‘Prophylactic’ Treatment of Meningeal Leukemia in Children by Intrathecal Methotrexate

Abstract

The survival period of children suffering from leukemia could be prolonged by using the new antileukemic agents. On the other hand, the frequency of central nervous system involvement as a complication of this disease was very high, i.e. 10 of 19 cases. Six showed signs of meningeal leukemia while they were in hematologic remission and the other 4 were within acute stage. Nine children were given methotrexate intrathecally as a prophylactic measure at the time when diagnosis of leukemia was confirmed, and did not suffer from this complication during follow-up to 6–13 months. From these data we conclude that the regular administration of methotrexate intrathecally to leukemic patients as a prophylactic measure, with routine spinal fluid examinations, is very useful in preventing or in reducing the central nervous system involvement.

Brain lesions following combined treatment with methotrexate and craniospinal irradiation

“…Our findings of large areas of demyelination in the hemispheric white matter consisting of severe microcavitation, reactive gliosis and loss of oligodendrocytes are in agreement with those of other authors [11][12][13][14][15][16][17][18] who defined this encephalopathy as 'subacute MTX leucoencephalopathy'.…”

Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism

“…However, the BBB can be modulated by tumour-secreted signals, as illustrated by Wnt-positive medulloblastoma that has a better response to chemotherapy, as compared to other subtypes of medulloblastoma, due to a disrupted BBB [ 246 ]. To achieve clearance of cancer cells in the CNS, the BBB has to be circumvented either by changing the modality to radiation [ 247 ], intrathecal application of antimetabolites [ 248 , 249 ], or achieving effective antileukemic CNS concentrations using high-dose systemic regimens of methotrexate [ 250 ] or ara-C [ 251 , 252 ], as CNS concentrations of ara-C reach only 40% of plasma concentrations when administered intravenously [ 230 , 253 ].…”