Serum Methotrexate Level and Side Effects of High Dose Methotrexate Infusion in Pediatric Patients with Acute...

Methotrexate (MTX) is an extensively prescribed antimetabolite especially in the treatment of several pediatric cancers, though managing toxicities associated with methotrexate in high dose continues to be a challenge. A prospective study was carried out from April 2017 to October 2018. Children of either sex below 18 years at the time of enrolment and receiving high dose Methotrexate intravenous infusion over 24 h as a 2 g/m², 3 g/m² and 5 g/m² dose was included in the study. The serum methotrexate level was estimated after the start of 48 h HDMTX infusion by using the ARCHITECT methotrexate assay. Toxicity due to HDMTX was assessed by Common Terminology Criteria for Adverse Events v.5.0. A total of 244 HDMTX infusions were delivered to 62 ALL patients. From the total of 244 cycles, serum methotrexate level in 35 cycles after the start of 48 h HDMTX infusion was found to be ≥ 1.0 μmol/L with reported toxicities among 31 cycles (88.6%). In 209 cycles MTX level was found to be less than 1.0 is statistically significant as compared to other cycles (p < 0.0001). Highest toxicities reported were in cycle I (38.8%). The toxicities such as oral mucositis, neutropenia, the elevation of liver enzymes, dermatological toxicities were found more in cycles whose methotrexate level are greater than 1.0 μmol/L. Dose reduction, increased the length of stay and treatment delay occurred in patients with severe toxicities. Severe toxicities of methotrexate can be interrelated with serum methotrexate levels at 48 h after the start of HDMTX infusion.