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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Silverstein, F., Hutchinson, R. & Johnston, M. 943 CEREBROSPINAL FLUID (CSF) BIOGENIC AMINE METABOLISM IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA (ALL). Pediatr Res 19, 268 (1985). https://doi.org/10.1203/00006450-198504000-00973
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DOI: https://doi.org/10.1203/00006450-198504000-00973