Therapeutic Drug Monitoring of Asparaginase in the ALL-BFM 2000 Protocol Between 2000 and 2007

Background. On a voluntary basis therapeutic drug monitoring (TDM) was implemented in the ALL-BFM 2000 protocol for the three currently used asparaginase (ASNase) preparations (first line: native Escherichia coli ASNase; second line: pegylated ASNase and third line: Erwinia chrysanthemi ASNase). Procedure. Between 2000 and 2007, 2,074 ASNase samples from 763 patients out of 114 hospitals were evaluated (5,000 U/m(2) E. coli ASNase (n = 318), 1,000 U/m(2) pegylated ASNase (n = 416) and 10,000 U/m(2) Erwinia chrysanthemi ASNase (n = 29)). Results. First-line therapy with 5,000 U/m(2) E. coli ASNase resulted in an ASNase activity of <100 U/L in 10% of all samples from day +3 after administration. Second-line treatment with 1,000 U/m(2) PEG ASNase led to activity values below 100 U/L in approximately 30% of all samples taken +7 days. Relating ASNase activity to route of administration, 10,000 U/m(2) Erwinia ASNase IM compared to IV as third-line treatment, led to a higher median activity (IM: median 151.5 U/L, range (0-750 U/L); IV: median 115 U/L, range (0-884 U/L), P=0.3) and fewer samples below 100 U/L (IM: 15% vs. IV: 45%) at day +2. Conclusion. The reduced dose of 5,000 U/m(2) E. coli ASNase for induction treatment succeeded to achieve an activity level above 100 U/L in more than 90% of all samples. They confirm that close reduction is reasonable and provide the basis for future treatment strategies employing ASNase. Pediatr Blood Cancer 2010;54:952-958. (C) 2010 Wiley-Liss, Inc.