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2495 A Double Blind Randomised Clinical Trial to Prevent Serious Side Effects of Dexamethasone during Pediatric Acute Lymphoblastic Leukemia Treatment

Acute Lymphoblastic Leukemia: Clinical Studies
Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster II
Sunday, December 6, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Lidewij T Warris, MD1,2*, Marry M van den Heuvel-Eibrink, MD, PhD1,3, Femke K Aarsen, MSc PhD1*, Saskia MF Pluijm4*, Marc B Bierings, MD PhD5, Cor van den Bos, MD PhD6*, Christian M. Zwaan, MD, PhD1, Wim JE Tissing, MD, PhD7*, Margreet A Veening, MD8*, Rob Pieters, MD, PhD3,9 and Erica LT van den Akker, MD PhD2*

1Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
2Department of Pediatric Endocrinology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
3Princess Máxima Centre for Pediatric Oncology, Utrecht, Netherlands
4Department of Paediatric Oncology/Hematology, Erasmus MC-Sophia’s Children’s Hospital, Rotterdam, Netherlands
5Department of Hematology and Immunology, Wilhelmina Children's Hospital, Utrecht, Netherlands
6Department of Pediatric Oncology, Academic Medical Center, Amsterdam, Netherlands
7Department of Paediatric Oncology, University Medical Center Groningen, Groningen, Netherlands
8Department of Pediatric Oncology, VU medical center, Amsterdam, Netherlands
9Department of Pediatric Oncology/Hematology, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands

Background/ Objectives: Dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious metabolic and neuropsychological side effects. Recent studies have led to the hypothesis that neuropsychological side effects could be due to cortisol depletion of the cerebral mineralocorticoid receptor. We therefore studied whether adding a physiological dose of hydrocortisone to dexamethasone treatment reduces neuropsychological and metabolic side effects in children with ALL.

Design/ Methods: We performed a multicentre double-blind, randomised controlled trial with a crossover design. Patients (3-16 years) treated with dexamethasone pulses according to the DCOG ALL protocols were included. Patients received hydrocortisone 10 mg/m2/day in a circadian rhythm during one dexamethasone course and placebo during another dexamethasone course in a randomised order. The primary outcome measures were mood and behavior (parent-reported Strenght and Difficulties Questionnaire- Dut (SDQ)). Secondary outcome measures included sleep (Sleep Disturbance Scale for Children (SDSC)), neurocognitive function, and metabolic parameters.

Results: 50 subjects were enrolled, of which 48 patients completed both courses. For the total group no significant effects were found. However, in the subgroup of children with clinically significant behavioral side effects, adding hydrocortisone resulted in a significant reduction of side effects on overall stress (-4.9 (=0.9 SD), P=0.00), mood (-1.8 (=0.9 SD), P=0.03), behavior (-1.0 (=0.7 SD), P=0.01), and impact (P<0.05). The subgroup with dexamethasone-related sleeping problems did benefit on total sleeping problems (-4.3, P<0.05). In contrast, hydrocortisone addition did not affect metabolic parameters.

Conclusion: This randomised controlled trial provides evidence that addition of a physiological dose of hydrocortisone in circadian rhythm during dexamethasone treatment in pediatric ALL patients reduces side effects on behavior, mood and sleep. This novel and simple intervention may be valuable for all patients on high-dose dexamethasone treatment.

Disclosures: No relevant conflicts of interest to declare.

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