Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia

Purpose: We investigated whether there was a dose-response relationship for the use of corticosteroids in childhood acute lymphoblastic leukemia (ALL) . Patients and Methods: Three hundred sixty-nine patients, ages 1 to 18 years with ALL, were randomly assigned to receive one of four different doses of corticosteroid (prednisolone 40 mg/m(2)/d or dexamethasone 6, 18, or 150 m g/m(2)/d) administered as a 3-day, single-drug window before initiation of standard, multidrug induction chemotherapy. Corticosteroid drug response wa s measured by reduction in bone marrow blast counts and absolute peripheral blast counts after 3 days. Glucocarticoid receptor (GCR) number and the ef fective concentration of dexamethasone resulting in a 50% reduction of leuk emic cell viability in vitro (EC-50) were evaluated at days 0 and 3. Results: Increasing dexamethasone doses resulted in greater marrow blast re sponse (P = .007), with a similar trend in peripheral-blood blast response. High-dose carticosteroid regimens (dexamethasone 18 or 150 mg/m2/d) elicit ed better responses than standard doses of dexamethasone or prednisone (bon e marrow, P = .002; peripheral blasts, P = .05). Among patients treated wit h standard-dose corticosteroids, 38% with resistant (EC-50 > 10(-7)) periph eral blasts had a good response compared with 92% with sensitive (EC-50 < 1 0(-7)) peripheral blasts (P = .01). In contrast, there was no differential response according to EC-50 group after high-dose corticosteroids. Similarl y, an association between response and GCR on peripheral-blood blasts was n oted after standard-dose corticosteroid regimens but not after high-dose co rticosteroid regimens. Conclusion: Response of ALL to glucacorticoid therapy increased with dose. Higher-dose corticosteroid treatment abrogated the effect of relative drug insensitivity and of low GCR on peripheral blasts.