Background: COG AALL0331 administered PEG IM in induction (IND) and Delayed intensification (DI) whereas AALL0932 administers the same dose IV. We compared grade 3/4 toxicities resulting from the single doses of PEG given in the IND and DI phases on the standard arms of AALL0331 and AALL0932 that gave only 2 doses of PEG (excluded arms with additional PEG). Methods: AALL0331 and AALL0932 shared a common 3 drug IND: dexamethasone (DEX) 6 mg/m²/day X 28 days, vincristine (VCR) 1.5 mg/m²/dose on days 1, 8, 15, 22, IT methotrexate (age adjusted dosing) on days 8, 29, and PEG 2500 units/m²/dose IM on day 4, 5, or 6 (AALL0331) or IV on day 4 (AALL0932). DI (Days 1-28) for both protocols consisted of: DEX 10 mg/m²/day (days1-7, 15-22), VCR 1.5 mg/m²/dose and Doxorubicin 25 mg/m²/dose IV (days 1, 8, 15), PEG 2500 units/m²on day 4 (AALL03131 IM; AALL0932 IV). Toxicity was graded using CTCAE v4.0, however, AALL0331 collected data using CTCAE v3.0, which was subsequently mapped to v4.0. Results: During IND, the rates of anaphylaxis/allergic reaction were similar between IM and IV PEG (0.2% vs. 0.3%, p = 0.842). The rate of anaphylaxis/allergic reaction in DI was 0.5% (IM) vs 1.8% (IV) (p = 0.007). The rates of pancreatitis, elevated lipase and amylase, and hyperglycemia were similar between IM and IV PEG in both IND and DI. Conclusions: The rates of AEs with PEG administration (IV or IM) are low but more grade 3/4 anaphylaxis/allergic reactions were reported with IV PEG compared to IM PEG during DI. This may be due to more stringent reporting on 0932 or the challenges of determining infusion reactions vs. allergic reactions when PEG is administered IV. Clinical trial information: NCT00103285