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

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.