University of Oulu

Niinimäki, R., Aarnivala, H., Banerjee, J. et al. Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort. Support Care Cancer 30, 127–133 (2022).

Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

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Author: Niinimäki, Riitta1,2; Aarnivala, Henri1,2; Banerjee, Joanna3;
Organizations: 1Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
2PEDEGO Research Unit, University of Oulu, Oulu, Finland
3Children and Adolescents Hospital, Helsinki University Hospital, Helsinki, Finland
4Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland
5Department of Women’s and Children’s Health, Uppsala University Hospital, Uppsala, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
Persistent link:
Language: English
Published: Springer Nature, 2022
Publish Date: 2022-03-08


Purpose: Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity.

Methods: We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m² HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m² doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected.

Results: Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given.

Conclusion: A pharmacokinetically guided FA rescue of one or two 15 mg/m² doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

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Series: Supportive care in cancer
ISSN: 0941-4355
ISSN-E: 1433-7339
ISSN-L: 0941-4355
Volume: 30
Issue: 1
Pages: 127 - 133
DOI: 10.1007/s00520-021-06395-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Open access funding provided by University of Oulu including Oulu University Hospital. This study was supported by the Alma and K. A: Snellman Foundation, Oulu, Finland.
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