The effect of asparaginase therapy on methotrexate toxicity and efficacy in children with acute lymphoblastic leukemia

Robin Q. H. Kloos, Rob Pieters, Cor van den Bos, Natasha K. A. van Eijkelenburg, Robert de Jonge, Inge M. van der Sluis

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Asparaginase and methotrexate (MTX), both essential for pediatric acute lymphoblastic leukemia therapy, are often used concomitantly. Depending on the sequence, in vitro, asparaginase inhibits MTX-polyglutamate (MTXPG) formation, and side effects overlap. MTX toxicity and efficacy, reflected by intracellular erythrocyte MTXPG’s, were compared between children treated with and without asparaginase during high dose MTX (HD-MTX) courses of the DCOG ALL-11 protocol (NL50250.078.14). Seventy-three patients, of whom 23 received asparaginase during the HD-MTX courses, were included. Grade 3–4 leukopenia and neutropenia occurred more often (59% and 86% vs. 30% and 62%). The number of infections, grade 3–4 hepatotoxicity, nephrotoxicity, and neurotoxicity did not differ. Patients with asparaginase had lower MTXPG levels, although to a lesser extent than in vitro studies. Although patients with asparaginase during HD-MTX courses showed more myelosuppression, this had no (serious) clinical consequences. Regarding the MTX efficacy, the schedule-related antagonism seen in in vitro seems less important in vivo.
Original languageEnglish
Pages (from-to)3002-3010
Number of pages9
JournalLeukemia and Lymphoma
Issue number12
Publication statusPublished - 15 Oct 2019

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