Effect of dexamethasone (DEX) dose modification on osteonecrosis (ON) risk associated with intensified therapies for standard risk acute lymphoblastic leukemia (SR-ALL): A report from the Children’s Oncology Group (COG) study AALL0331

10002 Background: ON is a known toxicity of childhood ALL therapy, particularly in patients (pts) >9 years (y). Intensified use of DEX, methotrexate (MTX), and asparaginase (ASNase) may increase the risk of developing ON among B-precursor NCI SR-ALL pts despite their younger age. Methods: Newly diagnosed SR-ALL pts 1-9y enrolled on AALL0331 between 4/05 and 5/10 were prospectively monitored for symptomatic ON within three treatment cohorts risk-stratified by clinical, cytogenetic, and early response criteria. ON sites were confirmed by imaging. SR-Low (SRL) pts were randomized to standard therapy +/- 4 additional doses of PEG-ASNase. SR-Average (SRA) pts were randomized (2x2) to standard therapy +/- an intensive consolidation (IC) +/- an augmented interim maintenance/delayed intensification (AIM/ADI). SR-High (SRH) pts all received IC and two AIM/ADI phases. After 6/08, alternate week DEX (AWD, days 1-7/15-21) replaced continuous DEX (days 1-21) during DI, and escalating-dose MTX replaced oral MTX during IM. All pts received DEX days 1-28 during induction and 5-day pulses every 4 weeks during maintenance. Results: Overall ON cumulative incidence (CI) at 5y was 2.7% (133/5261), correlating with sex (F 3.7%, M 1.9%, p