Cerebrospinal fluid and plasma methotrexate levels following high-dose regimen given as a 3-hour intravenous infusion in children with nonHodgkin's lymphoma.

In the French nonHodgkin's lymphoma protocols, central nervous system prophylaxis is provided by high-dose methotrexate (HD-MTX), given as a 3-hour IV infusion of 3 g/m2 MTX along with intrathecal MTX injection. The incidence of CNS relapse is less than 3%. We designed a study to evaluate the MTX transfer across the blood brain barrier in terms of cytotoxic concentrations, during these short-term infusions. Cerebrospinal fluid and plasma MTX levels were measured during 61 courses in 29 children with nonHodgkin's lymphoma; none of them had central nervous system disease. Samples were obtained either 4, 12, 18, or 24 hours after the start of HD-MTX IV infusion. A potentially cytotoxic MTX level (10(-6)M) was reached in all courses at 4 hours (median: 2.3 X 10(-6)M) and remained available in 8/16 courses at 12 hours (median: 1.0 X 10(-6)M) and in only 2/17 courses at 18 hours (median: 0.29 X 10(-6)M). Twenty-four hours after the start of HD-MTX IV infusion, CSF MTX level was always less than 10(-6)M. The plasma MTX levels were 260, 1.3, 1.0, and 1.7 X 10(-6)M at 4, 12, 18, and 24 hours, respectively. There was no correlation between plasma and CSF MTX levels. These data show that potentially cytotoxic MTX concentrations can be reached in CSF after a 3-hour IV infusion of 3 g/m2 in every patient and remain available for at least 8 hours in half of them.