Oral mucositis and salivary methotrexate concentration in intermediate-dose methotrexate therapy for children with acute lymphoblastic leukemia.

The relationship between salivary methotrexate (MTX) concentration and severity of oral mucositis after administration of MTX was investigated in six children with acute lymphoblastic leukemia. They received two administrations of MTX at 500 mg/m2 with one third given bolusly and the remainder by 24-hour continuous infusion. No significant difference among patients or administration session was observed in serum MTX concentration. Detectable concentrations of salivary MTX (greater than 0.01 microM) were observed during nine of the ten infusions. A concentration of 0.1 microM or more, apparently lasting at least 12 hours, was observed during one infusion and followed by severe mucositis. During two of the ten infusions for different patients, concentrations of 0.04 to 0.07 microM and 0.02 to 0.04 microM, apparently lasting at least 12 and 18 hours, respectively, were observed, followed by moderate mucositis. During the other seven infusions, either much shorter or no increase in salivary MTX concentration was observed, with only mild or no subsequent mucositis. Analysis by Kendall's rank method showed a statistical correlation between concentration at 6 hours of infusion and severity of oral mucositis. The findings suggest that the early secretion of MTX into saliva has a significant role in the development of oral mucositis in leukemic children.