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
Mirko Kroll,
Kirsten Kaupat-Bleckmann,
Anja Mörickel,
Julia Altenl,
Denis M. Schewel,
Martin Stanullal,
Martin Zimmermann,
Martin Schrappe,
Gunnar Cario
Affiliations
Mirko Kroll
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
Kirsten Kaupat-Bleckmann
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
Anja Mörickel
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
Julia Altenl
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
Denis M. Schewel
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
Martin Stanullal
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
Martin Zimmermann
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
Martin Schrappe
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
Gunnar Cario
Department of Pediatrics I, University Hospital Schleswig-Holstein, Kiel
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/m2 each) plus intrathecal MTX and 6-mercaptopurine (6-MP). From 2004 onwards, a dose of 0.5 g/m2 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/m2 MTX compared to NDS-patients (grade 3/4 toxicities 62 in 45 DS-patients vs. 516 in 1,089 NDS-patients, P
