Dexamethasone Therapy for Acute Lymphoblastic Leukemia Increases Sleep During the Night and During the Day In Young Children
Authors: Harris Anne , Rosen Gerald , Liu Meixia , Krueger James , Messinger Yoav 
Published: October 2019

Abstract
Abstract 258
Dexamethasone (Dex) or prednisone (Pred) are used in Acute Lymphoblastic Leukemia (ALL) therapy. It has long been recognized that dexamethasone effects both daytime behavior and nighttime sleep. The most commonly reported adverse effect of dexamethasone on sleep is sleep onset and sleep maintenance insomnia. An actigraph, recording 24 hours a day for 28 days, was used to evaluate sleep and wakefulness of patients with ALL in maintenance. Patients treated with Dex were evaluated at 3 windows: Dex-on days (1-5), Dex-washout days (6-15) and Dex-off days (16-28). Daytime and nighttime sleep parameters were analyzed from aggregated patient data for all three windows using the median and range. The non-parametric Friedman test was used to compare these parameters over the three windows, and the Wilcoxon Signed Rank Test was used for paired comparisons (used Bonferoni correction). Sleep patterns were also measured using the Childhood Sleep Habit's Questionnaire (CSHQ). The group included 41 ALL patients (29 received Dex, 8 received Pred, and 4 did not receive steroids); 18 females (43.9%), 23 males (56.09%); median age 5 years (range 2 –16). In the Dex treated group, wake during the 5 days of Dex treatment showed less daytime activity mean, greater total daytime sleep minutes, and greater numbers of sleep episodes (>5 minutes) compared to Dex-washout and Dex-off. Sleep during the 5 days of Dex treatment showed: earlier sleep onset time, increased number of sleep minutes, higher sleep efficiency, fewer number of wake episodes (>5 minutes) compared to Dex-washout days (6-15) and Dex-off days (16-28). The effect of dexamethasone on wake and sleep was greatest during the 5 days of treatment, was intermediate during the 10 day washout window and was least during the 13 days at the end of the treatment cycle. This effect was more evident in a subgroup of 28 children treated with Dex who are younger than 10 years old. No significant differences were found for age groups (less than 5 years vs. 5 years or above), gender and steroids (Dex vs. Pred). Interestingly, using the CSHQ 14/23 patients (61%) were identified as poor sleepers with a CSHQ score > 41; mean score for the whole group was 45. CSHQ wake up time strongly correlated with the actigraph data wake up time (r= 0.83). These findings suggest young children with standard risk ALL dexamethasone experience increased sleep both during the day and night. The increase in daytime sleepiness in these children cannot be attributed to nighttime sleep disruption; in fact these children went to sleep earlier and slept with fewer awakenings during dexamethasone treatment. The mechanisms for this change in daytime and nighttime sleep are not understood. Cerebral spinal fluid and plasma cytokines are being measured for these patients to evaluate their role in regulating their sleep.
Table. Comparisons of Actigraph Data between Dex-on, Dex-washout and Dex-off groups Dex – ON (Days 1-5) Dex – Washout (Days 6-15) DEX - Off (Days 16 -28) p-value⋄ p-value* p-value** p-value▴ Sleep related parameters n=29 n=29 n=29 Activity mean 11.2 (6.4, 31.5) 11.1 (6.2, 21.3) 12.6 (5.6, 22.0) 0.639 0.611 0.787 0.417 Sleep minute 521 (363, 668) 493 (376, 618) 500 (359, 584) 0.014 0.001 0.016 0.264 Wake episodes 10 (5, 36) 14.5 (4, 34.5) 19 (3, 39.5) <0.001 0.002 <0.001 0.019 Daytime n=28 n=28 n=28 Activity mean 214 (142, 269) 233 (175, 266) 243 (173, 276) <0.001 <0.001 <0.001 0.004 Sleep min 22.8 (0, 89) 2 (0, 115) 0 (0, 88.5) <0.001 0.002 <0.001 0.031 Sleep Episode 2.3 (0, 8.5) 1 (0, 7) 0 (0, 4) <0.001 0.005 <0.001 0.005 ⋄ Comparison among three groups, Friedman Test * Comparison between Dex On and Dex Washout (Days 6–15), Wilcoxon Signed Ranks Non-parametric Test ** Comparison between Dex ON and Dex OFF (Days 16≂f), Wilcoxon Signed Ranks Non-parametric Test ▴ Comparison between Dex Washout (Day6-15) and Dex OFF (Days 16≂f), Wilcoxon Signed Ranks Non-parametric Test

Disclosures:
No relevant conflicts of interest to declare.