Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia.
OBJECTIVE
We investigated whether there was a dose-response relationship for the use of corticosteroids in childhood acute lymphoblastic leukemia (ALL).


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.


CONCLUSIONS
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.
Schwartz
C L
CL
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Thompson
E B
EB
Gelber
R D
RD
Young
M L
ML
Chilton
D
D
Cohen
H J
HJ
Sallan
S E
SE
D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage*; D016896:Treatment Outcome
D003907:Dexamethasone; D011239:Prednisolone