COGNITIVE SEQUELAE OF TREATMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - CRANIAL RADIATION REQUIRES AN ACCOMPLICE

Purpose: We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL), CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy, Patients and Methods: Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests, These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m(2)) or HD-MTX (4 g/m(2)) with leucovorin rescue, Results: There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4), However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001), Conclusion: We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin. (C) 1995 by American Society of Clinical Oncology.