Medline ® Abstract for Reference 39
of 'Overview of the treatment of acute lymphoblastic leukemia in children and adolescents'
Therapeutic drug monitoring of asparaginase in the ALL-BFM 2000 protocol between 2000 and 2007.
Schrey D, Borghorst S, Lanvers-Kaminsky C, Hempel G, Gerss J, Möricke A, Schrappe M, Boos J
Pediatr Blood Cancer. 2010 Jul;54(7):952-8.
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/m2 E. coli ASNase (n = 318), 1,000 U/m2 pegylated ASNase (n = 416) and 10,000 U/m2 Erwinia chrysanthemi ASNase (n = 29)).
RESULTS: First-line therapy with 5,000 U/m2 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/m2 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/m2 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/m2 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 dose reduction is reasonable and provide the basis for future treatment strategies employing ASNase.
Department of Paediatric Haematology and Oncology, University Hospital Muenster, Muenster, Germany.