Fig. 1

Study flow in ICiCLe-ALL-14/ Following determination of enrolment eligibility and after obtaining consent to participate, consecutive patients 1–18 years old with newly diagnosed acute lymphoblastic leukaemia (ALL) are recruited to the trial. The first randomisation in the induction phase (R1) is restricted to younger B cell precursor ALL patients (age < 10 years) with standard and intermediate risk disease (as determined by risk stratification at treatment day 8). R1 randomisation compares toxicity of continuous (R1A) versus a pulsed prednisolone schedule (R1B) in the induction treatment phase. A second randomisation (R2) later in treatment (delayed intensification) is open to all risk groups, including patients who have completed R1 randomisation. R2 randomisation compares survival outcome with 3 doses of doxorubicin (R2A) versus 1 dose of mitoxantrone (R2B) in the delayed intensification phase of treatment