Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia. (October 2016)

• Record Type: Journal Article
• Authors: Warris, Lidewij T.; van den Akker, Erica L.T.; Aarsen, Femke K.; Bierings, Marc B.; van den Bos, Cor; Tissing, Wim J.E.; Sassen, Sebastiaan D.T.; Veening, Margreet A.; Zwaan, Christian M.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.
• Is Part Of: Psychoneuroendocrinology. Volume 72(2016:Oct.)
• Page Start: 190
• Page End: 195
• Publication Date: 2016-10
• Subjects: Acute lymphoblastic leukemia -- Pediatrics -- Dexamethasone -- Dexamethasone suppression test -- Neurobehavioral problems -- Predictors; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2016.07.006
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: There are no predictors of neuropsychological problems of dexamethasone. The very low dose dexamethasone suppression test did not predict these problems. Dexamethasone trough levels did also not influence neuropsychological problems. Patients with glucocorticoid hypersensitivity had more depressive symptoms. The role of glucocorticoid sensitivity in these problems should be unraveled. Abstract: Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3–16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0 nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6 mg/m 2 ), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N = 11), sleeping problems, and/or somnolence (N = 12) ( P < 0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity.