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

Lanvers-Kaminsky C, Niemann A, Eveslage M, Beck J, Köhnke T, Martin S, Wit M, Spriewald B, Hauspurg H, Hoelzer D, Boos J, Gökbuget N

Abstract

The GMALL07/2003 protocol introduced pegylated E. coli asparaginase (PEG-ASNase) frontline for adults with acute lymphoblastic leukemia (ALL). PEG-ASNase (500 U/m2, 1000 U/m2, or 2000 U/m2) 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 $\geq$100 U/L depended on protocol and dose. Overall PEG-ASNase activities were higher during consolidation compared to induction. To target PEG-ASNase activities $\geq$100 U/L for 14 day with a single dose in induction, 2000 U/m2 was more preferable than 1000 U/m2 or 500 U/m2. During consolidation with two administrations every other week, 1000 U/m2 and 2000 U/m2 were similarly effective in sustaining PEG-ASNase $\geq$100 U/L activities over 14 days.