Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia: A Danish population-based study.


Journal

Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624

Informations de publication

Date de publication:
06 2019
Historique:
received: 02 10 2018
revised: 04 01 2019
accepted: 07 01 2019
pubmed: 6 3 2019
medline: 19 12 2019
entrez: 6 3 2019
Statut: ppublish

Résumé

Severely delayed elimination of methotrexate (MTX) is difficult to predict in patients treated with high-dose MTX (HD-MTX), but it may cause life-threatening toxicity. It has not been defined how an increase in plasma creatinine can be best used as a predictor for severely delayed MTX elimination, thus providing a guide for therapeutic interventions to minimize renal toxicity. Pharmacokinetic data were retrospectively collected on 218 Danish children with acute lymphoblastic leukemia treated with HD-MTX 5 or 8 g/m Median 42-hour plasma MTX was 0.61 μM (interquartile range, 0.4-1.06 μM). Of 1295 MTX infusions with 5 g/m A 25 μM increase or a 1.5-fold in plasma creatinine within 36 hours after start of an HD-MTX infusion can predict delayed MTX elimination, thus allowing intensification of hydration and alkalization to avoid further renal toxicity and promote the elimination of MTX.

Sections du résumé

BACKGROUND
Severely delayed elimination of methotrexate (MTX) is difficult to predict in patients treated with high-dose MTX (HD-MTX), but it may cause life-threatening toxicity. It has not been defined how an increase in plasma creatinine can be best used as a predictor for severely delayed MTX elimination, thus providing a guide for therapeutic interventions to minimize renal toxicity.
METHODS
Pharmacokinetic data were retrospectively collected on 218 Danish children with acute lymphoblastic leukemia treated with HD-MTX 5 or 8 g/m
RESULTS
Median 42-hour plasma MTX was 0.61 μM (interquartile range, 0.4-1.06 μM). Of 1295 MTX infusions with 5 g/m
CONCLUSIONS
A 25 μM increase or a 1.5-fold in plasma creatinine within 36 hours after start of an HD-MTX infusion can predict delayed MTX elimination, thus allowing intensification of hydration and alkalization to avoid further renal toxicity and promote the elimination of MTX.

Identifiants

pubmed: 30835935
doi: 10.1002/pbc.27637
doi:

Substances chimiques

Creatinine AYI8EX34EU
Mercaptopurine E7WED276I5
Methotrexate YL5FZ2Y5U1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e27637

Informations de copyright

© 2019 Wiley Periodicals, Inc.

Auteurs

Diana Schmidt (D)

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.

Kim Kristensen (K)

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
Development DMPK, PKPD, Novo Nordisk A/S, Maaløv, Denmark.

Henrik Schroeder (H)

Department of Pediatric Oncology, Aarhus University Hospital, Aarhus, Denmark.

Peder Skov Wehner (PS)

Department of Pediatric Hematology and Oncology, H.C. Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

Steen Rosthøj (S)

Department of Pediatric Oncology, Aalborg University Hospital, Aalborg, Denmark.

Jesper Heldrup (J)

Department of Pediatric Oncology, Lund University Hospital, Lund, Sweden.

Linn Damsgaard (L)

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.

Kjeld Schmiegelow (K)

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Torben Stamm Mikkelsen (TS)

Department of Pediatric Oncology, Aarhus University Hospital, Aarhus, Denmark.

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