Pediatrics · Hematology · 2 h ago
Serum Methotrexate Levels After Intrathecal Treatment in Childhood ALL
A prospective pharmacokinetic study measured serum methotrexate after 124 intrathecal doses in 44 children with acute lymphoblastic leukaemia. Concentrations fell rapidly, and were not associated with methotrexate-related neurotoxicity; the measurements may help interpret unexpectedly elevated levels after suspected overdose or medication error.
- Study included 44 children and 124 intrathecal doses.
- Most 48-hour samples were below quantification limits.
- Serum concentrations were not associated with neurotoxicity.
- Reference values may help assess suspected dosing errors.
Researchers prospectively assessed serum methotrexate (MTX) pharmacokinetics after 124 intrathecal doses in 44 children with acute lymphoblastic leukaemia treated on contemporary protocols. Serum concentrations were measured 2–4, 24 and 48 hours after administration, with the aim of establishing reference values and examining their association with MTX-related neurotoxicity.
Mean concentrations were 0.62 μmol/L at 2–4 hours and 0.057 μmol/L at 24 hours; at 48 hours, 82% of samples were below the assay’s lower limit of quantification. The estimated terminal half-life was 8.3 hours. Neurotoxicity occurred in 7 of 44 patients (16%) and was associated with age 10 years or older, but not with serum MTX concentrations. The study provides reference measurements that may aid interpretation of unexpectedly elevated levels when overdose, medication error or severe toxicity is suspected. The small cohort and absence of an association between concentrations and neurotoxicity limit conclusions about using serum levels to predict toxicity.
In practice
For children with acute lymphoblastic leukaemia receiving intrathecal methotrexate, these prospective measurements provide reference serum concentrations at 2–4, 24 and 48 hours that may help clinicians interpret unexpectedly elevated levels when overdose, medication error or severe toxicity is suspected. The study does not support using serum concentrations to predict methotrexate-related neurotoxicity: events occurred in 7 of 44 patients and were not associated with measured levels. The cohort was small, so the findings are reference data rather than a validated toxicity threshold or a basis for changing routine monitoring.
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British Journal of Haematology: Prospective evaluation of serum methotrexate pharmacokinetics following intrathecal methotrexate in acute lymphoblastic leukaemia ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.