High Dose Methotrexate in Children with Cancer Without Drug Level Monitoring – 133 Cycles Experience

Abstract

Two years data from children receiving HDM were collected (Jun 2019 – June 2021). Diagnosis, baseline blood parameters were recorded. Alkaline hyperhydration was done overnight; subsequently intrathecal methotrexate followed by intravenous (IV) methotrexate (2–5 g/m2) was given over 24 h. Post chemotherapy alkaline hyperhydration was continued. Urine output and serum creatinine level were monitored. Serum MTX level was not monitored. Leucovorin (15 mg/m2) was given intravenously for six doses (start at 42 h from initiation of HDM). There were 133 cycles administered in 35 children (age range 1–14 years and M:F = 17:18). Underlying diagnosis include B-ALL (28), T-ALL (4), Lymphoblastic lymphoma (2) and medulloblastoma (1). All cycles were administered using peripheral IV cannula. With overnight hydration, target urine pH ≥ 7 was reached in 95/133 (71%). Rapid correction of IV NaHCO3 was given in rest. Median dose of IV methotrexate was 4 g/m2. Children were discharged within four days in 90% of cycles. Notable adverse events were seen in 45/133 (34%) cycles. These include excess vomiting (19), fever (15), gastroenteritis (8), oral mucositis (6), transient SGPT elevation > 5 times normal (3), head ache (3), delayed transient asymptomatic elevation in serum creatinine (3), culture positive sepsis (2), allergic rash over eyelids and scalp (1), acute kidney injury - AKI (1). AKI (oliguric) occurred in a three years old girl who had high-grade fever and diarrhea on third day of HDM, which completely resolved with prolonged hydration and high doses of IV leucovorin along with parenteral antibiotics for sepsis. High dose methotrexate (2–5 g/m2 IV over 24 h) can be administered safely in children with cancer in stable condition without monitoring drug level. Extended alkaline hyperhydration, prompt leucovorin rescue, urine output and serum creatinine monitoring should be followed strictly.