Long-term cognitive outcome, brain computed tomography scan, and magnetic resonance imaging in children cured for acute lymphoblastic leukemia.
BACKGROUND
Prevention of meningeal recurrence achieved by intrathecal methotrexate (MTX) and systemic chemotherapy is part of standard acute lymphoblastic leukemia (ALL) treatment. Cranial irradiation has been a routine part of past protocol treatment but is currently reserved only for select subsets of patients. Central nervous system (CNS) prophylaxis may cause brain abnormalities such as intracerebral calcifications, cerebral atrophy, and white matter alterations. In addition, long-term neuropsychologic sequelae following CNS prophylaxis have been investigated marginally in children cured for ALL.


METHODS
To explore possible correlations between neuroimaging findings and neuropsychologic outcome, we used detailed cognitive tests to evaluate 21 children with ALL who received cranial irradiation (range, 18-24 Gy) plus intrathecal MTX as CNS prophylaxis. All children were followed prospectively once a year by cerebral computed tomographic scan and magnetic resonance imaging. All patients had continuous complete disease remission for at least 4 years and cognitive tests were performed after neuroradiologic examinations.


RESULTS
White matter abnormalities were associated with poor performance only in a task exploring visual motor integration in about 50% of patients. Intracerebral calcifications correlate with the number of intrathecal MTX doses and with low scores in total intellectual quotient, performance intellectual quotient, and significant impairment in attention and visual motor integration tests. Girls are more vulnerable to the effects of CNS prophylaxis, whereas age at treatment and radiotherapy dose are not relevant to neuropsychologic outcome.


CONCLUSIONS
Our results indicate the need for careful follow-up of children's cognitive abilities because global intellectual measures often fail to detect specific disorders that may cause learning difficulties. Moreover, as the clinical implications of neuroimaging findings are often limited, periodic extensive evaluation by specific neurocognitive tests of mental abilities is recommended to detect early signs of cognitive impairment.
Iuvone
Laura
L
Department of Pediatric Neuropsychiatry, Catholic University of Rome, Rome, Italy.
Mariotti
Paolo
P
Colosimo
Cesare
C
Guzzetta
Francesco
F
Ruggiero
Antonio
A
Riccardi
Riccardo
R
D019072:Antibiotic Prophylaxis; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D001284:Atrophy; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D001932:Brain Neoplasms / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011832:Radiation Injuries / Q000175:diagnosis*; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate