Summary The potential long-term toxicity of central nervous system prophylaxis (CNS-P) in adult acute lymphoblastic leukaemia (ALL, n = 17) and non-Hodgkin's lymphoma (NHL, n = 7) was investigated in a multidisciplinary study. At least 4 years had elapsed from CNS-P (mean 11.5 years) for all patients. Neurological history and physical examination were unremarkable; minor signs were commoner in older patients (P< 0.02). Psychometry yielded normal results, but individual verbal IQ generally exceeded performance IQ, with a trend to more marked differences in younger adults (P = 0.06). EEG was scored and differed significantly from that of controls, with a tendency to more marked (but still minor) abnormalities in younger patients (P = 0.06). Brainstem auditory evoked potentials demonstrated significant but generally minor abnormality in 24% of patients. CT brain scan revealed widening of cerebral hemisphere sulci to >3 mm in 38% of patients; cerebral atrophy was commoner in the older group (P< 0.02) and those with neurological signs (P<0.02). MRI brain scans were normal in all patients tested. Thus, following standard CNS-P for ALL at this hospital, there is a 5% primary CNS relapse rate, and only minimal, mainly subclinical, long-term neuropsychological toxicity.An important aspect of the 'total therapy' concept for treatment of childhood acute lymphoblastic leukaemia (ALL) is the specific prophylactic treatment of the central nervous system (CNS-P) (Aur et al., 1971; Report to the Medical Research Council, 1973). The combination of external cranial irradiation to 24 Gy with five doses of intrathecal methotrexate has reduced the primary CNS relapse rate from about 75% to 10% or less. In the late 1970s reports emerged indicating that long-term survivors of childhood ALL appeared to have subnormal IQ, typically presenting with learning difficulties (Meadows et al., 1981; Eiser et al., 1978;Moss et al., 1981;Carli et al., 1985). It is now apparent that long-term CNS problems may range in severity from minor intellectual dysfunction to severe neuropsychological damage, seizures and dementia (Bleyer, 1981).As ALL is less common in adults than in children, the former have received less attention regarding the potential neurotoxicity of CNS-P. Intensive therapy of adult ALL may now yield survival figures approaching those for children (Linker et al., 1987;Omura et al., 1980). It is therefore increasingly important to look for possible long-term adverse effects of therapy. To our knowledge there are no published data addressing this issue. The results of a multidisciplinary investigation of adults with ALL and NHL who received standard CNS-P are presented.
Materials and methods
PatientsAcute tymphoblastic leukaemia Between 1972 and 1982, 112 consecutive, previously (Lister et al., 1978). In 1986, 12 patients were alive; seven were available for study. Two patients were lost to follow-up, one patient refused to be studied, and two patients were excluded due to a past history of encephalitis and meningitis respectively...
