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

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents. Children with Down syndrome (trisomy 21) have a 30-times higher risk of acquiring ALL and pose up to 5% of all pediatric ALL patients. Moreover, many Down syndrome-ALL patients (DS-ALL) suffer from severe toxicity during chemotherapy, especially after application of high dose methotrexate (HD-MTX). Severe toxicities often result in MTX dose reduction, which may be associated with a higher probability of relapse. Systematic and comprehensive toxicity data in a large cohort of uniformly treated DS-ALL patients are lacking.In order to extend our knowledge on MTX-associated toxicities in DS-ALL, we analyzed clinical data from 103 DS-ALL and 1109 Non-DS-ALL (NDS-ALL) patients diagnosed between 1995 and 2016 treated according to German ALL-BFM protocols (ALL-BFM 1995, ALL-BFM 2000 and AIEOP-BFM ALL 2009). We only included patients for whom both therapy and toxicity data were available. We focused on toxicity after HD-MTX administration during the 8-week HD-MTX consolidation in which patients receive 4 courses of intravenous HD-MTX (5 g/m2 each) plus intrathecal MTX in addition to 6-mercaptopurine (25 mg/m2/d). As of 2004, it was recommended for DS-ALL to administer the first MTX course with a reduced dose of 0.5 g/m2 and subsequently increase the dose if no severe toxicity occurs. Toxicity grading was performed according to CTC 2.0.From the 103 DS-ALL patients four switched to high risk tr...
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster I Source Type: research