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Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia. J Clin Oncol 2001 Feb 15;19(4):1040-6

Date

02/22/2001

Pubmed ID

11181667

DOI

10.1200/JCO.2001.19.4.1040

Scopus ID

2-s2.0-0035865159   52 Citations

Abstract

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 mg/m(2)/d) administered as a 3-day, single-drug window before initiation of standard, multidrug induction chemotherapy. Corticosteroid drug response was measured by reduction in bone marrow blast counts and absolute peripheral blast counts after 3 days. Glucocorticoid receptor (GCR) number and the effective concentration of dexamethasone resulting in a 50% reduction of leukemic cell viability in vitro (EC-50) were evaluated at days 0 and 3.

RESULTS: Increasing dexamethasone doses resulted in greater marrow blast response (P =.007), with a similar trend in peripheral-blood blast response. High-dose corticosteroid regimens (dexamethasone 18 or 150 mg/m(2)/d) elicited better responses than standard doses of dexamethasone or prednisone (bone marrow, P =.002; peripheral blasts, P =.05). Among patients treated with standard-dose corticosteroids, 38% with resistant (EC-50 > 10(-7)) peripheral blasts had a good response compared with 92% with sensitive (EC-50 < 10(-7)) peripheral blasts (P =.01). In contrast, there was no differential response according to EC-50 group after high-dose corticosteroids. Similarly, an association between response and GCR on peripheral-blood blasts was noted after standard-dose corticosteroid regimens but not after high-dose corticosteroid regimens.

CONCLUSION: Response of ALL to glucocorticoid therapy increased with dose. Higher-dose corticosteroid treatment abrogated the effect of relative drug insensitivity and of low GCR on peripheral blasts.

Author List

Schwartz CL, Thompson EB, Gelber RD, Young ML, Chilton D, Cohen HJ, Sallan SE

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Blood Cell Count
Bone Marrow Cells
Child
Child, Preschool
Dexamethasone
Dose-Response Relationship, Drug
Female
Humans
Infant
Infant, Newborn
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prednisolone
Treatment Outcome
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab