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Medientyp:
E-Artikel
Titel:
Pegylated asparaginase (OncasparTM) in children with ALL: drug monitoring in reinduction according to the ALL/NHL‐BFM 95 protocols
Beteiligte:
Müller, Hans‐Joachim;
Löning, Lutz;
Horn, Alexander;
Schwabe, Dirk;
Gunkel, Martin;
Schrappe, Martin;
Von Schütz, Volker;
Henze, Günter;
Casimiro da Palma, João;
Ritter, Jörg;
Pinheiro, João Paulo Vieira;
Winkelhorst, Monika;
Boos, Joachim
Erschienen:
Wiley, 2000
Erschienen in:British Journal of Haematology
Sprache:
Englisch
DOI:
10.1046/j.1365-2141.2000.02187.x
ISSN:
0007-1048;
1365-2141
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>Hypersensitivity reactions are relevant adverse effects of asparaginase therapy. Therefore, children treated with native <jats:italic>Escherichia coli</jats:italic> asparaginase in induction therapy of acute lymphoblastic leukaemia (ALL) or non‐Hodgkin's lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug monitoring. Seventy children, including four patients with allergic reactions during induction, were given one dose of Oncaspar<jats:sup>TM</jats:sup> 1000 U/m<jats:sup>2</jats:sup> intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL‐Berlin–Frankfurt–Münster (BFM) 95 trials], four doses of 10 000 U/m<jats:sup>2</jats:sup><jats:italic>E. coli</jats:italic> asparaginase deplete asparagine for about 2–3 weeks, therefore activities of ≥ 100 U/l up to day 14 and ≥ 50 U/l up to day 21 were targeted. In 66 patients without an allergic reaction during induction, the mean activity was 606 ± 313 U/l, 232 ± 211 U/l and 44 ± 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was ≥ 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native enzymes but, in contrast to about 30% of hypersensitivity reactions with conventional reinduction therapy, no allergic reaction was seen. Substituting 4 × 10 000 U/m<jats:sup>2</jats:sup> asparaginase medac for one dose of 1000 U/m<jats:sup>2</jats:sup> Oncaspar<jats:sup>TM</jats:sup> was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two‐thirds of patients.</jats:p>