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Drug monitoring of low‐dose PEG‐asparaginase (Oncaspar tm ) in children with relapsed acute lymphoblastic leukaemia
Author(s) -
Vieira Pinheiro J. P,
Müller H. J.,
Schwabe D.,
Gunkel M.,
Casimiro da Palma J.,
Henze G.,
Von Schütz V.,
Winkelhorst M.,
Würthwein G.,
Boos J.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02680.x
Subject(s) - asparaginase , medicine , peg ratio , polyethylene glycol , pharmacology , lymphoblastic leukemia , chemistry , leukemia , biochemistry , finance , economics
Use of asparaginase (ASNase) in the treatment of relapsed childhood acute lymphoblastic leukaemia (ALL) is associated with a high rate of hypersensitive reactions. ‘Silent’ inactivation may additionally reduce treatment intensity. Therefore, PEG‐ASNase (Oncaspar tm ), a polyethylene glycol conjugate of the native Escherichia coli ‐ASNase, was introduced into the Berlin‐Frankfurt‐Münster (BFM) 96 treatment protocol for relaped ALL under drug monitoring conditions. A single i.v. dose of 500 IU/m 2 PEG‐ASNase, substituted for the native ASNases, was administered to supply a plasma activity of 100 IU/l for 1 week. From November 1997 to March 2000, 35 patients from 23 BFM‐associated hospitals, with or without a previous allergic reaction to one or both native preparations, underwent monitoring. After 82 applications, a total of 270 samples were submitted to be tested for ASNase activity. The ASNase activity on the day of the administration and the following day ranged between < 20 and 693 IU/l, with a median of 413 IU/l (53 samples). The median on d 7 ± 1 was 199 IU/l (range <20–421 IU/l; 41 samples) and on d 14 ± 1, 105 IU/l (range <20–188 IU/l; 19 samples). An ASNase activity of > 100 IU/l was seen on d 7 in 36 activity time courses of 52 interpretable applications (69%). Intraindividual variability of activity time courses was low. However, a rapid decrease in ASNase activity after repeated applications was observed in 4 out of 20 children. Previously experienced allergic reactions to native ASNases did not influence PEG‐ASNase pharmacokinetics. PEG‐ASNase is a useful alternative to the native ASNases in children with relapsed ALL. Whenever possible, drug monitoring should be performed to identify patients with ‘silent’ inactivation.