Remission induction of meningeal leukemia with high-dose intravenous methotrexate.
Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.
D000293:Adolescent; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007263:Infusions, Parenteral; D007945:Leukemia, Lymphoid / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D007958:Leukocyte Count; D008297:Male; D008577:Meningeal Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000134:cerebrospinal fluid; D009503:Neutropenia / Q000139:chemically induced; D012640:Seizures / Q000139:chemically induced; D013280:Stomatitis / Q000139:chemically induced
D008727:Methotrexate