Photo by Bill Branson
Adding a physiologic dose of hydrocortisone to treatment with dexamethasone can reduce the severity of certain adverse effects (AEs) in pediatric patients with acute lymphoblastic leukemia (ALL), according to researchers.
Hydrocortisone did not decrease the incidence of psychosocial problems or sleep-related issues in these patients, but the drug did reduce the severity of these problems among patients who experienced them.
Lidewij T. Warris, MD, of Erasmus MC-Sophia Children’s Hospital in Rotterdam, the Netherlands, and her colleagues reported these results in the Journal of Clinical Oncology.
The team conducted this study to determine whether a physiologic dose of hydrocortisone could reduce neuropsychologic and metabolic AEs in children with ALL who were receiving dexamethasone.
The study enrolled 50 patients (ages 3 to 16) who were set to receive 2 consecutive courses of dexamethasone in accordance with Dutch Childhood Oncology Group ALL protocols.
The patients were randomized to receive either hydrocortisone or placebo in a circadian rhythm (10 mg/m2/d) during their first dexamethasone course. During their second course, the patients were assigned to the opposite arm.
The treatment groups were similar with regard to age, type of leukemia, treatment protocol, and CNS status at diagnosis.
Psychosocial problems
The researchers assessed psychosocial problems by having parents complete the Strength and Difficulties Questionnaire (SDQ). Forty-six parents completed the questionnaire at all 4 time points tested.
The results showed that 4 days of dexamethasone treatment significantly increased patient problems, as reported by all SDQ scales and subscales. However, one-third of the population did not have any increase in SDQ total difficulties with dexamethasone.
The addition of hydrocortisone did not affect patients’ total difficulties score (mean difference, -0.8 ± 5.5; P=0.33), emotional symptoms (mean difference, -0.6 ± 2.3; P=0.08), conduct problems (mean difference, 0.0 ± 1.5; P=1.00), or other SDQ subscales.
However, hydrocortisone did have a clinically significant effect in the subset of 16 patients who had clinically relevant dexamethasone-related AEs. This was defined as an increase of ≥5 in their SDQ total difficulties score.
In these patients, hydrocortisone improved the total difficulties delta-score (median difference, -5.0; IQR, -7.8 to -3.0), emotional symptoms score (median difference, -1.5; IQR, -4.0 to -1.0), conduct problems score (median difference, -1.0; IQR, -2.0 to 0.0), and impact of stress score (median difference, -1.0; IQR, -2.0 to 0.0).
Sleep issues
The researchers used the Sleep Disturbance Scale for Children (SDSC) to assess sleep quality and sleep disturbances. Forty-seven parents completed the questionnaire at all 4 time points tested.
Results showed that dexamethasone significantly increased disorders of arousal (P=0.04), sleep-wake transition disorders (P=0.01), and disorders of excessive somnolence (P=0.01).
The addition of hydrocortisone had no significant effect on patients’ total SDSC score (P=0.84), disorders of initiating and maintaining sleep (P=0.74), disorders of excessive somnolence (P=0.29), or sleep-wake transition disorder (P=0.29).
However, hydrocortisone did have a clinically significant effect in the subset of 9 children who had clinically relevant dexamethasone-induced sleeping problems, which were defined as a change of ≥7 in SDSC total score.
Hydrocortisone reduced SDSC total scores (median difference, -11.0; IQR, -16.0 to 0.0) and disorders of initiating and maintaining sleep scores (median difference, -3.0; IQR, -7.0 to –0.5).
Other outcomes
The researchers also found that dexamethasone treatment alone did not affect patients’ attention, visual-spatial functions, memory, or processing speed.
However, the addition of hydrocortisone significantly improved patients’ long-term visual memory (P=0.01).
Hydrocortisone did not have any effect on other neuropsychological tests or on metabolic parameters.
