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Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia

SIMPLE SUMMARY: In this study, we investigated standardized post-chemotherapy magnetic resonance (MR) scans for leukoencephalopathy and patient- and treatment-related risk factors in childhood leukemia patients. As prevalence numbers are limited, our study provides the required estimations for this...

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Autores principales: Rijmenams, Ilona, Moechars, Daan, Uyttebroeck, Anne, Radwan, Ahmed, Blommaert, Jeroen, Deprez, Sabine, Sunaert, Stefan, Segers, Heidi, Gillebert, Céline R., Lemiere, Jurgen, Sleurs, Charlotte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073318/
https://www.ncbi.nlm.nih.gov/pubmed/33923795
http://dx.doi.org/10.3390/cancers13081939
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author Rijmenams, Ilona
Moechars, Daan
Uyttebroeck, Anne
Radwan, Ahmed
Blommaert, Jeroen
Deprez, Sabine
Sunaert, Stefan
Segers, Heidi
Gillebert, Céline R.
Lemiere, Jurgen
Sleurs, Charlotte
author_facet Rijmenams, Ilona
Moechars, Daan
Uyttebroeck, Anne
Radwan, Ahmed
Blommaert, Jeroen
Deprez, Sabine
Sunaert, Stefan
Segers, Heidi
Gillebert, Céline R.
Lemiere, Jurgen
Sleurs, Charlotte
author_sort Rijmenams, Ilona
collection PubMed
description SIMPLE SUMMARY: In this study, we investigated standardized post-chemotherapy magnetic resonance (MR) scans for leukoencephalopathy and patient- and treatment-related risk factors in childhood leukemia patients. As prevalence numbers are limited, our study provides the required estimations for this population. Furthermore, we demonstrate that younger patients might be more at-risk for development of leukoencephalopathy (LE), and that a higher intravenous methotrexate (IV-MTX) dose has a cumulative toxic effect, while the number of intrathecal administrations was not significantly associated with the extent of LE. This can suggest we should modify chemotherapeutic treatment regimens by decreasing the number of IV-MTX applications, with special attention for younger patients. ABSTRACT: Methotrexate (MTX) is associated with leukoencephalopathy (LE) in children treated for lymphoblastic leukemia/lymphoma (ALL/LBL). However, large-scale studies with systematic MR acquisition and quantitative volumetric lesion information remain limited. Hence, the prevalence of lesion burdens and the potential risk factors of LE in this population are still inconclusive. FLAIR-MRI scans were acquired at the end of treatment in children who were treated for ALL/LBL, which were quantitatively analyzed for LE. Voxels were assigned to the lesion segmentation if indicated by two raters. Logistic and linear regression models were used to test whether lesion presence and size were predicted by risk factors such as age at diagnosis, gender, intrathecal (IT-) or intravenous (IV-)MTX dose, CNS invasion, and acute neurological events. Patients with a pre-existing neurological condition or low-quality MR scan were excluded from the analyses. Of the 129 patients, ten (8%) suffered from CNS invasion. Chemotherapy-associated neurological events were observed in 13 patients (10%) during therapy, and 68 patients (53%) showed LE post-treatment. LE was more frequent in cases of lower age and higher cumulative IV-MTX doses, while the extent of LE and neurological symptoms were associated only with IV-MTX doses. Neurological events were not significantly associated with LE, even though symptomatic patients demonstrated a higher ratio of LE (n = 9/13) than asymptomatic patients (n = 59/116). This study suggests leukoencephalopathy frequently occurs in both symptomatic and asymptomatic leukemia patients. Younger children and patients treated with higher cumulative IV-MTX doses might need more regular screening for early detection and follow-up of associated sequelae.
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spelling pubmed-80733182021-04-27 Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia Rijmenams, Ilona Moechars, Daan Uyttebroeck, Anne Radwan, Ahmed Blommaert, Jeroen Deprez, Sabine Sunaert, Stefan Segers, Heidi Gillebert, Céline R. Lemiere, Jurgen Sleurs, Charlotte Cancers (Basel) Article SIMPLE SUMMARY: In this study, we investigated standardized post-chemotherapy magnetic resonance (MR) scans for leukoencephalopathy and patient- and treatment-related risk factors in childhood leukemia patients. As prevalence numbers are limited, our study provides the required estimations for this population. Furthermore, we demonstrate that younger patients might be more at-risk for development of leukoencephalopathy (LE), and that a higher intravenous methotrexate (IV-MTX) dose has a cumulative toxic effect, while the number of intrathecal administrations was not significantly associated with the extent of LE. This can suggest we should modify chemotherapeutic treatment regimens by decreasing the number of IV-MTX applications, with special attention for younger patients. ABSTRACT: Methotrexate (MTX) is associated with leukoencephalopathy (LE) in children treated for lymphoblastic leukemia/lymphoma (ALL/LBL). However, large-scale studies with systematic MR acquisition and quantitative volumetric lesion information remain limited. Hence, the prevalence of lesion burdens and the potential risk factors of LE in this population are still inconclusive. FLAIR-MRI scans were acquired at the end of treatment in children who were treated for ALL/LBL, which were quantitatively analyzed for LE. Voxels were assigned to the lesion segmentation if indicated by two raters. Logistic and linear regression models were used to test whether lesion presence and size were predicted by risk factors such as age at diagnosis, gender, intrathecal (IT-) or intravenous (IV-)MTX dose, CNS invasion, and acute neurological events. Patients with a pre-existing neurological condition or low-quality MR scan were excluded from the analyses. Of the 129 patients, ten (8%) suffered from CNS invasion. Chemotherapy-associated neurological events were observed in 13 patients (10%) during therapy, and 68 patients (53%) showed LE post-treatment. LE was more frequent in cases of lower age and higher cumulative IV-MTX doses, while the extent of LE and neurological symptoms were associated only with IV-MTX doses. Neurological events were not significantly associated with LE, even though symptomatic patients demonstrated a higher ratio of LE (n = 9/13) than asymptomatic patients (n = 59/116). This study suggests leukoencephalopathy frequently occurs in both symptomatic and asymptomatic leukemia patients. Younger children and patients treated with higher cumulative IV-MTX doses might need more regular screening for early detection and follow-up of associated sequelae. MDPI 2021-04-16 /pmc/articles/PMC8073318/ /pubmed/33923795 http://dx.doi.org/10.3390/cancers13081939 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rijmenams, Ilona
Moechars, Daan
Uyttebroeck, Anne
Radwan, Ahmed
Blommaert, Jeroen
Deprez, Sabine
Sunaert, Stefan
Segers, Heidi
Gillebert, Céline R.
Lemiere, Jurgen
Sleurs, Charlotte
Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia
title Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia
title_full Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia
title_fullStr Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia
title_full_unstemmed Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia
title_short Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia
title_sort age- and intravenous methotrexate-associated leukoencephalopathy and its neurological impact in pediatric patients with lymphoblastic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073318/
https://www.ncbi.nlm.nih.gov/pubmed/33923795
http://dx.doi.org/10.3390/cancers13081939
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