Some aspects of neurotoxicity associated with central nervous system prophylaxis in childhood leukemia

Late effects of central nervous system (CNS) prophylaxis with cranial radiation (CR) and intrathecal chemotherapy encompass a broad spectrum of phenomena, ranging from fatal leukoencephalopathy to subclinical dysfunctions. Therefore, we studied 55 asymptomatic children with leukemia or solid tumors by means of visual-evoked potentials (VEP) in order to detect subclinical demyelination of the optic pathway after CNS prophylaxis. Ten of the 11 patients showed increased VEP latency after CR with 1,800 cGy, as compared with previous values. One third of our 34 children treated months to years before the study, with 2,400 cGy CR also showed increased VEP latency which was normal in children treated with intrathecal methotrexate only. Growth hormone secretion was investigated using sequential arginine (ARG) and insulin (INS) tolerance tests in 7 leukemic children treated with 1,800 cGy CR. At diagnosis all patients were responsive to both tests; after CNS prophylaxis, 2 patients were still responsive to ARG and INS, whereas the other 5 were responsive to ARG test only. These results are at variance with our previous experience in a series of 22 children treated with 2,400 cGy CR where 2 patients responded to ARG only and 5 did not respond to either stimulus. These data indicate that, even after a reduction of the CR dose, CNS prophylaxis is still associated with subclinical dysfunctions.