[show abstract][hide abstract] ABSTRACT: Children treated for acute lymphoblastic leukemia (ALL) as High Risk (HR) patients may be more vulnerable to neurocognitive late effects because of the greater intensity of their therapy. We compared neuropsychological outcomes in children treated for Standard Risk (SR) or HR ALL on Dana-Farber Cancer Institute (DFCI) Consortium ALL Protocol 95-01. We also evaluated their performance relative to normative expectations.
Between 1996 and 2000, 498 children with newly diagnosed ALL were treated on Protocol 95-01, 298 of whom were eligible for neuropsychological follow-up. A feature of this protocol was modification of risk group criteria to treat more children as SR rather than HR patients, intended to minimize toxicities. Testing was completed at a median of 5.3 years post-diagnosis for 211 patients (70.8%; ages 6-25 years; 45.5% male; 40% HR), all of whom were in continuous complete remission.
Test scores for both groups were generally at or above normative expectation, with the exception of verbal working memory, processing complex visual information, and parent ratings of metacognitive skills. After adjusting for covariates, the SR group performed better on measures of IQ and academic achievement, working memory and visual learning. Effect sizes, however, were only in the small to moderate range.
HR patients exhibited neuropsychological deficits relative to SR patients, though the differences were modest in degree. Modification of the risk group criteria to treat more children on the SR protocol therefore likely afforded some benefit in terms of neurocognitive late effects.
Pediatric Blood & Cancer 06/2011; 58(5):758-65. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated late neuropsychological toxicity in children treated for standard-risk acute lymphoblastic leukemia (ALL) who were randomly assigned to receive either cranial radiation therapy (CRT) with double intrathecal (IT) chemotherapy or intensive triple IT chemotherapy (no CRT) as CNS-directed therapy.
Between 1996 and 2000, 164 children with standard-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 95-01 were randomly assigned to receive either 18 Gy CRT delivered in twice daily fractions (0.9 [DOSAGE ERROR CORRECTED] Gy) with double IT therapy (methotrexate and cytarabine) or intensive triple IT drug (methotrexate, cytarabine and hydrocortisone) without CRT. Neuropsychological testing was completed at a median 6 years postdiagnosis for 79 children (CRT, n = 39; triple IT, n = 40), all of whom were in continuous complete remission.
Cognitive function for both groups was solidly in the average range, with no consistent group differences in basic cognitive skills. Children treated on the CRT plus double IT arm did, however, exhibit less fluent output and were less effective at modulating their behavior by parent report.
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.
Journal of Clinical Oncology 12/2007; 25(31):4914-21. · 18.04 Impact Factor