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

Purpose: We evaluated cognitive sequelae of treatment for childhood ac ute lymphoblastic leukemia (ALL), CNS therapy consisted of cranial irr adiation (CRT) or no radiation. Children were also randomized to singl e intravenous high-dose methotrexate (HD-MTX) or conventional-dose met hotrexate (CD-MTX) during induction, and all patients received intrath ecal (IT) and systemic continuation chemotherapy, Patients and Methods : Sixty-six patients treated for ALL on Dana-Farber Cancer Institute p rotocol 87-01 were evaluated by standardized cognitive and achievement tests, These children had been assigned at diagnosis to a standard-ri sk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, resp ectively. 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 le ucovorin rescue, Results: There was no difference in cognitive outcome s between radiated and unirradiated patients (P > .4), However, the HD -MTX/CRT combination was associated with decreased intelligence quotie nt (IQ estimate, 9.3 points) for girls only (P < .08). A specific defi cit 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 duri ng induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding w as 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.