Lighting for Circadian Entrainment in Myeloma Transplant Patients

By Mariana G. Figueiro, Ph.D., Professor and Director, Light and Health Research Center

The survival of virtually any organism depends on a complex system of internally generated, repeating physiological processes called circadian rhythms. In humans, these rhythms cycle at a period of roughly (but not exactly) 24 hours and include processes such as sleeping and waking, hormone production (e.g., melatonin and cortisol), core body temperature, and digestion, just to name a few. The pattern of light and dark on the retina is the principal environmental cue for synchronizing human circadian rhythms to our local position on Earth, ensuring our body does the right things at the right times of day and night. Disruption of these rhythms by light at night and insufficient daytime light exposures has been linked to poor sleep and a host of health and behavioral problems.

Patients with multiple myeloma—a cancer that forms in plasma cells and accumulates in bone marrow, crowding out healthy blood cells that fight infection—spend 2–3 weeks in hospital rooms while undergoing autologous stem cell transplantation to combat the disease. The healthcare environment’s typically low daytime light levels and frequent exposures to light at night can lead to circadian disruption and compromise patients’ recovery. To address these concerns, the Light and Health Research Center (LHRC) and collaborators (William Redd and Heiðdís Valdimarsdottir), under funding from the National Cancer Institute, conducted peer-reviewed pilot research to determine whether administering circadian-effective light early in the day could maintain multiple myeloma patients’ alignment with the day-night cycle, as indicated by high nighttime melatonin levels and good sleep quality.

Fifty-five patients were randomly assigned to two lighting conditions, providing either circadian-effective light (n=27) or circadian-ineffective light (n=28) in their hospital rooms between 7 and 10 a.m. each day. The circadian-effective light treatment was specified following the circadian stimulus (CS) model developed by LHRC researchers over the past 20 years.(1-4) For this study, the circadian effective light was specified to a criterion CS value of 0.3, which has been shown in field studies to improve sleep in other populations.(5-7) (Readers are encouraged to explore the LHRC’s freely available web-based CS Calculator.)

The Lighting

Acuity Brands developed the study’s custom-made freestanding 3000K luminaires (Figure 1), which were used to deliver either the circadian-effective bright white light (BWL) condition (ranging between 1000 lx and 1300 lx, CS = 0.3) or the circadian-ineffective dim white light (DWL) condition (about 90 lx, CS = 0.1), measured at the patient beds’ pillow surface. The CCT of 3000K was chosen to make the rooms’ appearance less institutional and more homelike, and the ambient lighting form factor was selected over light boxes to reduce patients’ compliance burden. CS levels were continuously monitored on the wall behind each bed, on each luminaire, and at each patients’ chest level using three separate Daysimeters (calibrated light meters developed by LHRC researchers(8, 9)). The measurements showed that patients in the BWL condition received significantly (p < 0.001) higher CS values than those in the DWL condition.

Figure 1: The typical position of the experimental luminaire in a patient room. Daysimeters were positioned on the wall behind the head of the patient bed, on the luminaire, and on the patient’s chest as a pendant.

Study Results

Sleep quality and depression scores were assessed prior to hospitalization, on post-transplant days two and seven, and on post-engraftment day three (i.e., after the body accepts the transplanted stem cells, typically the day before discharge from the hospital). Nighttime melatonin levels were assessed prior to hospitalization and post engraftment. Sleep quality was assessed using wrist-worn devices that measure activity and light. Depression scores were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). Nighttime melatonin levels were assessed via the measured concentrations of creatinine-corrected urinary melatonin-sulfate (6-sulfatoxymelatonin, or 6-SMT) in the patients’ first morning void urine samples.

Patients’ sleep time in the BWL condition steadily improved over the course of the study, whereas those in the DWL condition slept for shorter durations by the study’s end compared to the beginning (Figure 2A). Depression scores, obtained in an earlier, peer-reviewed iteration of this study(10) involving fewer patients (BWL = 23 patients, DWL = 21 patients), but retaining the strong statistical effect, were also significantly better among those experiencing the BWL condition compared to those in the DWL condition (Figure 2B).

Figure 2. (A) Mean sleep time (in minutes) throughout the study’s four assessment days for the two light conditions. Although not statistically significant, sleep duration at the end of hospitalization increased by over 50 minutes in the BWL group compared to the DWL group. (B) Depression (CES‐D) scores throughout the study’s four assessment days for the two light conditions. Mean depressive symptoms increased for both groups, but only the mean score for patients in the DWL condition met the criteria for clinically significant depression. The data presented in panel B were reported in Valdimarsdottir et al.(10)

Patients’ nighttime melatonin levels in the DWL condition declined compared to their pre-hospitalization levels. The levels among patients in the BWL condition remained almost constant, suggesting that their circadian rhythms remained aligned following their admission and treatment (Figure 3).

Figure 3. The mean difference between pre-hospitalization and post-treatment nighttime melatonin levels for the two conditions (6-SMT per ng/ng creatinine). The positive difference means that melatonin levels after hospitalization were significantly decreased in the patients receiving DWL, while they remained stable in the patients that received BWL, reinforcing the suggestion that circadian alignment was better maintained in patients who experienced the BWL condition.

Discussion

Our study suggests that implementing a robust, appropriately timed pattern of light and dark in hospital rooms can maintain patients’ circadian alignment, which leads to better sleep. Given that good sleep has been linked to a series of health benefits, this approach represents an important first step for improving health in hospitalized patients, especially among those in longer term recovery from procedures like autologous stem cell transplantation.

These results should be interpreted in the context of some important limitations, the principal ones being the study’s preliminary nature and small sample size. Also, because the results do not include post-hospitalization assessments, it cannot be said whether the circadian-effective light delivered during hospitalization affected primary disease outcomes during the extended post-transplant period. We have just been awarded a large grant from the National Cancer Institute to perform, together with Memorial Sloan Kettering Cancer Center in NYC, a clinical trial that will extend these preliminary results while also measuring immune function biomarkers and patients’ symptom burden.

Despite these limitations, our findings demonstrate that this easy-to-deliver, lowcost intervention nonetheless improves sleep quality during hospitalization for autologous stem cell transplantation patients.

In our next column, we will outline possible design strategies for implementing a comprehensive lighting regime in hospital rooms to promote patient recovery and general well-being. ■

References Cited

1. Rea MS, Figueiro MG, Bullough JD, Bierman A. A model of phototransduction by the human circadian system. Brain Research Reviews. 2005; 50: 213-228.2. Rea MS, Figueiro MG, Bierman A, Bullough JD. Circadian light. Journal of Circadian Rhythms. 2010; 8: 2.3. Rea MS, Nagare R, Figueiro MG. Modeling circadian phototransduction: Retinal neurophysiology and neuroanatomy. Frontiers in Neuroscience. 2021; 14: 1467.4. Rea MS, Nagare R, Figueiro MG. Modeling circadian phototransduction: Quantitative predictions of psychophysical data. Frontiers in Neuroscience. 2021; 15: 44.

5. Figueiro MG, Kalsher M, Steverson BC, Heerwagen J, Kampschroer K, Rea MS. Circadian-effective light and its impact on alertness in office workers. Lighting Research & Technology. 2019; 51: 171-183.

6. Figueiro MG, Plitnick B, Roohan C, Sahin L, Kalsher M, Rea MS. Effects of a tailored lighting intervention on sleep quality, rest–activity, mood, and behavior in older adults with Alzheimer’s disease and related dementias: A randomized clinical trial. Journal of Clinical Sleep Medicine. 2019; 15: 1757-1767.

7. Figueiro MG, Sahin L, Kalsher M, Plitnick B, Rea MS. Long-term, all-day exposure to circadian-effective light improves sleep, mood, and behavior in persons with dementia. Journal of Alzheimer's Disease Reports. 2020; 4: 297-312.

8. Bierman A, Klein TR, Rea MS. The Daysimeter: A device for measuring optical radiation as a stimulus for the human circadian system. Measurement Science and Technology. 2005; 16: 2292-2299.

9. Figueiro MG, Hamner R, Bierman A, Rea MS. Comparisons of three practical field devices used to measure personal light exposures and activity levels. Lighting Research & Technology. 2013; 45: 421-434.

10. Valdimarsdottir HB, Figueiro MG, Holden W, Lutgendorf S, Wu LM, Ancoli‐Israel S, et al. Programmed environmental illumination during autologous stem cell transplantation hospitalization for the treatment of multiple myeloma reduces severity of depression: A preliminary randomized controlled trial. Cancer Medicine. 2018; 7: 4345-4353.