 接受自体干细胞移植（ASCT）的多发性骨髓瘤（MM）患者 出现影响疾病预后、生存率的具有临床意义的负面后遗症，以及 生活质量这些后遗症包括促炎细胞因子的产生增加， 更高的血小板减少性发热发生率和更高的症状负担（例如，抑郁、疼痛） 这与昼夜节律紊乱（CRD）有关。CRD涉及中断 自然发生的激素分泌，温度和活动的24小时周期。CRD提高 促炎细胞因子的产生会引发一连串的负面影响，包括 更高的症状负担和发展为血小板减少性发热的风险。CRD已经与 预后和生存率都较差。我们最近完成的R21研究显示， 病人病房的昼夜有效照明， 夜间褪黑激素水平，减少抑郁和炎症细胞因子的产生 与昼夜节律无效组（对照组）相比。在活动组中， 观察到睡眠和血小板减少性发热减少。我们的R21结果也显示了一个强大的 褪黑激素水平与促炎细胞因子之间呈负相关。因此对于 在拟议的多中心随机对照试验（RCT）中，我们假设昼夜节律 晨间阳光照射导致的夹带将导致更好的睡眠，更低的亲， 炎性细胞因子和症状负担，以及更少的血小板减少症的发生， 发烧我们将调查患者病房/门诊的昼夜有效照明 ASCT期间的设置，促进昼夜节律夹带和改善睡眠，如果昼夜节律 夹带减少炎症。我们还将研究是否更好的夹带和 促炎性标志物水平较低， 发热和减轻症状负担。昼夜节律刺激灯将安装在 门诊部/医院病房，因为移植在这两种环境中进行。一个独特 我们的干预的优点是，它不需要任何病人的努力，因为昼夜节律- 主动光被传递到整个房间。 该项目将确定：1）昼夜有效光与昼夜无效光相比， 在ASCT期间递送导致昼夜节律夹带; 2）昼夜节律夹带 减少促炎细胞因子，并介导昼夜节律有效光对 细胞因子;和3）炎性细胞因子水平的降低与炎性细胞因子水平的降低相关。 减少患者的贫血性发热和症状负担。

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.