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Standard IQ tests were performed in 70 children and adolescents 3.5-10 years (median 5 yrs) after 24 Gy cranial irradiation, with or without concurrent intrathecal methotrexate, for central nervous system prophylaxis of acute lymphoblastic leukemia. Lower IQ scores correlated with younger age, female gender, and concomitant intrathecal methotrexate therapy. Multivariate analysis identified age as the most important determinant of the three factors. The lowest IQ scores were observed in girls who were less than 5 years old at the time of irradiation and who received concurrent intrathecal methotrexate. The observed adverse contribution of simultaneous intrathecal methotrexate therapy on IQ outcome may have significant implications for school performance, peer relationships, and occupational expectations.

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