ASPG and acute lymphoblastic leukemia: Although it is not known how long circulating asparagine levels must be depleted for programmed cell death mechanisms to be activated in leukemic blasts, there is strong clinical evidence that prolonged exposure to asparaginase is associated with superior outcomes.93,94 The DFCI ALL Consortium Protocol 91-01 evaluated outcomes in 352 pediatric patients (aged 0–18 years) treated on an intensive 30 weeks of high-dose asparaginase during intensification.93 The investigators found an increased 5-year EFS in patients who were able to receive >25 weeks of asparaginase therapy.