The association between antimetabolite dose intensity (DI) and adverse events among children receiving maintenance therapy for acute lymphoblastic leukemia (ALL) remains unclear, especially in context of antimetabolite adherence. Using COG-AALL03N1 data, we examined the association between high DI during the first four study months and (i) treatment-related toxicities during the subsequent two study months; and (ii) relapse risk. Patients were classified into a high DI phenotype …