Neuropsychological Outcomes From a Randomized Trial of Triple Intrathecal Chemotherapy Compared With 18 Gy Cranial Radiation As CNS Treatment in Acute Lymphoblastic Leukemia: Findings From Dana-Farber Cancer Institute ALL Consortium Protocol 95-01

Abstract

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.

Neurodevelopmental sequelae of pediatric acute lymphoblastic leukemia and its treatment

“…Even when intelligence in both groups was average, memory or academic achievement was lower in the CR group [Mulhern et al, 1988;Mulhern et al, 1991;Waber et al, 1995;Reddick et al, 2006]. Waber et al [2007] did not find a difference in estimated intelligence between CR and CO groups, but the CR group showed reduced naming speed and parentreport of poorer adaptive skills. However, other studies did not find meaningful differences between CR and CO groups Giralt et al, 1992] and the authors speculate that the agents used, dose, or timing of chemotherapy contributed to their discrepant findings.…”

“…Because children with ALL are treated according to risk-stratified protocols, random assignment is only ethical within risk-stratified cohorts [see MacLean et al, 1995;Waber et al, 2004Waber et al, , 2007. Investigation of the role of demographic variables (e.g., age, sex) on neurocognitive outcomes is complicated by the fact that these same variables are often used in the initial risk stratification and, inevitably, are confounded with treatment.…”

CNS prophylaxis in pediatric acute lymphoblastic leukemia

“…However, CRT is associated with significant side effects, including cognitive, endocrine, and growth dysfunction, as well as secondary malignancies. [2][3][4] Studies have indicated that patients with B-precursor ALL who are CNS1 (Ͻ5 WBC/L and no blasts on cytospin) or CNS2 (Ͻ5 WBC/L and blasts on cytospin) may be successfully treated without CRT. In these trials, CRT is typically replaced with extra doses of intrathecal chemotherapy and/or medium-or high-dose intravenous methotrexate.…”

“…Neuropsychological testing performed 6 years after diagnosis found that cognitive function was in the average range for both patient groups. 2 Historically, T-cell ALL (T-ALL) patients have been considered to be at higher risk of CNS relapse and have received CRT as CNS prophylaxis, but some recent trials have omitted CRT for this patient population.…”

Neuropsychological profile of patients with acute lymphoblastic leukemia.

“…However, studies have been inconsistent with regard to the affected domains and their degree of impairment, especially those that result from intrathecal chemotherapy used to prevent infiltration of neoplastic cells into the CNS. Additionally, few studies have used controlled experimental designs, reflected by the variability of the tests used and the limited availability of tools that evaluate children and the multifactorial aspects of the pathology and modern treatment protocols (Waber et al, 2007).…”