TY - JOUR
T1 - The effect of asparaginase therapy on methotrexate toxicity and efficacy in children with acute lymphoblastic leukemia
AU - Kloos, Robin Q. H.
AU - Pieters, Rob
AU - van den Bos, Cor
AU - van Eijkelenburg, Natasha K. A.
AU - de Jonge, Robert
AU - van der Sluis, Inge M.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066817733&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31120351
U2 - https://doi.org/10.1080/10428194.2019.1613537
DO - https://doi.org/10.1080/10428194.2019.1613537
M3 - Article
C2 - 31120351
SN - 1042-8194
VL - 60
SP - 3002
EP - 3010
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 12
ER -