Methotrexate-associated toxicity in children with Down syndrome and acute lymphoblastic leukemia during consolidation therapy with high dose methotrexate according to ALL-BFM treatment regimen

Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) often suffer from severe toxicities during treatment, especially with high-dose methotrexate (HD-MTX). Systematic data on methotrexate (MTX) toxicity in these patients are rare. We analyzed seven MTX-associated toxicities during...

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Bibliographic Details
Published in:Haematologica (Roma) 2020-04, Vol.105 (4), p.1013-1020
Main Authors: Kroll, Mirko, Kaupat-Bleckmann, Kirsten, Mörickel, Anja, Altenl, Julia, Schewel, Denis M, Stanullal, Martin, Zimmermann, Martin, Schrappe, Martin, Cario, Gunnar
Format: Article
Language:English
Subjects:
Child
Consolidation Chemotherapy
Down Syndrome
Humans
Mercaptopurine - adverse effects
Methotrexate - adverse effects
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
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Summary:Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) often suffer from severe toxicities during treatment, especially with high-dose methotrexate (HD-MTX). Systematic data on methotrexate (MTX) toxicity in these patients are rare. We analyzed seven MTX-associated toxicities during consolidation therapy in 103 DS- and 1,109 non-DS-patients (NDS) with ALL (NDS-ALL) enrolled in ALL-Berlin-Frankfurt-Münster (ALL-BFM) trials between 1995-2016 and 1995-2007, respectively. Patients received four courses MTX (5 g/m each) plus intrathecal MTX and 6-mercaptopurine (6-MP). From 2004 onwards, a dose of 0.5 g/m in the first MTX course has been recommended for DS-patients. DS-patients showed higher rates of grade 3/4 toxicities after the first course with 5 g/m MTX compared to NDS-patients (grade 3/4 toxicities 62 in 45 DS-patients 516 in 1,089 NDS-patients,
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2019.224774