NDLI: Late effects of high-dose methotrexate treatment in childhood cancer survivors

Content Provider	Springer Nature : BioMed Central
Author	Daetwyler, Eveline Bargetzi, Mario Otth, Maria Scheinemann, Katrin
Abstract	Background High-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m2 body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking. Method We conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262). Results We included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision. Conclusions CCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-021-09145-0.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-021-09145-0
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-03-14
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Paediatric cancer Cancer survivor High-dose methotrexate Late effects Follow-up care Systematic review Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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