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

Research output: Contribution to journalArticle

Standard

Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia : A Danish population-based study. / Schmidt, Diana; Kristensen, Kim; Schroeder, Henrik; Wehner, Peder Skov; Rosthøj, Steen; Heldrup, Jesper; Damsgaard, Linn; Schmiegelow, Kjeld; Mikkelsen, Torben Stamm.

In: Pediatric Blood and Cancer, Vol. 2019, e27637, 2019.

Research output: Contribution to journalArticle

Harvard

Schmidt, D, Kristensen, K, Schroeder, H, Wehner, PS, Rosthøj, S, Heldrup, J, Damsgaard, L, Schmiegelow, K & Mikkelsen, TS 2019, 'Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia: A Danish population-based study', Pediatric Blood and Cancer, vol. 2019, e27637. https://doi.org/10.1002/pbc.27637

APA

CBE

MLA

Vancouver

Author

Schmidt, Diana ; Kristensen, Kim ; Schroeder, Henrik ; Wehner, Peder Skov ; Rosthøj, Steen ; Heldrup, Jesper ; Damsgaard, Linn ; Schmiegelow, Kjeld ; Mikkelsen, Torben Stamm. / Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia : A Danish population-based study. In: Pediatric Blood and Cancer. 2019 ; Vol. 2019.

RIS

TY - JOUR

T1 - Plasma creatinine as predictor of delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia

T2 - A Danish population-based study

AU - Schmidt, Diana

AU - Kristensen, Kim

AU - Schroeder, Henrik

AU - Wehner, Peder Skov

AU - Rosthøj, Steen

AU - Heldrup, Jesper

AU - Damsgaard, Linn

AU - Schmiegelow, Kjeld

AU - Mikkelsen, Torben Stamm

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - acute leukemias

KW - ALL

KW - chemotherapy

KW - methotrexate

KW - support care cancer pharmacology

U2 - 10.1002/pbc.27637

DO - 10.1002/pbc.27637

M3 - Article

VL - 2019

JO - Pediatric Blood & Cancer

JF - Pediatric Blood & Cancer

SN - 1545-5017

M1 - e27637

ER -