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.