Chemotherapy and attentional dysfunction in survivors of childhood acute lymphoblastic leukemia: effect of treatment intensity.
BACKGROUND
Central nervous system (CNS) directed chemotherapy is replacing prophylactic cranial irradiation in treatment protocols for childhood acute lymphoblastic leukemia (ALL), mainly to reduce long-term neuropsychological sequelae. We evaluated the effects of chemotherapy on attentional function in survivors of ALL and examined whether possible deficits are related to treatment intensity.


METHODS
In a multi-center study, we compared attentional function in 36 children at least 1 year after finishing treatment with chemotherapy only for ALL, with a cancer control group consisting of 39 Wilms tumor patients and with 110 healthy children. We differentiated between standard- and intensified ALL treatment. The role of previously reported risk factors for neuropsychological deficits was also assessed.


RESULTS
After chemotherapy, attentional deficits were detected in patients with ALL, but not in Wilms tumor patients. Children treated according to standard ALL protocols performed worse than healthy controls on only 1 of 10 outcome measures (P = 0.004), while those who had received intensified treatment performed worse on four outcome measures (0.0001 < P < 0.004). Higher treatment intensity, young age at diagnosis, and female gender were associated with worse performance.


CONCLUSIONS
CNS-directed chemotherapy, even in the absence of cranial irradiation, is associated with attentional dysfunction in survivors of childhood ALL, particularly in case of intensified treatment protocols. These sequelae stress the importance of reducing doses of neurotoxic chemotherapy as much as possible in the design of future treatment protocols for ALL.
Buizer
Annemieke I
AI
Department of Pediatrics, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. ai.buizer@vumc.nl
de Sonneville
Leo M J
LM
van den Heuvel-Eibrink
Marry M
MM
Veerman
Anjo J P
AJ
D000293:Adolescent; D017677:Age Distribution; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001288:Attention; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012044:Regression Analysis; D012307:Risk Factors; D017678:Sex Distribution
D000970:Antineoplastic Agents