Dexamethasone (6 mg/m2/day) and prednisolone (60 mg/m2/day) were equally effective as induction therapy for childhood acute lymphoblastic leukemia in the EORTC CLG 58951 randomized trial

Abstract

Dexamethasone could be more effective than prednisolone at similar anti-inflammatory doses in the treatment of childhood acute lymphoblastic leukemia. In order to check if this "superiority" of dexamethasone might be dose-dependent, we conducted a randomized phase III trial comparing dexamethasone (6 mg/m(2)/day) to prednisolone (60 mg/m(2)/day) in induction therapy. All newly diagnosed children and adolescents with acute lymphoblastic leukemia in the 58951 EORTC trial were randomized on prephase day 1 or day 8. The main endpoint was event-free survival; secondary endpoints were overall survival and toxicity. A total of 1947 patients with acute lymphoblastic leukemia were randomized. At a median follow-up of 6.9 years, the 8-year event-free survival rate was 81.5% in the dexamethasone arm and 81.2% in the prednisolone arm; the 8-year overall survival rates were 87.2% and 89.0% respectively. The 8-year incidences of isolated or combined central nervous system relapse were 2.9% and 4.5% in the dexamethasone and prednisolone arms, respectively. The incidence of grade 3-4 toxicities during induction and the frequency of osteonecrosis were similar in the two arms. In conclusion, dexamethasone and prednisolone, used respectively at the doses of 6 and 60 mg/m(2)/day during induction, were equally effective and had a similar toxicity profile. Dexamethasone decreased the 8-year central nervous system relapse incidence by 1.6%. This trial was registered at www.clinicaltrials.gov as #NCT00003728.

Figure 1.

General scheme of the EORTC-CLG 58951 trial. IA: induction phase; IB: consolidation phase; II A+B: re-induction and re-consolidation phase; VCR: vincristine; VLR: very low risk (group); AR: average risk (group); VHR: very high risk (group).

Figure 2.

Event-free survival (A) and overall survival (B) according to randomization arm. O: observed number of events; N: number of patients randomized; %: 8-year event-free or overall survival estimation according to the Kaplan-Meier technique, followed by the standard error (SE); (A) Treatment comparison adjusted for sex in a Cox model stratified by EORTC and NCI risk groups: HR, 0.94 (95% CI 0.76–1.16); P=0.57.

Figure 3.

Forest plots for event-free survival according to randomization arm. *NCI risk groups are described in Table 2. DEXA: dexamethasone; PRED: prednisolone; WBC: white blood cells; VLR: very low risk; AR: average risk; VHR: very high risk.