253 General discussion 8 Measurements Main findings Intervention Oral hydrocortisone (10mg/m2/day in circadian rhythm) compared to placebo Outcomes - Behavior: SDQ questionnaire - Sleep: actigraphy and SDSC questionnaire - Hunger: four VAS scores - Quality of Life: PedsQL questionnaire - Parental stress: DT-P - Compared to placebo, hydrocortisone had no additional beneficial effect in reducing clinically relevant dexamethasone-induced neurobehavioral problems. - Hydrocortisone did not improve sleep, quality of life or parental stress. - Hydrocortisone led to an increased average and fasting hunger score compared to placebo. - Placebo and nocebo effects may play an important role in behavioral side effects. Cell lines - Cytotoxicity of dexamethasone, prednisolone and hydrocortisone - Transcriptional activity PDX / patient samples - Cytotoxicity of dexamethasone, prednisolone and hydrocortisone, combined with RU28318 (MR antagonist) ALL patients - MR and GR expression levels - Prednisone response - Outcome (survival / events) - Hydrocortisone can induce the expression of steroidregulated genes via both the GR and the MR. - Dexamethasone predominantly induces transcription via the GR. - Hydrocortisone can induce significant steroid-induced cell death by activation of the MR or the GR. - Dexamethasone induces significant steroid-induced cell death via the GR, but also via the MR. - The MR is potentially capable of inducing leukemic cell death after activation by steroid treatment. - Relative expression of the GR is higher than the MR in ALL patients - The role of the MR in steroid-induced cytotoxicity is limited in ALL patients PDX: patient derived xenograft, RCT: randomized clinical trial, SDS: standardized deviation score, SDSC: sleep disturbance scale for children, SDQ: strengths and difficulties questionnaire, SNP: single nucleotide polymorphism, VAS: visual analogue scale
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