Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients

Anthony M. Christensen, Jennifer L. Pauley, Alejandro R. Molinelli, John C. Panetta, Deborah A. Ward, Clinton F. Stewart, James M. Hoffman, Scott Howard, Ching Hon Pui, Alberto S. Pappo, Mary V. Relling, Kristine R. Crews

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32 Citations (Scopus)

Abstract

Background: High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. The authors retrospectively reviewed glucarpidase use in pediatric cancer patients at their institution and evaluated whether subsequent resumption of HDMTX was tolerated. Methods: Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed. Results: Of 1141 patients who received 4909 courses of HDMTX, 20 patients (1.8% of patients, 0.4% of courses) received 22 doses of glucarpidase. The median glucarpidase dose was 51.6 U/kg (range, 13-65.6 U/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 μM (range, 1.3-590.6 μM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244-763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66-268 hours) for the next HDMTX course, and 72 hours (range, 42-116 hours) for subsequent courses. The median peak serum creatinine level during these HDMTX courses was 2.2 mg/dL (range, 0.8-9.6 mg/dL), 0.8 mg/dL (range, 0.4-1.6 mg/dL), and 0.6 mg/dL (range, 0.4-0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients, and no patient died as a result of methotrexate toxicity. Conclusions: The current results indicated that it is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury.

Original languageEnglish (US)
Pages (from-to)4321-4330
Number of pages10
JournalCancer
Volume118
Issue number17
DOIs
StatePublished - Sep 1 2012

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Acute Kidney Injury
Methotrexate
Pediatrics
Creatinine
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Christensen, A. M., Pauley, J. L., Molinelli, A. R., Panetta, J. C., Ward, D. A., Stewart, C. F., ... Crews, K. R. (2012). Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients. Cancer, 118(17), 4321-4330. https://doi.org/10.1002/cncr.27378

Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients. / Christensen, Anthony M.; Pauley, Jennifer L.; Molinelli, Alejandro R.; Panetta, John C.; Ward, Deborah A.; Stewart, Clinton F.; Hoffman, James M.; Howard, Scott; Pui, Ching Hon; Pappo, Alberto S.; Relling, Mary V.; Crews, Kristine R.

In: Cancer, Vol. 118, No. 17, 01.09.2012, p. 4321-4330.

Research output: Contribution to journalArticle

Christensen, AM, Pauley, JL, Molinelli, AR, Panetta, JC, Ward, DA, Stewart, CF, Hoffman, JM, Howard, S, Pui, CH, Pappo, AS, Relling, MV & Crews, KR 2012, 'Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients', Cancer, vol. 118, no. 17, pp. 4321-4330. https://doi.org/10.1002/cncr.27378
Christensen AM, Pauley JL, Molinelli AR, Panetta JC, Ward DA, Stewart CF et al. Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients. Cancer. 2012 Sep 1;118(17):4321-4330. https://doi.org/10.1002/cncr.27378
Christensen, Anthony M. ; Pauley, Jennifer L. ; Molinelli, Alejandro R. ; Panetta, John C. ; Ward, Deborah A. ; Stewart, Clinton F. ; Hoffman, James M. ; Howard, Scott ; Pui, Ching Hon ; Pappo, Alberto S. ; Relling, Mary V. ; Crews, Kristine R. / Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients. In: Cancer. 2012 ; Vol. 118, No. 17. pp. 4321-4330.
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abstract = "Background: High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. The authors retrospectively reviewed glucarpidase use in pediatric cancer patients at their institution and evaluated whether subsequent resumption of HDMTX was tolerated. Methods: Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed. Results: Of 1141 patients who received 4909 courses of HDMTX, 20 patients (1.8{\%} of patients, 0.4{\%} of courses) received 22 doses of glucarpidase. The median glucarpidase dose was 51.6 U/kg (range, 13-65.6 U/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 μM (range, 1.3-590.6 μM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244-763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66-268 hours) for the next HDMTX course, and 72 hours (range, 42-116 hours) for subsequent courses. The median peak serum creatinine level during these HDMTX courses was 2.2 mg/dL (range, 0.8-9.6 mg/dL), 0.8 mg/dL (range, 0.4-1.6 mg/dL), and 0.6 mg/dL (range, 0.4-0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients, and no patient died as a result of methotrexate toxicity. Conclusions: The current results indicated that it is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury.",
author = "Christensen, {Anthony M.} and Pauley, {Jennifer L.} and Molinelli, {Alejandro R.} and Panetta, {John C.} and Ward, {Deborah A.} and Stewart, {Clinton F.} and Hoffman, {James M.} and Scott Howard and Pui, {Ching Hon} and Pappo, {Alberto S.} and Relling, {Mary V.} and Crews, {Kristine R.}",
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AU - Pauley, Jennifer L.

AU - Molinelli, Alejandro R.

AU - Panetta, John C.

AU - Ward, Deborah A.

AU - Stewart, Clinton F.

AU - Hoffman, James M.

AU - Howard, Scott

AU - Pui, Ching Hon

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AU - Relling, Mary V.

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N2 - Background: High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. The authors retrospectively reviewed glucarpidase use in pediatric cancer patients at their institution and evaluated whether subsequent resumption of HDMTX was tolerated. Methods: Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed. Results: Of 1141 patients who received 4909 courses of HDMTX, 20 patients (1.8% of patients, 0.4% of courses) received 22 doses of glucarpidase. The median glucarpidase dose was 51.6 U/kg (range, 13-65.6 U/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 μM (range, 1.3-590.6 μM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244-763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66-268 hours) for the next HDMTX course, and 72 hours (range, 42-116 hours) for subsequent courses. The median peak serum creatinine level during these HDMTX courses was 2.2 mg/dL (range, 0.8-9.6 mg/dL), 0.8 mg/dL (range, 0.4-1.6 mg/dL), and 0.6 mg/dL (range, 0.4-0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients, and no patient died as a result of methotrexate toxicity. Conclusions: The current results indicated that it is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury.

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