943 CEREBROSPINAL FLUID (CSF) BIOGENIC AMINE METABOLISM IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA (ALL)

Abstract

Clinical, radiologic and pathologic evidence of central nervous system(CNS)injury may be found in children with ALL who have received CNS prophylaxis with intrathecal(IT) methotrexate (MIX) & craniospinal irradiation. It has been suggested that neuronal susceptibility to MIX is due to inhibition of biogenic aminedopamine(D) & serotonin(S)-synthesis by this drug(Ca Treat Rep 62:1999). To test this hypothesis, we measured levels of homovanillic acid(HVA) & 5-hydroxyindoleacetic acid(HIAA), stable acid metabolites of D & S, in weekly sequential CSF's from 30 patients (pts) with ALL examined prospectively(Group 1), & in CSF's from 130 pts in remission. Group I pts, 22 boys & 8 girls, age 2-15, with normal pre-treatment HVA and HIAA, received 8 doses of IT MTX at weekly Intervals. Regression analysis of HVA levels revealed a gradual decline in the first 4 wks(r=-1.4)&, a more pronounced increase in the next 4 wks(r=+6.5)(p=.027, t-test comparison of slopes). Similar trends were observed for HIAA. These changes were independent of age, sex, and CSF protein elevation. In contrast, there was little intra-subject variability in levels in the absence of intensive MTX therapy;60 paired CSF's obtained at 3 mo intervals, showed no changes in HVA & HIAA. The data provide evidence for MTX induced alterations in biogenic amlne synthesis and/or transport. If the levels reflect altered neuronal activity, these observations may contribute to an understanding of changes in mood, appetite, sleep, & other aspects of behavior which are disrupted during treatment.

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