Treatment
Details of treatment for HR-I patients are summarized in figure 1. There were no major modifications in the treatment backbone compared to the preceding trial CoALL07-03 except a randomized comparison between high dose cytarabine and clofarabine both combined with asparaginase as the first consolidation block and the use of pegylated asparaginase (PEG-ASP) from the first dose onwards in CoALL08-09 whereas in the CoALL-07-03 native coli-asparaginase was scheduled for the first two asparaginase doses followed by PEG-ASP for the subsequent doses . For patients stratified into the HR-I treatment arm the AEP block was added to the treatment protocol at the end of the consolidation phase. Besides, in the central nervous system (CNS) phase an additional dose of daunorubicin, vincristine and PEG-ASP along with a seven-day course of dexamethasone was scheduled.
Patients that failed to achieve remission EOI were assigned to an MRD-guided treatment according to protocol which included (for details see supplemental table S1) . In case of MRD negativity after the first CoALL-HR1 block, patients resumed on-protocol therapy (HR-I arm) after the second CoALL-HR1 block. All patients with IF and MRD positivity after the first CoALL-HR1 block were eligible for an allogenic HSCT and received an AEP block after the second CoALL-HR1 block.