Effects of different forms of central nervous system prophylaxis on neuropsychologic function in childhood leukemia.

Abstract

A comparison of the late effects on intellectual and neuropsychologic function of three different CNS "prophylaxis" regimens was conducted in 104 patients treated for childhood acute lymphocytic leukemia. Of the children studied, 33 were randomized to treatment with intrathecal (IT) methotrexate alone, 36 to IT methotrexate plus 2,400 rad cranial irradiation, and 35 to IT methotrexate plus intravenous intermediate dose methotrexate. All patients were in their first (complete) continuous remission, were a minimum of one year post-CNS prophylaxis and had no evidence of CNS disease at the time of evaluation. In contrast to the other two treatment groups, children whose CNS prophylaxis included cranial irradiation attained significantly lower mean Full Scale IQs (P less than .001), performed more poorly on the Wide Range Achievement Test, a measure of school abilities, and exhibited a greater number of difficulties on a variety of other neuropsychologic measures. The poorer performance of the irradiated group was independent of sex of the patient, time since treatment and age at diagnosis. These data suggest that the addition of 2,400 rad cranial irradiation to CNS prophylaxis in ALL puts these children at greater risk for mild global loss in intellectual and neuropsychologic ability.

Quantitative morphologic evaluation of magnetic resonance imaging during and after treatment of childhood leukemia

“…However, interpreting the results of clinical studies is complicated by the variation in systemic MTX exposure [14,16,[28][29][30]. Acute events associated with IV-MTX, with or without irradiation, include seizures and transient neurologic abnormalities such as focal sensorimotor deficits, and acute mental status changes occur in 5% to 10% of patients [31][32][33][34][35]. In the large Pediatric Oncology Group (POG) 9005 study approximately 8% of patients experienced acute clinical neurotoxicity after IV-MTX treatment alone; 75% of those patients with symptoms of neurotoxicity had qualitative MR imaging evidence consistent with a diagnosis of LE [27].…”

“…Subtle cognitive deficits have been observed in as many as 60% of patients with ALL and are one of the most serious long-term adverse effects associated with MTX therapy [13,25,26,31,85,86]. Children treated for ALL with moderate-dose IV-or IT-MTX have shown declines in IQ scores comparable to those seen in children treated with low-dose cranial irradiation [17].…”

Neuropsychological outcome in very young hematopoietic SCT recipients in relation to pretransplant conditioning

“…Functions intrinsic to the nondominant hemisphere appear to be most affected. [4][5][6] It has been suggested that diffuse white matter pathology, caused by the neurotoxic treatment agents, may be the primary mechanism underlying the observed functional deficits. [7][8][9] CNS preventive therapy remains an important measure in the treatment of childhood ALL, but cranial irradiation is avoided today and is used only with patients with poor prognosis and under conditions of a CNS relapse.…”

Neuropsychological evaluation of children with intracranial tumors: Impact of treatment modalities

“…In this type of condition the deterioration of cognitive functions can only be attributed to the iatrogenic effect of the treatment [10][11][12][13][14][15]. These studies, however, have one principal drawback: all the patients receive the same total dose (1,800 or 2,400 cGy), which is relatively low compared to that usually used in the treatment of ICT.…”