How to monitor MTX dosage in pediatric patients with ALL



To this day, repeated intrathecal injections of high-dose methotrexate (HD-MTX) have been recognized as an option for the prevention of central nervous system damage and as an important option for the treatment of childhood acute lymphoblastic leukemia (ALL)[1]. However, especially in developing countries, the use of high-dose HD-MTX regimens in pediatric cancer patients has been controversial and represents a dilemma that is difficult to balance effectiveness and toxicity. Pediatric patients with cancer in Indonesia face the same dilemma. Due to frequent treatment interruptions and inadequate medical care, clinicians are often reluctant to use HD-MTX therapy, fearing that patients may develop comorbidities such as infections and malnutrition.

The protocol of HD-MTX has been in place for more than 15 years and the dose has been changed, from 500 mg/m2 in 2006, to 1000 mg/m2However, most of the studies have focused on the injection regimen of HD-MTX and little attention has been paid to the toxicity and therapeutic efficacy aspects of this method. Therefore, it is necessary to conduct some studies to obtain basic data in order to improve the efficacy and safety of this therapeutic regimen.

Nur Melani Sari's research team evaluated the toxicity and efficacy of HD-MTX by using 24-hour and 48-hour blood levels of MTX[2].


Experimental results

The team recruited 32 patients, all with ALL in the consolidation phase of treatment with HD-MTX. CTCAE criteria were used for clinical toxicity judgments, such as the occurrence of febrile neutropenia which can be graded as grade 3-4. All subjects received 1000 mg/m2 MTX in accordance with the 2013 Indonesian Standards of Practice for ALL. Blood samples were obtained from subjects at 24 and 48 hours post-dose for analyzing the relationship between blood levels and side effects.

Analysis of the results showed a median MTX level of 29.8 ng/mL (0.065 µmol/L) at 24 hours (IQR 8.1-390.6) and a slight decrease in MTX serum levels at 48 hours (median 28.3 ng/mL and 0.062 µmol/L). The two most common toxicities in patients were hepatotoxicity, 32.2%, and neutropenia, 30.9%. Nephrotoxicity and febrile neutropenia occurred in 8.8% and 5.8%, respectively, with lower rates of mucositis and thrombocytopenia, 4.3% and 5.6%, respectively. In correlation analysis, no statistically significant association was found between MTX levels and other clinical toxicities, except for hepatotoxicity.



From the analysis of the results of this study, it can be seen that the serum MTX levels at 24 and 48 hours were low, with only a 4.4% probability of achieving grade III/IV hepatotoxicity, and about 26.4% cases of grade III/IV neutropenia. No significant correlation between MTX levels and other clinical toxicities could be observed using this two-point blood concentration measurement, except for the ability to show hepatotoxicity. Suitable observation points for MTX blood concentration need to be further investigated.


1.Mantadakis, E., P.D. Cole, and B.A. Kamen, High-dose methotrexate in acute lymphoblastic leukemia: where is the evidence for its continued use? Pharmacotherapy, 2005. 25(5): p. 748-55.

2.Sari, N.M., et al., Monitoring Of High-Dose Methotrexate (Mtx)-Related Toxicity and Mtx Levels in Children with Acute Lymphoblastic Leukemia: A Pilot-Study in Indonesia. Asian Pac J Cancer Prev, 2021. 22(7): p. 2025-2031.

How to monitor MTX dosage in pediatric patients with ALL


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How to monitor MTX dosage in pediatric patients with ALL

How to monitor MTX dosage in pediatric patients with ALL

How to monitor MTX dosage in pediatric patients with ALL

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