The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: A systematic review

J. N. van der Beek, N. Oosterom, R. Pieters, R. de Jonge, M. M. van den Heuvel-Eibrink, S. G. Heil

Research output: Contribution to journalReview articleAcademicpeer-review

21 Citations (Scopus)


Introduction: This study aimed to determine the efficacy of different Leucovorin regimens to reduce oral mucositis in children with acute lymphoblastic leukemia after high-dose Methotrexate (HD-MTX). Methods: Twelve articles were included in a systematic literature review. Articles were categorized into low/medium/high risk of bias. Results: As no randomized controlled trial assessing the effect of Leucovorin has been performed, the efficacy of Leucovorin to reduce oral mucositis remains unknown. Leucovorin was initiated at 24, 36 or 42 h after HD-MTX at a dose of 15 or 30 mg/m2. No meta-analysis could be performed as treatment regimens differed. When comparing studies with similar HD-MTX doses, we observed lower oral mucositis rates in regimens with higher cumulative doses of Leucovorin and early initiation of Leucovorin after MTX. Conclusion: Even though future studies are necessary, higher cumulative Leucovorin doses and early initiation of Leucovorin after start of MTX seem to reduce oral mucositis.
Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalCritical Reviews in Oncology/Hematology
Publication statusPublished - Oct 2019


  • Acute lymphoblastic leukemia
  • Leucovorin
  • Methotrexate
  • Oral mucositis

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