Einaudi 2008.

Methods	Study type: multi‐centre RCT Setting: Department of Pediatric Onco‐Hematology, University of Turin, Italy; and Department of Pediatrics, University of Milano‐Bicocca, Hospital of Monza, Italy. This information was based on additional information provided by trial authors.
Participants	64 children (24 who received dexamethasone: mean age at diagnosis 4 years 11 months (range 1 year 2 months to 12 years 1 month), 11 boys and 13 girls; 40 children who received prednisone: mean age at diagnosis 6 years 9 months (range 1 year 2 months to 17 years 6 months), 18 boys and 22 girls) with ALL. This information was based on additional information provided by trial authors.
Interventions	Treatment according to the AIEOP ALL 2000 study. Induction phase 1A: prednisone (from day 8 randomisation prednisone or dexamethasone), vincristine, daunorubicin, Escherichia coli L‐asparaginase, and IT methotrexate. Induction phase 1B: 6‐mercaptopurine, cyclophosphamide, cytosine‐arabinoside, and IT methotrexate Type of glucocorticoid therapy: induction phase: oral prednisone (60 mg/m2/d, divided into 3 daily doses) given on days 1 to 7. On day 8, children were randomised to receive either dexamethasone (10 mg/m2/d) or prednisone (60 mg/m2/d), both divided into 3 oral doses until day 29. From day 30 onwards, the dose of both corticosteroids was tapered by 50% every 3 days until complete withdrawal over 9 days. Cumulative dose of glucocorticoid therapy: prednisone 420 mg/m2 + dexamethasone 246.25 mg/m2 or prednisone 1477.50 mg/m2 Duration of glucocorticoid therapy: prednisone 7 days + dexamethasone 22 days or prednisone 22 days + 9 days tapering doses (in total 39 days) Method of cessation of glucocorticoid therapy: Dose was tapered by 50% every 3 days, until complete withdrawal over 9 days.
Outcomes	Specific HPA axis function test: basal cortisol between 8 and 9 a.m. at diagnosis and low‐dose ACTH test between 8 and 11 a.m. (1 µg/1.74 m2 of tetracosactrin (Synacthen, Novartis, Basel, Switzerland), basal morning value cortisol, after 30 and 60 minutes) Moment of testing: at diagnosis, basal cortisol was determined. The first low‐dose ACTH stimulation test was performed 24 hours after the last tapering dose of glucocorticoid (on day 39), which was given as a single dose in the morning. Tests were performed during treatment for ALL. Cutoff limits defined by original studies: basal cortisol: 6 to 30 µg/dL (167 to 833 nmol/L). Low‐dose ACTH test: normal response ≥ 18 µg/dL (≥ 500 nmol/L) This study addressed type of glucocorticoid as a risk factor.
Notes	0 children were lost to follow‐up. Length of follow‐up after glucocorticoid therapy: Children with suppressed levels underwent further low‐dose ACTH testing between 7 and 14 days from the last glucocorticoid dose and every 2 weeks thereafter until cortisol levels were normalised. Total follow‐up duration was 10 weeks. Funding source: not mentioned Declaration of interest among primary researchers: not mentioned