Risk assignment algorithms. Each of the algorithms shows the criteria for placement of patients in (A) standard-risk, (B) high-risk, and (C) very-high-risk assignment. Very-high-risk assignment occurs independently of initial NCI risk assignment (standard or high risk). Patients who have received less than 48 hours of oral or intravenous steroids during the week immediately prior to diagnosis are eligible for classification if the results of a complete blood count (CBC), obtained prior to the initiation of steroid therapy (less than 72 hours prior to steroids), are available and the necessary FISH, cytogenetic, and molecular data are interpretable. The “presteroid” CBC and age of the patient are used to determine NCI-Rome risk classification (standard risk versus high risk [SR versus HR]). If patients have received more than 48 hours of oral or intravenous steroids (and a presteroid CBC is available to assign NCI risk group), they are treated as an SER and nonrandomly assigned to the augmented regimen. In the absence of a presteroid CBC, patients who have received less than 48 hours of steroids are assigned to the HR protocol. These patients are eligible for randomization on the HR protocol. As expected, patients with a slow early response will be assigned to the full augmented BFM treatment arm. In the absence of a presteroid CBC, patients who have received more than 48 hours of steroids are treated as an SER on the HR study and assigned to the full augmented arm. Inhalational steroids are not considered as pretreatment. Both SR and HR patients with identified MLL translocations, CNS-3, or testicular disease, receive augmented SR therapy.