TY - JOUR
T1 - Cerebrospinal fluid and plasma methotrexate levels following high-dose regimen given as a 3-hour intravenous infusion in children with nonhodgkin's lymphoma
AU - Vassal, G.
AU - Valteau, D.
AU - Bonnay, M.
AU - Patte, C.
AU - Aubier, F.
AU - Lemerle, J.
PY - 1990/1/1
Y1 - 1990/1/1
N2 - In the French non Hodgkin'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 non Hodgkin'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 × 10-6 M) and remained available in 8/16 courses at 12 hours (median: 1.0 × 10-6 M) and in only 2/17 courses at 18 hours (median: 0.29 × 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 × 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.
AB - In the French non Hodgkin'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 non Hodgkin'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 × 10-6 M) and remained available in 8/16 courses at 12 hours (median: 1.0 × 10-6 M) and in only 2/17 courses at 18 hours (median: 0.29 × 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 × 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.
KW - Cerebrospinal fluid
KW - Methotrexate
KW - Non Hodgkin's lymphoma
UR - http://www.scopus.com/inward/record.url?scp=0025181536&partnerID=8YFLogxK
U2 - 10.3109/08880019009034320
DO - 10.3109/08880019009034320
M3 - Article
C2 - 2397170
AN - SCOPUS:0025181536
SN - 0888-0018
VL - 7
SP - 71
EP - 77
JO - Pediatric Hematology and Oncology
JF - Pediatric Hematology and Oncology
IS - 1
ER -