This randomized trial revealed only subtle differences 6 years after diagnosis between children who received CNS therapy as CRT plus double IT drug or as intensive triple IT drug. In most situations where comparable therapeutic efficacy can be achieved without CRT, it is preferable to do so. Where therapeutically necessary, however, CRT at lower doses may not add risk for significant neurotoxicity.

Background Dexamethasone is more efficacious than prednisone in the treatment of acute lymphoblastic leukemia (ALL), but has also been associated with greater toxicity. We compared neuropsychological outcomes for patients treated on DFCI ALL Consortium Protocol 00-01, which included a randomized comparison of the two steroid preparations during post-induction therapy in children and adolescents with ALL. Procedure Between 2000 and 2005, 408 children with standard-risk or high-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 00-01 were randomly assigned to prednisone or dexamethasone administered as 5-day pulses every 3 weeks for 2 years, beginning at week 7 of treatment. Blinded neuropsychological testing was completed for 170 randomized patients (prednisone, N = 76; dexamethasone, N = 94), all of whom were in continuous complete remission after completion of therapy. Results Outcomes were comparable for most variables, although patients on the dexamethasone arm performed more poorly on a measure of fluid reasoning (P = 0.02). They also tended to be more likely to be enrolled in special education (dexamethasone, 33% vs. prednisone, 20%, P = 0.09). Conclusions Dexamethasone has well documented benefit in treatment of ALL. Although formal testing provided little indication of increased risk for neurotoxicity relative to prednisone, the somewhat greater utilization of special education services by patients treated with dexamethasone merits further investigation.

Patients with DS treated for AML may have specific post-treatment morbidity in verbal function, whereas those treated for ALL have broader morbidity affecting multiple neuropsychological domains and overall adaptive function. We hypothesize that the broader impairment profile of ALL survivors may be related to a combination of the longer duration of central nervous system-directed treatment for ALL compared to AML and the concomitant limited access to intervention opportunities during active treatment.