CRANIAL IRRADIATION AND PERMEABILITY OF BLOOD-BRAIN-BARRIER TO CYTOSINE-ARABINOSIDE IN CHILDREN WITH ACUTE-LEUKEMIA

Cranial irradiation (CI) is an effective way to prevent central nervou s system (CNS) leukemia in children with acute leukemia (AL), However, it is still unclear whether the antileukemic effect of CI is mediated by alteration of blood-brain barrier (BBB) permeability and consequen t increased levels of systemically administered drugs or whether it si mply results from a direct cytolytic effect on leukemic cells in the m eninges at diagnosis, We evaluated the influence of CI on BBB permeabi lity to 1-beta-D-arabinofuranosylcytosine (ara-C) in 23 children with AL undergoing CI for CNS leukemia prophylaxis. CI was administered at 18 Gy (16 patients) and 24 Gy (7 patients), ara-C Bevels were measured in cerebrospinal fluid (CSF) and plasma before, during, and after CI, Two doses were evaluated: 75 mg/m(2)/day (12 patients) and 480 mg/m(2 )/day (11 patients), CSF and plasma ara-C levels were measured when st eady state was achieved. CSF:plasma ratios, obtained before, during, a nd after CI, were compared by an ANOVA model for repeated measures and by Tukey's test, At the 75-mg/m(2)/day dose, the mean values of ara-C CSF:plasma ratios before, during, and after CI were 0.20, 0.27, and 0 .27, respectively, At the 480-mg/m(2)/day dose, the mean CSF:plasma ra tios before, during, and after CI were 0.09, 0.12, and 0.13, respectiv ely, No significant differences were observed when CSF:plasma ratios w ere compared before and during, during and after, and before and after CI, Our results indicate that CI at the doses used for CNS prophylaxi s in AL does not significantly alter the BBB as far as ara-C is concer ned.