Asparaginase activities during intensified treatment with pegylated asparaginase in adults with newly-diagnosed acute lymphoblastic leukemia.

The GMALL07/2003 protocol introduced pegylated asparaginase (PEG-ASNase) frontline for adults with acute lymphoblastic leukemia (ALL). PEG-ASNase (500 U/m, 1000 U/m, or 2000 U/m) was given once in induction and as part of three HD-MTX/PEG-ASNase cycles with two PEG-ASNase doses every other week in consolidation. PEG-ASNase activities were monitored in 1363 serum samples from 304 ALL patients. The overall rate of silent inactivation was low (5%) and did not differ between induction and consolidation. The successful targeting of PEG-ASNase activities ≥100 U/L depended on protocol and dose. Overall PEG-ASNase activities were higher during consolidation compared to induction. To target PEG-ASNase activities ≥100 U/L for 14 day with a single dose in induction, 2000 U/m was more preferable than 1000 U/m or 500 U/m. During consolidation with two administrations every other week, 1000 U/m and 2000 U/m were similarly effective in sustaining PEG-ASNase ≥100 U/L activities over 14 days.