Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia : A Danish population-based study
(2019) In Pediatric Blood & Cancer 2019.- Abstract
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
2
on the... (More)
(Less)
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
2
on the NOPHO2000 protocol. Moderately delayed MTX elimination was defined as 42-hour plasma MTX ≥ 4.0–9.9 μM, and severely delayed elimination was defined as 42-hour plasma MTX ≥ 10 μM. 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
2
(n = 140 patients) or 8 g/m
2
(n = 78 patients), 5.1% were severely (1.5%) or moderately (3.6%) delayed. The risk of having delayed elimination was highest in the first of eight infusions with MTX 5 g/m² (7.4% vs 0.0 to 4.1% for subsequent MTX infusions) (P < 0.02). A 25 μM increase or a 1.5-fold increase in plasma creatinine within 36 hours from start of the MTX infusion had a sensitivity of 92% (95% CI, 82%–97%) and a specificity of 85% (95% CI, 83%–87%) for predicting 42-hour MTX ≥4.0 μM. 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.
- author
- Schmidt, Diana ; Kristensen, Kim ; Schroeder, Henrik ; Wehner, Peder Skov ; Rosthøj, Steen ; Heldrup, Jesper LU ; Damsgaard, Linn ; Schmiegelow, Kjeld and Mikkelsen, Torben Stamm
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- acute leukemias, ALL, chemotherapy, methotrexate, support care cancer pharmacology
- in
- Pediatric Blood & Cancer
- volume
- 2019
- article number
- e27637
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:30835935
- scopus:85062522765
- ISSN
- 1545-5009
- DOI
- 10.1002/pbc.27637
- language
- English
- LU publication?
- no
- id
- 9eedf70b-1731-4974-aa1f-99226ce9076e
- date added to LUP
- 2019-03-19 08:46:49
- date last changed
- 2024-02-14 19:45:08
@article{9eedf70b-1731-4974-aa1f-99226ce9076e,
abstract = {{<p><br>
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 <br>
<sup>2</sup><br>
on the NOPHO2000 protocol. Moderately delayed MTX elimination was defined as 42-hour plasma MTX ≥ 4.0–9.9 μM, and severely delayed elimination was defined as 42-hour plasma MTX ≥ 10 μM. 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 <br>
<sup>2</sup><br>
(n = 140 patients) or 8 g/m <br>
<sup>2</sup><br>
(n = 78 patients), 5.1% were severely (1.5%) or moderately (3.6%) delayed. The risk of having delayed elimination was highest in the first of eight infusions with MTX 5 g/m² (7.4% vs 0.0 to 4.1% for subsequent MTX infusions) (P < 0.02). A 25 μM increase or a 1.5-fold increase in plasma creatinine within 36 hours from start of the MTX infusion had a sensitivity of 92% (95% CI, 82%–97%) and a specificity of 85% (95% CI, 83%–87%) for predicting 42-hour MTX ≥4.0 μM. 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. <br>
</p>}},
author = {{Schmidt, Diana and Kristensen, Kim and Schroeder, Henrik and Wehner, Peder Skov and Rosthøj, Steen and Heldrup, Jesper and Damsgaard, Linn and Schmiegelow, Kjeld and Mikkelsen, Torben Stamm}},
issn = {{1545-5009}},
keywords = {{acute leukemias; ALL; chemotherapy; methotrexate; support care cancer pharmacology}},
language = {{eng}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Pediatric Blood & Cancer}},
title = {{Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia : A Danish population-based study}},
url = {{http://dx.doi.org/10.1002/pbc.27637}},
doi = {{10.1002/pbc.27637}},
volume = {{2019}},
year = {{2019}},
}