DexaDagen-2 study

INTERVENTION: The intervention consists of 4 identical dexamethasone courses (duration 5 days), during which patients will receive addition of either hydrocortisone (2 consecutive courses) or placebo (2 consecutive courses). Patients will be randomized and cross over will take place after 2 courses. CONDITION: Acute Lymphoblastic Leukemia , Dexamethasone, Hydrocortisone ; ; PRIMARY OUTCOME: Neurobehavioral problems after 5 days of dexamethasone treatment with or without hydrocortisone addition. These neurobehavioral problems will be measured with the parent‐reported SDQ. SECONDARY OUTCOME: ‐ Dexamethasone related sleeping difficulties after 5 days of dexamethasone treatment with or without hydrocortisone, measured by the Sleep Disturbance Scale for Children (SDSC) and actigraphy. ; ; ‐ Quality of life after 5 days of dexamethasone treatment with or without hydrocortisone addition, measured with the Pediatric Quality of Life questionnaire (PedsQL). ; ; ‐ The prevalence of frailty and the influence of 5 days of dexamethasone on the different frailty parameters, measured through actigraphy, bio‐impedance, ultrasonography, Timed ‘Up and Go’ test, activity questionnaire and handgrip strength. ; ; ; ; Furthermore we will study possible factors influencing the inter‐patient variability in developing neurobehavioral side effects: ; ; ‐ Dexamethasone kinetics (i.e. trough and peak levels) and the effect on the development of dexamethasone induced clinically relevant neurobehavioral and sleeping problems. ; ; ‐ Carrier status of candidate single nucleotide polymorphisms (SNPs) and the influence on the development of dexamethasone induced clinically relevant neurobehavioral problems. ; ; ‐ Psychosocial and environmental factors (measured through several questionnaires) that potentially determine the development of dexamethasone induced clinically relevant neurobehavioral problems. INCLUSION CRITERIA: ‐ Written informed consent ‐ Age 3‐18 ‐ Confirmed diagnosis of acute lymphoblastic leukemia (ALL) ‐ Inclusion in DCOG ALL medium risk group protocol ‐ Able to comply with scheduled follow‐up