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

Leuk Lymphoma. 2020 Jan;61(1):138-145. doi: 10.1080/10428194.2019.1658099. Epub 2019 Sep 3.

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 ≥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/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 ≥100 U/L activities over 14 days.

Keywords: Adult ALL; asparaginase activity; drug monitoring; pegylated E. coli asparaginase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents* / therapeutic use
  • Asparaginase / therapeutic use
  • Escherichia coli
  • Humans
  • Polyethylene Glycols / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • Asparaginase