Fig. 2

Schematic representation of risk-stratified treatment and randomised interventions in ICiCLe-ALL-14. Patients 1–18 years old with newly diagnosed acute lymphoblastic leukaemia (ALL) are categorised into four risk groups based on presentation features, disease genetics and treatment response: B cell precursor ALL (BCP-ALL) with standard (SR), intermediate (IR) and high risk (HR) disease (A) and T-ALL (B). All risk groups receive four consecutive blocks of intensive treatment (induction including a 7-day prednisolone prophase, consolidation, interim maintenance [IM] and delayed intensification [DI]), followed by 24 months of maintenance. Treatment intensity varies by risk group and is highest in HR and T-ALL patients. Treatment response is assessed by determining the prednisolone response (PR) at treatment day 8 and by serial bone marrow assessments (BMA, including microscopy studies and minimal residual disease estimation) at the end of the induction and consolidation treatment phases. Patients with persistent disease at the end of the consolidation phase are withdrawn from the study. Younger (< 10 years) SR and IR patients are randomised to receive the standard continuous schedule (R1 arm A) of prednisolone (4 weeks followed by taper) versus a shorter pulsed prednisolone schedule (R1 arm B, days 1–14, days 22–28) in induction. A second randomisation open to all risk groups randomises patients to receive either the standard 3 doses of doxorubicin (R2 arm A, DOX) or 1 dose of mitoxantrone (R2 arm B, Mitox) in DI. 6-MP, 6-mercaptopurine; ARA-C, cytarabine; CNS+, with central nervous system leukaemia; CTX, cyclophosphamide; Dauno, daunorubicin; DXM, dexamethasone; HD-MTX, high dose intravenous methotrexate; IT-MTX, intrathecal methotrexate; IV, intravenous; L-Asp, E. coli L-asparaginase; MRD, minimal residual disease; MTX, methotrexate; PRDL, prednisolone; VCR, vincristine; wk, week