Petersen 2003.

Methods	Study type: prospective single‐centre study Setting: University Hospital, Rigshospitalet, Copenhagen, Denmark
Participants	17 children (median age at diagnosis 5.4 years (range 2 to 15 years)) with ALL
Interventions	According to risk groups by NOPHO ALL‐1992 or ALL‐2000 protocol. Ten children were studied after receiving prednisolone, weekly vincristine, 4 doses of IT methotrexate, L‐asparaginase, and doxorubicin. Seven additional children were studied following reinduction therapy with dexamethasone, weekly vincristine and daunorubicin, 4 doses of L‐asparaginase, and IT methotrexate. Type of glucocorticoid therapy: induction phase (n = 10): prednisolone (60 mg/m2/d, in 3 daily doses) during first 5 weeks of induction therapy followed by 9 days of tapering 1‐Week courses of prednisolone (60 mg/m2/d, based on additional information provided by trial authors) were administered every 4 to 10 weeks as part of reinduction therapy, beginning approximately 8 weeks after prednisolone. Reinduction therapy (n = 7): dexamethasone (10 mg/m2/d, divided into 3 daily doses) for 3 weeks on protocol days 169 to 190 (4 intermediate‐risk patients) or days 246 to 267 (3 high‐risk patients) followed by 9 days of tapering. High‐risk patients received two 1‐week courses of prednisolone (40 mg/m2/d) 4 and 8 weeks before dexamethasone therapy. One‐week courses of prednisolone (60 mg/m2/d) were administered every 4 to 10 weeks as part of reinduction therapy, beginning approximately 11 weeks after dexamethasone therapy. Cumulative dose: induction therapy: 2100 mg/m2 + 157.5 mg/m2 prednisolone. One child received an additional 840 mg/m2 prednisolone during the period of adrenal insufficiency. Reinduction therapy: 210 mg/m2 + 26.5 mg/m2 dexamethasone. High‐risk patients received 560 mg/m2 prednisolone in advance; 1 high‐risk patient received an additional 420 mg/m2 prednisolone during period of adrenal insufficiency, and 2 high‐risk patients received an additional 1260 mg/m2 prednisolone during period of adrenal insufficiency. Duration of glucocorticoid therapy: induction therapy: 35 days of prednisolone + 9 days tapering doses. One child received an additional 14 days of prednisolone. Reinduction therapy: 21 days of dexamethasone + 9 days tapering doses. High‐risk patients received 14 days of prednisolone 4 and 8 weeks before dexamethasone therapy. After the dexamethasone course, high‐risk patients also received prednisolone for 1 week (n = 1) or 3 weeks (n = 2). Methods of cessation of glucocorticoid therapy: 50% each 3 days, over 9 days in total No control intervention
Outcomes	Specific HPA axis function test: ACTH stimulation test (250 µg tetracosactide (Synacthen, Novartis)) between 8 and 11 a.m. (basal cortisol and after 30 and 60 minutes) Moment of testing: Adrenal function was assessed by an ACTH stimulation test within 2 weeks after discontinuation of glucocorticoid therapy. Testing was repeated every 3 to 5 weeks until recovery or end of follow‐up. Tests were performed during treatment for ALL. Cutoff limits defined by original studies: low‐dose ACTH test: normal response > 500 nmol/L Fluconazole therapy was evaluated as a risk factor for adrenal insufficiency.
Notes	0 children were lost to follow‐up. Length of follow‐up after glucocorticoid therapy: fluctuating Funding source: not mentioned Declaration of interest among primary researchers: not mentioned