NEUROCOGNITIVE FUNCTION IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIAACCORDING TO CENTRAL-NERVOUS-SYSTEM TREATMENT TYPE AND AGE

The recognition of neurocognitive late effects, including decline of i ntellect, that can occur after central nervous system (CNS) directed t herapy for childhood acute lymphoblastic leukemia (ALL), has stimulate d research into treatments that retain therapeutic effectiveness but h ave reduced associated neurotoxicity. In this study we compared the ef fects of cranial radiation and high-dose (HD) methotrexate (MTX) on ne urocognitive function of children with ALL. We also sought to determin e whether younger (<3 years) and older (greater than or equal to 3 yea rs) children were differentially vulnerable to HD MTX administered in association with intrathecal (i.t.) cytarabine, prednisone and MTX (tr iple i.t. therapy). Patients were enrolled from two consecutive genera tions in terms of treatment protocols. Group A consisted of 22 childre n who, as part of CNS directed therapy, received cranial radiotherapy (1,800 Gy) plus six i.t. doses of MTX. Group B consisted of 24 childre n who, as part of CNS directed treatment, received 4 intravenous doses of HD MTX (5 g/m(2)) plus 20 doses of triple i.t. therapy. The method of assessment included the application of the age-appropriate Italian version of Wechsler Intelligence Scale for Children-Revised, a measur e of performance, verbal and full-scale IQ. Multiple regression analys is of the group as a whole revealed no significant correlation of full -scale IQ with sex, the natural logarithm of age at the time of diagno sis, age at the time of IQ testing, interval between diagnosis and IQ testing and randomization group (high versus standard doses of L-aspar aginase for group B). Statistically significant differences were obser ved in full-scale IQ (p = 0.002), performance IQ (p = 0.015) and verba l IQ (p = 0.006) between the two groups of treatment (irradiated versu s nonirradiated). The analysis of subgroups by age revealed that diffe rences observed in verbal, performance and full scale-IQ were found ex clusively in children > years of age, whereas no differences were dete cted between irradiated and nonirradiated children less than or equal to 3 years. According to our data HD MTX may be the treatment of choic e for CNS directed therapy in infants and young children with ALL. It remains unclear whether or not reduction or elimination of cranial irr adiation and intensification of parenteral therapy with MTX is advanta geous in children than less than or equal to 3 years of age.